Research centre

Computational models of genotype-phenotype maps, fitness landscapes and evolution

https://www.crg.eu/en/content/research/barcelona-collaboratorium-independent-fellow/nora-martin

The group’s objective is to enhance our quantitative understanding of a phenomenon, which is ubiquitous in the natural world: biological evolution. Quantitative models of evolution have to consist of (at least) two components: variation through random mutation and natural selection. To model the first component, we must examine how random mutations in biological sequences give rise to higher-order molecular and phenotypic changes, which selection then acts on. As an example, let us consider the effects of random RNA sequence mutations on folded RNA secondary structures: we can start with one specific sequence and analyse, how its secondary structure changes after one specific mutation. However, sequences change during evolutionary processes, and so one important challenge is to gain a more general quantitative overview that describes the effects of an arbitrary mutation on an arbitrary sequence. This can be achieved with concepts from the fields of genotype-phenotype (GP) maps and fitness landscapes. These concepts are sufficiently abstract that they are not only useful for the example of RNA, but also for other molecular structures and for phenotypic changes beyond the molecular scale. With this approach, we can gain a better quantitative understanding of variation, and investigate the interplay between variation and selection in evolutionary processes.
This will be a computational/theoretical project, and thus offers an opportunity for students with a highly quantitative background (physics, mathematics etc.) and some programming experience (ideally Python) to apply their skills to exciting biological questions. The student will develop their skills in planning, writing and analysing computer simulations, and gain expertise on the topics of genotype-phenotype maps, fitness landscapes and evolutionary processes.

https://www.crg.eu/en/programmes-groups/al-jord-lab

The Dierssen and the Al Jord labs are collaborating in a quest to understand how Down Syndrome (DS) impacts multiciliated cells, which are vital for human brain, respiratory, and reproductive health. We suspect that they are dysfunctional in DS, and that this may contribute to multisystemic disease aggravation.

Using an interdisciplinary methodology, the student will explore how brain multiciliated cells in a DS model develop both in vivo and in vitro. A key research focus will be to document, with state-of-the-art tools, the obscure mechanical relation between the cytoskeleton and nuclear biomolecular condensates in control and DS mouse brain multiciliated cells. Our toolbox includes techniques like brain dissections, primary neural stem cell cultures, protein multiplexing, advanced live and super-resolution imaging, spatial transcriptomics, and force measurement and modulation assays.

Objectives:
1. Investigate the role of multiciliated cells in Down syndrome: Characterize the structure and function of multiciliated cells in DS models, aiming to understand how DS affects these cells in the brain ventricles and contributes to neurodevelopmental phenotypes.

2. Elucidate the cytoskeletal and nuclear dynamics in DS multiciliated cells: Explore the mechanical relationship between the cytoskeleton and nuclear biomolecular condensates in multiciliated cells of DS models using advanced imaging and molecular techniques, to uncover potential pathways of dysfunction specific to DS.
We are looking for a student with a background in Neurobiology, Cell Biology, Molecular Biology, or Biophysics, who is interested and excited about the mysteries of DS, aging, cytoskeleton, biomolecular condensates, and mechanobiology as we are.

The scientific aspects of the project will be supervised by Dr. Dierssen and Dr. Al Jord in weekly meetings and day-by-day discussion along with a lab researchers. This will allow to quickly incorporate technical and training aspects necessary for the proper development of the project. The CRG and the Parc de Recerca de Barcelona offer a rich scientific environment with experts in the field of biomedicine. Moreover, the CRG has a training series ("Courses@CRG”).

Down Syndrome, Brain, Mechanobiology, Multiciliated Cells, Cytoskeleton, Biomolecular Condensates

Mechanical force-based control of RNA dynamics in synthetic cell-like compartments

https://www.crg.eu/en/programmes-groups/al-jord-lab

Cytoskeletal forces are fundamental drivers of cellular organization, orchestrating multiple biological processes. While these forces are known to influence nuclear positioning and mechanics, their impact on intra-nuclear dynamics remains largely unexplored. Recent findings from our lab reveal that cytoplasmic forces actively remodel nuclear condensates, critical for RNA processing. Given that biomolecular mobility dictates enzymatic efficiency, we hypothesize that cytoskeletal forces regulate nuclear RNA processing by mechanically agitating the nucleus and dynamically mixing the nucleoplasm.

To test this hypothesis, the student will play a central role in developing a biomimetic system that integrates cytoskeleton-driven agitation of isolated nuclei and synthetic nucleus-like vesicles. Through this project, the student will gain expertise in advanced imaging, biophysical analysis, and synthetic biology approaches, contributing to a deeper understanding of the mechanobiology of nuclear compartmentalization.

Aim 1: Agitate Isolated Nuclei & Nucleus-like Vesicles in Microwells
The student will establish a controlled system where isolated nuclei and lipidic vesicles are subjected to cytoskeleton-driven mechanical forces. Actin and microtubule networks will generate controlled agitation, with its effects assessed via nuclear membrane fluctuations, nuclear condensate diffusion, and the mobility of encapsulated beads within vesicles. These experiments will define the key biophysical parameters governing nuclear agitation.

Aim 2: Reveal Impact of Agitation on RNA Processing Dynamics
To uncover how cytoskeletal forces influence RNA processing, the student will monitor RNA-based reactions in isolated nuclei and vesicles using live fluorescence imaging. By tuning mechanical sensitivity through variations in nuclear rigidity, they will quantify changes in RNA processing kinetics under different cytoskeletal force conditions.

Expected Outcomes
This study will reveal how cytoskeletal forces regulate nuclear RNA processing, offering a paradigm shift in our understanding of mechanical control over nuclear functions. The student’s contributions will be instrumental in generating novel insights into nuclear organization, with implications for fundamental cell biology, disease mechanisms, and RNA-based therapeutics.

Biomimetic systems, Cytoskeletal forces, Mechanobiology, Nuclear condensates, RNA

https://www.crg.eu/ca/programmes-groups/hopfler-lab

In the “Dynamics of protein synthesis & RNA decay” lab we are interested in how cells tune protein production by adjusting the stability of messenger RNAs (mRNAs) to ensure cellular fitness and health. Traditionally, the selective degradation of mRNAs has been attributed to the recognition of nucleotide sequence elements by proteins or small RNAs that subsequently recruit decay factors. In our lab, we investigate a distinct, newly emerging paradigm of gene regulation termed “peptide-mediated mRNA decay” (PMD). In PMD, not the mRNA sequence but rather the nascent protein is recognized to trigger degradation of the encoding mRNA during its translation by the ribosome. This project focusses on the molecular signals that regulate tubulin mRNA degradation by PMD.

Tubulin mRNAs are selectively degraded when cells sense excess free tubulins, the building blocks of the microtubule cytoskeleton. In this case, a recognition factor binds the nascent tubulin protein on the ribosome. Subsequently, an adapter protein and decay factors that execute mRNA degradation are recruited. Perturbed tubulin mRNA turnover results in severe phenotypes, such as cell division defects, impaired neurodevelopment, ciliopathies, and infertility. However, it remains unclear how cells sense free tubulin concentration and accordingly control the activity of tubulin mRNA decay factors. This project will focus on filling this critical knowledge gap by systematically studying the molecular mechanisms that govern the activity of individual tubulin mRNA decay factors. To this end, we will use a combination of biochemical reconstitution approaches, functional cell biological assays, as well as advanced proteomics methods. Results from this work are expected to uncover fundamental principles of tubulin regulation needed for faithful cell division and organismal development.

genome.crg.cat

Understanding Earth’s biodiversity and responsibly administrating its resources is among the top scientific and social challenges of this century. The Earth BioGenome Project (EBP) aims to sequence, catalog and characterize the genomes of all of Earth’s eukaryotic biodiversity over a period of 10 years (https://www.pnas.org/content/115/17/4325). The outcomes of the EBP will inform a broad range of major issues facing humankind, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. It will contribute to our understanding of biology, ecology and evolution, and will facilitate advances in agriculture, medicine and in the industries based on life: it will, among others, help to discover new medicinal resources for human health, enhance control of pandemics, to identify new genetic variants for improving agriculture, and to discover novel biomaterials and new energy sources, among others.
The value of the genome sequence depends largely on the precise identification of genes. The aim of the research project is to contribute to the development of gene annotation pipelines that produces high quality gene annotations that can be efficiently scaled to more than one million species. Our group has a long-standing interest in gene annotation. Roderic Guigo developed one of the first computational methods to predict genes in genomic sequences, which has been widely used to annotate genomes during the past years. On the other hand, we are part of GENCODE, which aims to produce the reference annotation of the human genome. Within GENCODE we have developed experimental protocols to efficiently produce full-length RNA sequences.
Within the framework of this program, there are three possible specific projects
1. Methods for genome annotation based on long read RNAseq (experimental/computational)
2. Methods for selenoprotein prediction and annotation (bioinformatics)
3. Prediction high quality complete annotations (including lncRNAs) using Machine learning (i.e.. structured decoding from learning embedding) and large language models (strongly computational)

Biodiversity Genomics, Gene annotation, Machine Learning, Artificial Inteligence, long-read RNAseq

https://www.crg.eu/en/programmes-groups/tabara-lab

The levels of mtDNA are tissue- and developmental-stage specific and tightly regulated by a controlled balance between replication and degradation. While factors such as ATP demand and nucleotide availability are thought to influence mtDNA content, the precise mechanisms and factors regulating mtDNA copy number remain poorly understood. Importantly, dysregulated mtDNA levels (either increased or decreased) have been linked to a wide spectrum of human diseases, including mitochondrial and metabolic disorders, cancer and neurodegeneration. Therefore, understanding how cells maintain adequate mtDNA levels is critical for elucidating disease mechanisms and developing new therapeutic strategies. In our recent work, we began to shed light on this process by identifying a novel pathway essential for mtDNA degradation. Building on these results, the trainee will continue this line of research by characterising additional factors involved in mtDNA dynamics.

https://www.crg.eu/en/group-members/eric-latorre-crespo

Mutational signatures derived from cancer genomes, catalogued in COSMIC, have become a central tool for diagnosing and interpreting the biological processes active within cancer tissues. Importantly, many mutational signatures have been linked to specific endogenous or exogenous aetiologies, including defects in DNA repair pathways or exposure to mutagens. This association opens up opportunities for personalised medicine, as the presence of particular signatures can reveal exploitable weaknesses or specific vulnerabilities of a cancer tissue that may inform prognosis or therapeutic strategies. In contrast, an equivalent framework for epigenetic alterations (“epimutations”), such as abnormal DNA methylation changes, is still largely unexplored.

This project aims to develop a methodology to infer _epimutational signatures_ by adapting the conceptual and computational framework of COSMIC mutational signatures to epigenomic data. The central goal is to identify recurrent patterns of epimutations across samples using dimensionality reduction techniques and to assess whether such patterns may reflect distinct epigenetic aetiologies.

First, inspired by COSMIC, the project will explore grouping DNA methylation changes at CpG sites according to their local nucleotide sequence context, such as trinucleotide or extended k-mer contexts centered on CpGs. This approach enables the construction of epimutation catalogs that are directly analogous to classical mutational catalogs and may capture sequence-dependent biases in epigenetic instability.

Second, the project will investigate spatially aware dimensionality reduction techniques that explicitly model the structured nature of the epigenome along the genome. In particular, wavelet-based representations will be explored to summarize methylation variation across multiple genomic scales, from local CpG neighborhoods to broader regulatory domains, while preserving spatial correlations.

The student will implement and compare these approaches, derive epimutational signatures using NMF, and evaluate their robustness, interpretability, and potential links to known epigenetic regulatory pathways using public cancer methylation datasets.

https://genome.crg.cat/

We are seeking a motivated Master’s student to join the PyriSentinel team (pyrisentinel.eu), an international collaboration investigating microbial biodiversity in ~300 high-altitude lakes across the Pyrenees. These lakes are extreme ecosystems shaped by geographic isolation, low nutrient availability, high UV radiation, and strong climatic variability.
You will analyze shotgun metagenomic sequencing data (long-read datasets from PacBio) to characterize microbial communities and their genomic diversity across lakes.


Main tasks (adaptable to your interests):
-Process and analyze shotgun metagenomic data (QC, assembly, binning, annotation)
-Compare microbial communities across lakes and environmental gradients (diversity, taxonomy, functional potential)

This project will be carried out at the Centre for Genomic Regulation (CRG, Barcelona), a leading international biomedical research institute. The student will benefit from:
-A highly international environment
-Access to training courses, seminars, and workshops
-Strong computational infrastructure
-A collaborative research culture and opportunities to connect with partners in France and Andorra through the PyriSentinel network

Desired profile:
Interest in bioinformatics, metagenomics, and microbial ecology. Basic familiarity with Linux and/or Python/R.

https://ibecbarcelona.eu/es/bioinspired-interactive-materials-and-protocellular-systems/

César Rodriguez-Emmenegger

The goal of this master thesis is to develop nanocoatings to improve the hemocompatibility by mimicking endothelium.
Natural endothelium, the lining of blood vessel is the only surface that can modulate the state of blood, allowing coagulation when needed, restricting it to a region, but preventing it for causing negative event. Unfortunately, there is no blood-contacting medical device today capable of this. The consequences in blood-contacting medical devices, range from clot formation, clogging pumps, risk of thrombosis or hemorrhage and even much more devastating when dealing with pediatric oxygenators. Our goal is to devise a radically new concept to interface blood, where a synthetic or hybrid nanocoating is capable of mimicking the most salient aspects that make natural endothelium unique (see: 10.1002/mabi.202400152). This master thesis aims at contributing towards this goal. Embedded in a highly interdisciplinary team of chemists, physicists, bioengineers and biologists, the candidate will develop a nanoscale coating having the ability: (1) to be stealth to blood, adding a cloak of invisibility and preventing activation of coagulation and inflammation. (2) locally modulate activation, so that you can stop clot formation right before it accumulates. (3) Interactive, by exploiting mechanism to trigger the fibrinolytic system and or turning platelets quiescent.
The specific goals of this master thesis are:
(1) Synthesis of antifouling polymer brushes and evaluation of stealth performance
(2) Functionalization with coagulation inhibitors and study their capability to inhibit coagulation
(3) Introduce a mini-fibrinolytic and NO-release system
(4) Implement experiments to probe your coatings
This thesis entails training in advanced polymer synthesis, characterization of nanoscale coatings (XPS, SPR, AFM) and characterization of blood-material interactions at our labs (SPR, basic hemocompatibility studies) as well as through our collaborators in University Clinic Aachen, Germany, ISGlobal Barcelona and Institute of Macromolecular Chemistry Prague.

antifouling, polymer brushes, nanotechnology, nanomedicine, hemocompatibility

https://ibecbarcelona.eu/bioinspired-interactive-materials-and-protocellular-systems/

The goal of this master thesis is to synthesize a small library of amphiphilic comb polymers, study their self-assembly into biomembranes and exploit their heterogeneity to achieve cell-mimetic functions.
Bottom-up synthetic biology proposes the creation of life-like synthetic cells from the self-assembly of natural and synthetic components and it holds promise as a platform to understand biology and to design new micromaterials for biomedicine and drug delivery. Arguably, the synthetic cell membrane is one of the most important parts as in the membrane all interactions (sensing, deformation, communication, cell division, etc.) occurs. It necessary to develop new biomimetic vesicles beyond the state-of-the-art liposomes and polymersomes. Our group recently demonstrated that amphiphilic comb polymers consisting of a hydrophilic backbone and hydrophobic side tail assembled into biomimetic vesicles, termed “Combisomes” with superior stability compared to liposomes but that faithfully recapitulate physical properties and dynamics of cell membranes, in spite of their large molecular weight (Wagner, Adv Science, 2022). They could harbor lipids, transmembrane proteins and fuse with cell membranes. Moreover, we elucidated the mechanism of assembly via a combination of biophysical techniques and molecular dynamics simulations. However, how the molecular structure and topology influences the combisome properties remains unexplored but holds promise for the design of precision vesicles.
The specific goals of this thesis are:
(1) Synthesis of backbone of the comb by copolymerization of of N,N-dimethylaminio acrylamide and a betaine-acrylamide with different proportions and degrees of polymerization
(2) Synthesis of supramolecular comb polymers using the backbone from (1) and different hydrophobic ligands including dialkyl phosphates (C8-16) and dendronized ones.
(3) Modelling of how the randomness in the sequence can be exploited to achieve emergent properties such as fusion with cells, or engulfment.
(3) Self-assembly into vesicles and study their main physical properties (thickness, flexibility, stability, lateral mobility).
This thesis will provide training in advanced controlled radical polymerization, molecular self-assembly, optical, electron and force microscopies and biophysical techniques based on them. It will develop completely new vesicles for synthetic biology and nanomedicine.

biomembranes, polymer chemistry, self-assembly, polymersomes, soft-matter microrobots

https://ibecbarcelona.eu/bioinspired-interactive-materials-and-protocellular-systems/

The goal of this master thesis is to study the molecular and structural parameters governing vesicle formation for ionically-linked comb polymers (iCPs) and its exploitation to build synthetic cells capable of engulfing and killing bacteria resistant to antibiotics.
Antibiotics changed medicine and enormously positively affected the quality and extent of life. However, the current state of welfare is threatened by the emergence of bacterial strains resistant to antibiotics (AMR) that claim the lives of millions every year. Furthermore, the development of new antibiotics by pharmaceutical companies has essentially stalled due to economic and regulatory obstacles. Our group is developing a new paradigm to fight AMR using Phagocytic Synthetic Cells (PSCs). The PSCs are a new type of synthetic cells decorated with stickers and antimicrobial components. The stickers bind specifically to epitopes on the surface of a bacterium causing it to be engulfed into an endosome where the antimicrobial components tear the bacterium's membrane, killing it. This mode of action is inspired by phagocytosis. Towards this aim, our group pioneered the development of two new classes of macromolecular amphiphiles: Janus dendrimers (JDs) and iCPs and demonstrated for the first time the engulfment of living bacteria and its killing and currently we are optimizing their use to treat and prevent infections in cystic fibrosis patients.
The specific goals of this master thesis are:
(1) Self-assembly of vesicles from iCPs, with structural variation and correlate this with the membrane thickness, bending rigidity, and overall stability
(2) Study the engulfment of 2 model bacteria
The candidate will be trained in self-assembly, confocal fluorescent microscopy and related techniques (FRAP, FRET, fluctuation analysis), AFM, DLS. Moreover, they will receive training in basic microbiology. This project is additionally supported by an ERC Consolidator

https://ibecbarcelona.eu/bioinspired-interactive-materials-and-protocellular-systems/

Samuel Sanchez Ordoñez

Indisputably, the most fascinating and efficient microrobots capable of moving and performing various tasks are natural cells. By engineering simple cell-mimicking systems often referred to as synthetic cells, we can learn about their natural counterparts and derive design principles of soft-matter microrobots capable of performing cell-like and beyond-nature activities. In this project, we aim at engineering motile synthetic cells which will move by reshaping their cell membrane facilitated by adhered nanomotors. Such type of motion is ubiquitous in cells which exploit appendages or generated protrusions to propel through the surrounding medium. Our goal is to couple force generation at the points of particle attachment, self-organized clustering of these particles, and membrane morphing to generate a feedback loop that will control the motion of this active system. The nanomotors will be integrated either in the lumen or will be decorating the vesicle membrane. They will harvest chemical energy and transform it into forces at the points of contact with the membrane. If these forces are large enough the vesicle will deform during its motion. Thus, the deformation and propulsion become coupled, similar to the motion of cells mediated by the cytoskeleton. This will allow us to study the self-organization of nanomotors at the membrane, potentially resulting in their emergent collective behavior that can amplify propulsion.
This project will encompass three phases: (1) the synthesis of building blocks (vesicle forming amphiphiles, SPP, linkers for the enzymes, etc.) and self-assembly, (2) the design and study of different motion patterns, and (3) the evaluation of emergent behavior such as collective motion or swarming.
The student will be hosted in the groups of Prof. Rodriguez-Emmenegger and Prof. Samuel Sanchez Ordoñez, specialist in synthetic cells and nano/microrobotics

biomembranes, nanomotors, synthetic cells, self-assembly, polymersomes, soft-matter microrobots

https://ibecbarcelona.eu/nanodevices/

3D bioprinting enables the construction of reproducible and scalable tissues which could be capable of imitating the complexity of natural tissue. Despite advancements in bioinks and printing technology, achieving complex skeletal muscle construct shapes with desired myofiber orientation have remained challenging. In the Smart Nano-bio-devices Group at IBEC, we have developed a technique based on 3D bioprinting to control bioengineered skeletal muscle myofiber alignment and orientation (patent application in preparation). The aim of this project is to 3D bioprint skeletal muscle tissue with bioinspired architectures. It is expected to obtain a functional, tridimensional structures made of skeletal muscle tissue with potential applications in biohybrid robotics, tissue engineering and regenerative medicine.

https://ibecbarcelona.eu/integrative/

Biohybrid devices are systems that combine living cells with soft materials to engineer functions that outperform inert machines. One example of this new type of devices is the use of muscle cells to power soft robots that perform functions such as swimming, walking, gripping or pumping. A main goal of our group is the development of a new generation of biohybrid devices based on folded stem cell tissues under optomechanical control. Thanks to the potential of stem cells, these devices will be able to self-heal, to self-assemble, to self-replicate, and to generate significant forces such as those that drive early embryonic development. In this project the student will actively engage in integrating a diverse array of tools spanning experimental bioengineering to computational modeling. On the experimental front, the student will gain hands-on experience with techniques such as micropatterning, microfluidics, and optogenetics. Micropatterning and microfluidics will be employed to sculpt tissues, while optogenetics will enable precise control over tissue movements. Complementing these experimental approaches, the computational facet of the project will involve the use of hierarchical 3D vertex models, facilitating a comprehensive understanding of the dynamics at play. The specific tasks of the project will be discussed and tailored to the student’s background and interests, with the final goal of designing and testing biohybrid soft robots with sensing, actuation and control capabilities.

https://ibecbarcelona.eu/integrative/

Physical forces impact biological function. This is particularly relevant in the intestinal epithelium, the fastest self-renewing tissue in the body. Rapid self-renewal is enabled by stem cells that reside at the bottom of highly curved invaginations called crypts. To maintain homeostasis, stem cells constantly divide, giving rise to new cells that proliferate further, differentiate, and migrate. How the distinct functions involved in intestinal self-renewal are coordinated to ensure homeostasis is poorly understood. In this project we will test the hypothesis that the forces experienced by cell nuclei govern cell division, migration and differentiation. We will test this hypothesis using intestinal organoids as model systems. The MSc student will use technologies developed in our group (Perez-González et al, Nature Cell Biology, 2021) to map cellular and nuclear forces with single cell resolution. We will then study the mechanistic relationship between these forces and the cell division rates and migration velocity. We expect that this project will contribute to explain how physical forces govern tissue homeostasis.

https://ibecbarcelona.eu/nanobioengineering/

Metastasis-on-a-chip platforms enable the study of tumor cell behavior in controlled, human-relevant microenvironments that reproduce key features of metastatic niches. In this project, the student will work with microfluidic and 3D bioengineered platforms designed to model metastasis in pediatric tumors, including neuroblastoma, Ewing sarcoma, and osteosarcoma.

The project focuses on the fabrication and experimental characterization of distinct metastatic niches, such as bone-, lung-, and lymph node–like environments, using defined biomaterials and microfluidic architectures. The student will investigate how different microenvironmental stimuli influence tumor cell migration and metastatic behavior.

The project will also incorporate integrated biosensors to monitor functional cellular responses within the chip, providing quantitative readouts that complement imaging-based analyses.

The student will gain hands-on experience in microfabrication, 3D cell culture, biomaterial-based niche engineering, fluorescence microscopy, sensor-based measurements, and quantitative data analysis. This project is suitable for students with a background in bioengineering, biomedical sciences, chemistry, physics, or related disciplines who are interested in experimental cancer research and advanced in vitro models.

Metastasis-on-a-chip, dvelopmental cancer, tumor microenvironment, bioengineered niches, biosensors

Extracellular vesicle–nanoparticle systems for hyperthermia-based approaches in bioengineered human metastasis models

https://ibecbarcelona.eu/nanobioengineering/

Hyperthermia-based therapies exploit localized heat generated by functional nanoparticles to induce tumor damage and are emerging as promising physical approaches in cancer treatment. In this project, the student will work with extracellular vesicles (EVs) used as biological nanovehicles to transport hyperthermia-inducing nanoparticles in advanced bioengineered human metastasis models relevant to pediatric cancer.
The project will be carried out using a combination of 2D cell cultures, 3D bioengineered matrices, and metastasis-on-a-chip platforms available in the laboratory. The student will study how EV-associated nanoparticles interact with tumor cells within different metastatic niches and how the local microenvironment influences cellular responses to hyperthermia-based stimuli.
A central goal of the project is to evaluate the performance of EV-based nanoparticle systems under conditions relevant to hyperthermia approaches in human-relevant in vitro models. Experimental work will focus on the characterization of EV–nanoparticle constructs, their uptake and spatial distribution within bioengineered tissues, and their effect on tumor cells, combining fluorescence microscopy with quantitative analysis.
Through this project, the student will gain hands-on experience in EV handling, nanoparticle-based systems, bioengineered metastatic niche models, metastasis-on-a-chip platforms, fluorescence microscopy, and quantitative data analysis. This project is suitable for students with a background in biology, biomedical sciences, bioengineering, or related disciplines who are interested in cancer therapies, nanomedicine, and advanced in vitro models.

Hyperthermia, Nanoparticle-based therapies, Extracellular vesicles, Bioengineered metastasis models, Pediatric cancer

https://ibecbarcelona.eu/nanodevices

This project aims to develop biodegradable urease-functionalized nanomotors capable of autonomous motion for improved drug delivery in bladder cancer. The work will focus on optimizing enzymatic propulsion, drug loading, and release kinetics, as well as evaluating the nanomotors’ penetration and retention in relevant biological models. Throughout the project, the student will gain interdisciplinary training bridging chemistry and molecular biology. On the chemistry side, the student will gain experience in the synthesis and functionalization of nanomotors, along with characterization techniques such as fluorescence microscopy, particle tracking analysis, dynamic light scattering (DLS), and electron microscopy (SEM/TEM). In the molecular biology part, the student will assess cellular uptake, biocompatibility, and therapeutic efficacy in 2D and 3D bladder cancer cell lines (e.g., T24, RT4) and patient-derived organoids, using techniques such as confocal microscopy, qPCR, and western blotting. This project offers a unique opportunity to develop skills at the interface of nanotechnology and cancer therapeutics, with direct implications for minimally invasive, highly efficient bladder cancer treatment strategies.

Nanomotors, Enzymatic propulsion, Bladder cancer, Nanoparticles, Advanced Nanotherapeutics

Metabolic Imaging of Hepatoblastoma Using Hyperpolarised Magnetic Resonance

https://ibecbarcelona.eu/es/molecular-imaging-for-precision-medicine/

Hepatoblastoma (HB) is the most common malignant liver tumor in children, with rising incidence in Europe and limited biomarkers for early detection and treatment monitoring. Improving metabolic phenotyping could provide transformative insights into tumour biology and therapeutic response. This project offers Master students the opportunity to contribute to a cutting-edge research programme at the intersection of cancer metabolism, biomedical engineering and magnetic resonance physics.

The project focuses on studying HB metabolism in vitro (2D cell cultures, organoids and microfluidic tumour-on-chip systems) and in vivo (preclinical mouse models) using hyperpolarised magnetic resonance (HP-MR), a technology that increases MR sensitivity by more than 10,000-fold, enabling real-time measurement of metabolic fluxes non-invasively.
Students will investigate metabolic pathways relevant to hepatoblastoma progression, including glycolysis and lactate production using [1-13C]pyruvate and TCA cycle metabolism using [2-13C]pyruvate or [1-13C]acetate, substrates validated in cancer metabolic imaging.

Training and Skills:
– Cell culture, viability assays and metabolic perturbation experiments
– Hyperpolarisation (dissolution-DNP), NMR spectroscopy and HP-MRSI acquisition
– Data analysis and kinetic modelling of metabolic fluxes
– Opportunity to contribute to publications and international collaborations

Candidate Profile:
Students in biomedical sciences, biotechnology, physics, bioengineering, chemistry or related fields, motivated to learn experimental methods and translate research into clinical impact.

https://ibecbarcelona.eu/es/molecular-imaging-for-precision-medicine/

Magnetic resonance spectroscopy (MRS) is a gold-standard tool for non-invasive molecular characterisation. Recent breakthroughs in hyperpolarisation (HP) technologies offer >10,000-fold sensitivity enhancement, enabling real-time metabolic measurements even in microlitre-scale samples. To leverage this potential for disease-on-chip research, scalable engineering solutions are urgently needed.

This Master thesis targets the development, optimisation and validation of a benchtop NMR spectrometer specifically designed to interface with tumour-on-chip and liver-on-chip systems (the only one in the world is in our lab!). Students will participate in multidisciplinary engineering work, including optimisation of RF coil performance, chip geometry and materials, microfluidic circuit design, and acquisition strategies to maximise signal-to-noise ratio and temporal resolution.

Training and Skills: Students will gain hands-on experience in microfabrication, RF engineering, MR pulse programming, LabVIEW/Matlab/Python-based acquisition control, computational modelling and biomedical device validation.

Candidate Profile: Ideal candidates have backgrounds in engineering, physics, electronics, instrumentation or bioengineering, with motivation to translate device prototyping into biomedical impact.

https://ibecbarcelona.eu/research-groups/spatial-biotechnology-group/

Tumors typically harbor diverse populations of genetically distinct cancer cells, or subclones, that coexist with sources of heterogeneity from the tumor microenvironment, such as the presence of stromal and immune cells, hypoxic regions, and areas with unique extracellular matrix components. This complexity confounds accurate cancer diagnosis, treatment selection, and prediction of therapeutic response. Understanding how subclones arise and evolve will help design more effective tumor therapies and diagnostic tools to predict clinical outcomes.

Our group is focused on the development of high-throughput and spatial perturbation technologies and their application to understand how cancer cell clones spatially organize to drive solid tumor development. Some of the questions we are interested in, include:
- How is clonal cooperation established and maintained?
- How does metabolite accessibility regulate growth of neighboring cancer cell clones?
- How do clonal populations and microenvironments evolve in primary tumors?

We seek a motivated student with interest in biomedicine and background in one or more of the following areas: biology, chemistry, biotechnology, mathematics, and/or computer science. The specific aims of the project will be tailored to the student, depending on his/her scientific interests and background, and within the framework of the group. We study clonal behaviors in solid tumors and use samples from clinical sources, murine models, and in vitro tissues. We profile them using various technologies including highly multiplexed tissue imaging (e.g., spatial proteomics, metabolomics, transcriptomics), super-resolution microscopy, mass spectrometry, and multimodal microscopy, genetic and small molecule screens, assay automation strategies, cell engineering approaches, and computational tools for deconstructing spatial patterns. The researcher joining the lab will be trained in basic cancer cell biology, experimental design, data analysis, and oral presentation skills. The student will learn to independently perform highly multiplexed tissue imaging, from the experimental (e.g., sample preparation) and/or the computational side (e.g., spatial data analysis).

https://atto.icfo.eu/

Your aim will be to use bandgap photonics to shape and control the dispersion landscape of an ultrafast and broadband optical pulse to the single-cycle limit as such a pulse will allow generating a single attosecond-duration burst of X-rays. This project reaches the physical limit of pulse generation and requires acquiring a theoretical and experimental understanding of ultrafast optics, laser science, nonlinear physics and bandgap photonics

https://www.icfo.eu/research-group/33/stm/home/437/

We use low-temperature (~350 mK) STM/STS to study the correlated phases that emerge in such two-dimensional and moiré systems. STM accesses atomic and electronic structures simultaneously through topography and local density of states mapping. With such powerful combinations of high spatial and energy resolution we would like, for example, to understand the mechanism behind the superconducting state in magic-angle graphene.

Quantum-to-Sound Lab: Experimental, Computational, and Perceptual Pathways for Sonifying Complex Systems

https://www.icfo.eu/research-group/11/qot/home/437/

This Major Research Project provides a flexible framework for multidisciplinary Master students who wish to explore how sound can be used to investigate, communicate, or artistically engage with complex physical phenomena—with a strong emphasis on rigorous engagement with quantum theory. While student projects may result in artistic outputs (instruments, installations, performances), any artistic direction will be grounded in a serious study of the relevant quantum concepts, developed through regular discussion with the supervising team and supported by the group’s expertise.

Students may choose one (or combine several) of the following directions:

1. Sonification of experimental data: convert real datasets (optics, materials, microscopy, spectroscopy, sensor logs, time series) into sound to reveal patterns, drifts, correlations, or rare events; design mappings grounded in signal processing and perception.

2. Model-based sonification of dynamical systems: sonify simulations of oscillators, waves, networks, stochastic processes, or quantum-inspired dynamics; explore how different representations (time-domain, frequency-domain, phase-space-like views) shape listening outcomes.

3. Interactive audio tools and DSP design: build real-time software instruments/effects where parameters are driven by data or physical models (spectral processing, spatialization, granular/synthesis engines, reverberation and resonance models).

4. Experimental interfaces and prototyping: develop physical or hybrid interfaces (sensors, actuators, mechanical resonators, feedback setups) that couple experimental measurements to sound generation/processing.

Across all routes, students will be supported to: define a research question, select datasets or experimental setups, implement a reproducible pipeline (code + documentation), and evaluate results (technical metrics and/or perceptual/user studies). Outcomes can range from a scientific analysis tool to a creative prototype, but always with publishable-quality methodology and open, reusable deliverables.

livinglight.icfo.eu

Rapid growth and success of personalized medicine will depend on the development of new technologies that target individual disease mechanisms. Often, specific diseases require the targeted activity modulation of a subset of neurons within a neuronal circuit, without affecting neighbouring cells. Neuromodulation using light, through expression of light-gated ion channels (e.g. channelrhodopsin) in neurons bears tremendous promise due to the unprecedented spatiotemporal control over which light can be delivered. In humans, however, this requires surgical implantation of a light-delivery device close to the target cells – a procedure that largely limits the transition of optical neuromodulation techniques from the bench to the bedside. In addition, channelrhodopsin expression in neurons may cause unwanted side effects, and are characterized by poor photophysics (absorbance, photocurrents, ion selectivity).
In this project aim to combine endogenous light-delivery through targeted expression of luciferases [1] and photopharmacology [2], which leverages light control over endogenous neurotransmitter receptors. To demonstrate the feasibility of this approach, the student will express luciferases in one cell and target endogenous neurotransmitter receptors in another. He/she will create co-cultures and incubate them with molecular photoswitchable compounds that are color-matched to the emitted light, and which, once activated, bind to and trigger the specific receptor. Importantly, this approach leverages the expertise of both teams in optogenetics and photopharmacology and will overcome challenges in light delivery to activate endogenous receptors to open the door to new treatment options in applied medicine. 
This project will be carried out at ICFO in the NMSB lab in collaboration with IBEC under co-supervision of Pau Gorostiza and Galyna Malieieva from the Nanoprobes and Nanoswitches group.

[1] Porta-de-la-Riva, Nature Methods, 2023; Neurophotonics, 2024
[2] Castagna, FEBS3+, 2022

photopharmacology, bioluminescence, optogenetics, photoswitches, neuroscience, neural engineering

https://iciq.org/research-group/prof-nuria-lopez/overview/

We will use atomistic simulations and Artificial Intelligence techniques to develop materials for chemical transformations that recycle CO2 into chemicals and fuels.

Light-driven systems for energy, health and environmental remediation.

https://iciq.org/research-group/prof-katherine-villa/overview/

Photodynamic therapy (PDT) is a minimally invasive treatment strategy that uses light-activated photosensitizers to generate cytotoxic reactive oxygen species (ROS) for the selective destruction of cancer cells and pathogenic microorganisms. However, its efficacy is often limited by insufficient photosensitizer accumulation at the target site and poor light penetration in complex biological environments. Light-driven micromotors offer a promising solution by providing autonomous motion, enhanced diffusion, and active targeting capabilities at the microscale.
This project aims to develop and characterize near-infrared (NIR)-driven photocatalytic nanomotors capable of delivering photosensitizers and boosting local ROS generation under light irradiation. The student will synthesize micromotors based on inorganic semiconductors, functionalized with molecular photosensitizers. Upon illumination, these micromotors will simultaneously self-propel through fluid media and activate photodynamic pathways, enabling light-triggered therapeutic action.
This interdisciplinary project integrates materials science, physical chemistry, soft robotics, and nanotechnology. The student will gain experience in micromotor fabrication, surface functionalization, optical microscopy, motion tracking, spectroscopy, and basic biological assays.

https://icn2.cat/en/advanced-electronic-materials-and-devices-group

Ultrasound (US) imaging is a key technology in medical practice that has undergone outstanding improvements in spatial and temporal resolution over the last 20 years. Commercial ultrasound transducers allow non-invasive, real-time 3D imaging of deep tissues enabling diagnostic and therapeutic applications in areas such as cardiovascular disease. However, current ultrasonic transducers are bulky and expensive, which limits its applicability and accessibility. The development of cheap and wearable US transducers could hence allow continuous monitoring of critical medical parameters that are currently inaccessible in a continuous manner. To this end, we will explore microfabrication of ultrasonic transducers in thin, flexible substrates to overcome state-of-the-art limitations in sensitivity and contrast. The execution of this Project will involve some of the following activities: ultrasonic device simulation and design, clean-room microfabrication (e-beam evaporation, UV-photolitography, wet etching and reactive ion etching), and ultrasonic transducer electrical characterization.

Keywords: Flexible electronics, Imaging, Microfabrication, Medical ultrasound, Wearable.

Quantum Materials at Atomic-Scale and AI development to automate STEM data analysis routines

https://gaen.cat/

Nanotechnology has had a profound impact on various fields, including materials science, electronics, medicine, and energy production. To gain a comprehensive understanding of nanomaterials and optimize their properties, it is essential to characterize their structure and composition at the atomic scale. Transmission Electron Microscopy (TEM) has emerged as a technique that allows for atomic scale imaging, coupled with spectroscopic methods such as electron energy loss spectroscopy (EELS), providing spatially resolved information about composition, valence state, and plasmonics and phononics. These techniques permit the correlation of physicochemical properties with atomic structure and composition, leading to a full understanding of nanoscale systems. In this context, the student will focus on the atomic scale characterization of quantum materials and devices, aiming to unravel the role of atomic arrangement in their properties, such as defect formation and elemental segregation. The project will be in collaboration with research groups from the École Polytechnique Fédérale de Lausanne or the Niels Bohr Institute of the University of Copenhagen, and experimental measurements will be conducted at the Joint Electron Microscopy Center at ALBA Synchrotron (JEMCA) using brand new TEM facilities to analyze materials at sub-nanometer scales. The student will also create 3D atomic models to simulate and interpret the acquired data and develop AI automated routines for high throughput data analysis. As a summary, the student will: Participate as an active member of the Group of Advanced Electron Nanoscopy of ICN2 attending to group meetings and interacting with the rest of the team Acquire knowledge in aberration-corrected TEM and its associated spectroscopies and AI programming Acquire knowledge in data interpretation and analysis combined with the creation of 3D atomic models and simulations Correlate the experimentally obtained atomic arrangement with the growth mechanisms and physicochemical properties of the nanostructures

https://ams.icn2.cat/

Scanning tunneling luminescence (STML) and tip-enhanced photoluminescence (TEPL) are powerful techniques capable of resolving light-matter interactions at the single-molecule and atomic scales. However, studying light-emitting nano-objects like single molecules or atoms typically requires their placement on metal substrates, where strong interactions quench light emission and distort electronic structure. This master project investigates how semiconducting two-dimensional (2D) materials can serve as electronic decoupling layers to preserve the optical and electronic properties of nano-objects during STML and TEPL experiments. Two-dimensional buffer layers will be prepared using in-situ growth techniques, including molecular beam epitaxy and chemical vapor deposition. Upon successful integration, nano-objects will be characterized by combining TEPL and STML with femtosecond pulsed laser excitation, enabling real-time observation of exciton dynamics, energy transfer processes, and charge carrier relaxation at unprecedented spatio-temporal resolution. The findings will establish design principles for effective decoupling architectures applicable to organic electronics, single-photon emitters, and nanoscale sensing or light-harvesting devices.

The project will be conducted at the PicoAtom Lab, a cutting-edge facility within the newly established Advanced Scanning Probe Microscopy Platform at ALBA Synchrotron. The student will gain hands-on expertise in advanced optical systems, ultra-high vacuum technology, and nano-materials fabrication while developing critical competencies in data analysis, scientific reasoning and academic writing.

https://nanodevices.icn2.cat/

Our understanding of condensed matter physics is undergoing a dramatic paradigm shift with the advent of two-dimensional materials (2DMs), which enable the engineering of material properties on demand. By precisely stacking layers of selected 2D crystals, researchers can now design artificial materials—so-called van der Waals (vdW) heterostructures—that combine and enhance the functionalities of their individual components.

Due to their atomically thin nature, 2DMs can acquire properties from neighboring materials that they do not possess in isolation. This proximity effect opens the door to band structure engineering, providing a powerful tool to induce novel electronic, magnetic, and topological properties. For example, it is possible to induce magnetism in non-magnetic materials like graphene or to realize non-trivial topological phases by integrating materials with strong spin-orbit coupling. These capabilities hold significant promise for applications in quantum metrology, quantum information processing, and memory technologies.

Our group conducts experimental research in this field by designing novel quantum materials through proximity effects and probing their properties via quantum and spin transport experiments, complemented by advanced characterization techniques. Students joining the team will collaborate with senior researchers and PhD students on these cutting-edge topics, gaining the opportunity to envision and create new materials that host previously unexplored physical phenomena. These materials will then be studied in custom-fabricated mesoscopic devices. The master’s work will place particular emphasis on scientific training in band structure engineering, spin transport and spin-orbit physics, device nanofabrication, and advanced characterization techniques.

https://www.nanobiosensors.org/

Daniel Quesada González

Rapid detection of pathogenic agents is essential for safeguarding public health, ensuring pandemics prevention and biodefense readiness, enabling early intervention during outbreaks. However, conventional laboratory analytical methods require sample transport and processing, expensive equipment, trained personnel and ends up providing a delayed response.
In this project, it will be developed a nanoparticle-based lateral flow biosensor for on-site testing, where the patient or the outbreak could be located, providing a readable response just within minutes.
The objectives will include: synthesis and characterization of nanomaterials; conjugation of nanomaterials with bioreceptors; lateral flow strips design and development; testing the biosensors in a controlled laboratory environment.

Data-Driven Optimisation of High-Entropy and Multimetallic Nanoparticles for Energy Conversion and Storage

https://icn2.cat/en/inorganic-nanoparticles-group

This Master’s project focuses on the wet-chemistry synthesis of multimetallic and high-entropy alloy (HEA) nanoparticles. The student will design, perform, and data-drive optimise colloidal wet-chemistry routes to obtain nanoparticles with controlled composition, size, and morphology, using scalable and environmentally benign approaches where possible. Key synthesis parameters—such as metal precursor ratios, reaction temperature, reducing agents, solvents, and stabilising ligands—will be systematically varied to investigate their influence on nanoparticle nucleation, growth, and structural complexity.
Structural and compositional characterisation will be carried out using techniques such as UV–Vis spectroscopy, X-ray diffraction (XRD), and electron microscopy, with training and support from specialised characterisation facilities. The resulting datasets will be used to identify trends aiming to establish synthesis–structure relationships through systematic experimentation and analysis.
An important aspect of the project is the rigorous documentation of experimental procedures and results. The student will record synthesis protocols, reaction conditions, and characterisation data in a structured, machine-readable format, following FAIR data principles. These curated datasets will form the basis for data-driven optimisation strategies and contribute to larger experimental databases used in data-driven optimisation and AI-assisted materials research.
This project provides hands-on training in colloidal nanoparticle synthesis and fundamental characterisation techniques, offering a solid experimental foundation in wet-chemical nanomaterials synthesis. It is well suited for Master’s students seeking practical research experience and preparation for advanced studies or a future PhD in nanoscience or materials chemistry.

High-entropy alloys, Wet-chemistry synthesis, Materials characterization, AI-assisted materials research

Mitochondrial disease evaluation through point-of-care serological testing (MITEST)

https://www.nanobiosensors.org/

Ana Victoria Lechuga-Vieco

Primary mitochondrial diseases are multisystem disorders that significantly impact lifespan and quality of life and often manifest during childhood. Most are caused by maternally inherited mitochondrial DNA (mtDNA) mutations, which frequently coexist with healthy mtDNA within the same cell, a condition known as heteroplasmy. The proportion of defective mtDNA and the resulting impairment in energy production largely determine disease severity, leading to highly variable clinical presentations. Traditional diagnostic approaches, such as muscle biopsies, are invasive, provide only a limited and localised view of the disease, and are not suitable for continuous monitoring. In addition, mtDNA mutation analysis in blood cells often underestimates the mutant load present in highly energy-demanding tissues, such as the heart, which frequently harbour higher levels of pathogenic variants. To address these limitations, this project proposes the development of a point-of-care (PoC) diagnostic approach based on circulating cell-free mitochondrial DNA (ccf-mtDNA) as a non-invasive biomarker for mitochondrial disease. ccf-mtDNA reflects mitochondrial dysfunction and cellular stress and offers a dynamic readout of disease progression and response to treatment. Rapidly and robustly measuring mutated mtDNA levels in small volumes of body fluids could therefore enable earlier diagnosis, improved patient stratification, and longitudinal disease monitoring.
In this project, the master’s student will contribute to the development and validation of a PoC diagnostic test that will isolate and quantify ccf-mtDNA from plasma samples then assess mtDNA copy number and heteroplasmy, in a low cost and easy to use d diagnostic device. The work will involve sample processing, microfluidic device development, quantitative PCR-based assays, electrochemical sensor development and basic data analysis to evaluate the robustness and sensitivity of the approach. Through this project, the student will gain hands-on experience in PoC diagnostic test development, electrochemistry, microfluidics and interdisciplinary methodologies relevant to precision medicine. The student will also have the opportunity to attend training courses and seminars at the host institute to broaden their technical and conceptual skills.

https://ams.icn2.cat/

Scanning tunneling luminescence (STML) and tip-enhanced photoluminescence (TEPL) are powerful techniques capable of resolving light-matter interactions at the single-molecule and atomic scales. However, studying light-emitting nano-objects like single molecules or atoms typically requires their placement on metal substrates, where strong interactions quench light emission and distort electronic structure. This master project investigates how two-dimensional (2D) materials (e.g., graphene, hexagonal boron nitride, and phosphorene) can serve as electronic decoupling layers to preserve the optical and electronic properties of nano-objects during STML and TEPL experiments. Two-dimensional buffer layers will be prepared using in-situ growth techniques, including molecular beam epitaxy and chemical vapor deposition. Upon successful integration, nano-objects will be characterized by combining TEPL and STML with femtosecond pulsed laser excitation, enabling real-time observation of exciton dynamics, energy transfer processes, and charge carrier relaxation at unprecedented spatio-temporal resolution. The findings will establish design principles for effective decoupling architectures applicable to organic electronics, single-photon emitters, and nanoscale sensing or light-harvesting devices.

The project will be conducted at the PicoAtom Lab, a cutting-edge facility within the newly established Advanced Scanning Probe Microscopy Platform at ALBA Synchrotron. The student will gain hands-on expertise in advanced optical systems, ultra-high vacuum technology, and nano-materials fabrication while developing critical competencies in data analysis, scientific reasoning and academic writing.

excitons in 2D materials, van der Waals heterostructures, scanning tunneling microscopy, optical nanospectroscopy,

https://ams.icn2.cat/

Bottom-up grown nanoporous graphene (NPG) is a novel nanomaterial, grown by the lateral fusion of armchair graphene nanoribbons (aGNRs). It has graphene-like structure, containing a highly ordered network of atomically precise nanopores. However, unlike graphene, NPG is semiconducting and has a technologically-relevant bandgap of around 2eV, opening up a possibility of applying it as a channel material in logic devices. NPG is highly promising for applications in (nano)electronics, optoelectronics, or sensing.
This project concerns full automatization and optimization of the growth process of nanoporous graphene in the semi-industrial scale of 2.5cm. It will involve upgrading existing large-area synthesis chamber with the automated leak valve for argon sputtering, its calibration, programming and integration with the process control software. A systematic study of the influence of growth parameters on the properties of the material will then be conducted. Three main parameters will be optimized: coverage of the surface with precursor molecules, annealing temperatures and annealing times. This will be followed by the determination of process reproducibility and sample homogeneity. The project will yield optimized and automatized protocol for growing homogeneous, high-quality nanoporous graphene, and will serve as a starting point for progressing towards real-world applications of the material.

nanoporous graphene, atomically precise nanoengineering, on-surface synthesis, automatization of instrument control

https://www.ifae.es/groups/medical#description

Positron Emission Tomography (PET) is a cornerstone of modern nuclear medicine, widely used for cancer diagnosis, staging, and therapy monitoring. Despite its clinical importance, PET performance is ultimately limited by the physics of gamma-ray detection. The CHLOE-PET project, funded by an ERC Starting Grant, aims to overcome these limitations by developing a novel gamma radiation detector and enabling a new concept of PET scanner with enhanced image quality and improved diagnostic potential.

This project is positioned at the intersection of applied and fundamental physics, offering students the opportunity to engage with cutting-edge detector science while contributing to a clinically relevant challenge. The work focuses on gamma detector physics, including detector characterization, timing and energy performance studies.

In addition to experimental work, the project involves advanced data analysis and computational techniques. The student will analyze detector data, implement and test self-calibration algorithms, and study their impact on image formation and quantitative image metrics. Depending on interests and background, the project may also include simulations, signal processing, or image reconstruction tasks.

The CHLOE-PET project offers flexibility, allowing the scientific focus to be tailored toward instrumentation development, computational analysis, or more fundamental physics questions related to gamma detection and timing. The student will work within an active research environment, closely connected to lab members that work on other research projects with overlapping technologies and methodologies.

This project is particularly suited to students motivated by hands-on experimentation and the opportunity to connect radiation-matter interaction principles with biomedical imaging applications.

https://www.irbbarcelona.org/en/research/pediatric-cancer-epigenetics

Ewing Sarcoma (EWS) is an aggressive bone and soft tissue cancer that affects predominantly children and young adults, with a peak incidence at 15 years of age. Prognosis of EWS patients is poor, with fewer than 30 % of patients surviving 5 years if their disease is metastatic at diagnosis. Identifying novel and personalised treatment strategies for EWS is therefore an undisputable and urgent clinical need. Even though different fusion oncogenes can drive EWS, EWSR1-FLI1 is by far the most prevalent translocation in patients (85-90% of cases). Molecularly, EWSR1-FLI1 triggers profound global transcriptomic and epigenomic reprogramming, yet the functional repercussions of EWSR1-FLI1 expression hugely depend on the affected cell. Oncogenesis only occurs if the affected cell has oncogenic competence, a term that refers to a molecular framework and cellular context permissive for oncogenic transformation.
Our preliminary data indicate that oncogene expression in human mesenchymal stem cells (hMSCs), previously suggested to be the EWS cell-of-origin, failed to recapitulate the defined EWS transcriptional signature. Indeed, the generation of EWS model systems based on oncogene expression in MSCs has been extensively attempted, to no avail. We therefore hypothesize that not MSCs, but instead a yet undefined developmental progenitor cells is the cell-of-origin of EWS.
Here we propose to adapt the 3D in vitro gastruloid model of mammalian development to the study of Ewing sarcoma initiation by employing genomically engineered mESCs that allow tight control of EWSR1-FLI1 induction in time and space. Using this model we aim to experimentally identify and functionally assign molecular pathways to EWSR1-FLI1 epigenetically-driven oncogenic transformation. We will integrate transcriptomic and epigenomic profiles of gastruloid-derived cells to (i) understand how epigenomic dysregulation leads to malignant transformation in EWS; (ii) identify which cell states during development are able to support EWSR1-FLI1 expression, and may thus constitute EWS cell(s)-of-origin. Ultimately, based on our emerging understanding of EWS biology, we hope to unearth novel, effective and specific intervention nodes for the treatment of EWS cancer patients.

https://www.irbbarcelona.org/en/research/signalling-and-cell-cycle-laboratory

A major focus of the group’s research is to understand how the p38 MAPK pathway integrates signals and how this regulation influences both physiological and pathological processes. Increasing evidence indicates that p38a plays important roles in maintaining normal tissue homeostasis, but can also be co-opted during tumorigenesis to promote cancer development and resistance to therapy.
Our work combines biochemical and molecular biology methods with studies in cultured cells, mouse models, and chemical-based approaches.
The group aims to uncover new therapeutic opportunities based on the modulation p38 MAPK-dependent mechanisms that govern cancer cell fitness and responses to chemotherapy. We are also conducting screens to identify actionable targets that could enhance current cancer treatments or guide the development of new targeted therapies for specific cancer types.
The student will work under the daily supervision of an experienced group member, who will provide training in laboratory techniques, experimental design, data analysis and interpretation, and proper scientific record-keeping in the lab notebook.

signaling network, tumorigenesis, cancer cell fitness, chemotherapy resistance, therapeutic opportunities

https://www.irbbarcelona.org/es/research/lluis-ribas

A disruption in the efficiency and fidelity of protein synthesis is a hallmark of cancer and aging, and it has important therapeutic implications. In cancer, modifications in the translation machinery favor the expression of proliferative genetic programs. On the other hand, compositional variations of the tumor’s proteome directly impact upon the immune recognition of the cancer cells. In aging, the loss of protein synthesis capacity causes sarcopenia and frailty, and the precipitation of improperly folded proteins is a key feature of neurodegeneration.

Despite these clear links between impaired protein synthesis and disease or aging, the molecular reasons why sick or aging cells lose their ability to make proteins are unknown.

We have discovered a new mechanism that directly affects the efficiency and the fidelity of gene translation in an age-dependent manner, and want to explore its impact upon tumor formation and tissue senescence.We need enthusiastic hands to help us explore this further, so we are looking for M.Sc. students interested in studying this molecular events. Students interested in both experimental or bioinformatics approaches will be considered.

References:
Murillo et al., (2025) Genome Research, In press.
doi: https://doi.org/10.1101/2025.06.09.658696.

https://cgenomics.org/

The human oral microbiome is a highly complex and dynamic ecosystem whose dysbiosis is critically linked to systemic health and disease. We invite an enthusiastic Master's student to join our multidisciplinary team to investigate these fundamental relationships, offering a flexible, hands-on research project that can be tailored to align with either experimental or computational expertise. For students favoring wet-lab work, the project involves mastering advanced microbiological techniques, including the selective isolation and characterization of key bacterial and fungal species from clinical samples, investigating the modulatory impact of novel molecular compounds using robust in-vitro and ex-vivo assays, and systematically unraveling complex fungal-bacterial-host interactions using co-culture models and microscopy. Alternatively, for students with a strong computational background, the project offers intensive training in bioinformatics, focusing on the processing and interpretation of high-throughput sequencing data, specifically analyzing amplicon-based (16S/ITS) and shotgun metagenomics datasets to assess community structure, predict functional pathways, and integrate sequencing results with our experimental findings to generate robust biological insights. This project is ideal for an ambitious candidate seeking to develop a comprehensive set of skills in cutting-edge experimental and analytical science, providing an excellent foundation for a future PhD in infectious disease or biomedicine.

microbiome, metagenomics, oral microbiome, complex microbial ecosystems, microbiology

https://www.irbbarcelona.org/ca/research/cell-signaling

Cells are constantly challenged by environmental fluctuations and must rapidly rewire their internal circuitry to meet new demands while maintaining their identity and maximizing fitness. Failure to adapt can lead to decreased cellular function, impaired survival, and ultimately cell death.
Our lab seeks to unravel the molecular mechanisms behind these adaptive processes, focusing on signaling pathways and adaptive responses that shape cell fate decisions. Our multidisciplinary approach combines cutting-edge techniques in proteomics, genomics, transcriptomics, and single-cell analyses to decode the language of cellular adaptation.

Master's students will have the opportunity to engage in innovative research projects:
-Discover novel gene functions essential for stress adaptation through genetic screens (CRISPR screens in yeast or mammalian systems)
-Biochemically identify novel targets controlled by stress-activated protein kinases and define their impact on cell physiology
-Leverage cutting-edge single-cell RNA sequencing (scRNA-seq) to uncover heterogeneity in adaptive responses
-Link molecular profiles to phenotypic outcomes to gain insights into diverse cellular strategies for adaptation

Together, we aim to define novel mechanisms controlling cellular adaptation and bridge the gap between molecular signatures and cellular behavior.
Join our stimulating and collaborative scientific environment, where you will work alongside a multidisciplinary team and engage with international collaborators. By understanding how cells mount adaptive responses, we aim to unlock new insights into health and disease.

Stress adaptation, Signaling, SAPK, single cell analysis, cell cycle regulation, transcriptional regulation

https://www.irbbarcelona.org/en/research/marco-milan

Chromosomal Instability in development and disease: beyond cancer evolution
Chromosomal instability (CIN), an increased rate of changes in chromosome structure and number, has been classically associated with human disease as a way of evolving the cancer genome. In recent years, three additional research lines concerning the impact of CIN on human disease have been consolidated. First, beyond the generation of genomic copy number heterogeneity, CIN acts as a source of tumor growth, metastasis, and malignancy through additional mechanisms. Second, CIN is pervasive in early human development, and the resulting aneuploid cells are selectively removed from the fetus to give rise to healthy births. Third, CIN is associated with mosaic variegated aneuploidy, a rare familial disease that compromises brain development and contributes to tumor formation. Our lab uses Drosophila as model system to address these three topics with a particular emphasis on the role of aneuploidy in normal development, cell competition and disease.

https://www.irbbarcelona.org/es/research/mitochondrial-biology-and-tissue-regeneration

The immune system plays a crucial role in maintaining physiological homeostasis. The ageing immune system is characterised by chronic inflammation, reduced immune function and diminished tissue repair capacity. These alterations can disrupt the equilibrium of homeostasis in energetic tissues, leading to impaired function and increased susceptibility to disease. Understanding the interactions between T cells, tissue homeostasis, and ageing holds the potential to provide new therapeutic approaches for age-related diseases. Recent studies have highlighted the importance of mitochondria in immune cell function and ageing. As mitochondrial quality control declines with age, immune cell metabolism and function are also compromised, contributing to immune senescence and giving rise to various aging-related features such as metabolic and cardiovascular pathology.

This project aims to elucidate the role of mitochondrial quality control mechanisms in shaping the transcriptional programmes of immune cells and their contribution to the transition to immune senescence, cytokine production, and inflammatory responses during the aging of highly energetic tissues. It combines a diverse range of molecular biology methods and immunophenotyping, including confocal microscopy, ELISA analyses, primary cell cultures, and spectral flow cytometry. Specific T cell subsets will be correlated with tissue damage in aged mice through comprehensive metabolic immune profiling, utilizing preclinical models of premature aging. Relevant mitochondrial quality control pathways will be validated using pharmacological treatments in mouse experimental models. Additional techniques may include high-throughput sequencing, western blotting, immunoprecipitation, and mitochondrial biology approaches to study mitochondrial structure, function, and regulation, as well as overall organelle function.

The student will carry out this work within a highly dynamic and collaborative laboratory environment, with regular exposure to interdisciplinary discussions, internal seminars, and shared expertise across complementary research groups. Additionally, the student will take part in specialised courses, workshops, and training activities available at the host institute, supporting both technical development and broader scientific skills.

mitochondrial quality control, immunometabolism, senescence, age-related diseases

Revealing the adaptations of dendritic cells to changing environments in health and non-infectious diseases

https://www.irbbarcelona.org/en/research/innate-immune-biology

Innate immune cells, such as dendritic cells, control immunity and the health of organs. Therefore, they are present in virtually all body tissues. We aim to understand how innate immune cells can persist in and adapt to different milieus of tissues, such as limited nutrient concentrations and other variables. In that regard, our main research line focuses on revealing the adjustments of the cellular metabolism by dendritic cells to changing environments in health, aging, cancer and obesity-related pathologies. Our ultimate goal is to identify the requirements or vulnerabilities of dendritic cells to improve or target their dysfunctions during those non-infectious diseases by “innate immunotherapies”. The detailed Master’s project is flexible and will be designed together with the successful candidate based on her/his interests within our research lines.
We are looking for a motivated Master candidate to investigate the homeostatic and immunogenic behaviour of dendritic cells under different environmental or metabolic conditions in vivo and in vitro. This will include the variation of metabolites, temperature, pH, genetic interference with cellular metabolism and/or other alterations of the surroundings. Our main model systems are laboratory mice and we will provide training in harvesting and processing their organs for research. Moreover, the candidate will perform analyses of the functions of innate immune cells, such as migration, phagocytosis, expression of functional markers and cytokine production. Subsequent experimental techniques will include the isolation or differentiation of innate immune cells for primary cell culture, co-culture assays, flow cytometry, gene expression analysis, ELISA, fluorescence microscopy and metabolic assays. Additionally, we offer teaching of experimental design, data analysis, visualisation and interpretation as well as help with the oral presentation of the candidate’s research results.

Decipher microtubule network organization in pluripotent stem cells and derived neuroepithelium

https://www.irbbarcelona.org/en/research/microtubule-organization-cell-proliferation-and-differentiation

This project aims to elucidate the microtubule network in induced pluripotent stem cells (iPSCs), and how it is remodeled during differentiation of iPSCs into neuroepithelium-like neural rosettes.

The microtubule cytoskeleton provides cells with mechanical support, mediates intracellular transport, positions organelles, and segregates the chromosomes during cell division. These functions are crucial for the formation and maintenance of different types of tissues including the neuroepithelium. Indeed, malfunctioning of the microtubule cytoskeleton has been linked to both impaired neurodevelopment and neurodegeneration. However, how cell type-specific microtubule arrays are organized to carry out different functions is still poorly understood.

The project aims to reveal the overall microtubule network configurations, identify microtubule organizing centers (MTOCs), and describe changes that occur during neural differentiation.

The student will learn the culture and neural differentiation of iPSCs, advanced microscopic imaging techniques, and a range of assays to determine microtubule nucleation, growth and polarity, and composition and function of microtubule organizing centers (MTOCs) such as the centrosome. This will uncover fundamental principles of microtubule network organization in stem cells and derived neural rosettes that are highly relevant for development and disease.

https://www.upf.edu/web/cancer-biology

Genomic instability, a hallmark of cancer, is a direct consequence of the inactivation of the tumour suppressor protein p53. Genetically modified mouse models and human tumour samples have revealed that p53 loss results in extensive chromosomal abnormalities, from copy number alterations to structural rearrangements, and correlate with poor prognosis and therapy resistance. Immunotherapy has revolutionised cancer treatment. It is based on
neutralising T cell repressive receptors that inhibit their capacity to attack the tumour and it is particularly effective against tumours with high mutational burden. However, despite the high immunogenicity expected in patients with genomically unstable cancers due to defects in DNA damage repair genes, clinical response rates are often limited. This discrepancy is partly due to the activity of the nonsense-mediated mRNA decay (NMD) pathway, which
degrades mutated transcripts and suppresses the presentation of potentially immunogenic neoantigens. Our proposal, addresses this critical barrier by developing novel pharmacological inhibitors of NMD (NMDi) to unlock hidden neoantigens, thereby converting immunologically cold tumors into hot ones. This interdisciplinary approach, combining medicinal chemistry and cancer immunology lays the foundation for a new generation of personalised treatments in cancer care.

PROTECTING HEMATOPOIETIC STEM CELLS (HSC) FROM INFLAMMATORY STRESS

https://www.upf.edu/web/genimmune

We will address a major challenge related to stem cell fitness and aging, supported by the
interdisciplinary expertise of our group, cutting-edge methodologies, experimental models of disease in mice, access to state-of-the-art core facilities, expert collaborators, and funding from national and international grants.
Hematopoietic reconstitution after stress, trauma or infection requires hematopoietic stem cells (HSCs) mobilization from quiescence, a process that makes them highly vulnerable to
inflammatory signals that can exhaust the HSC pool. We have identified a mechanism that limits systemic production of type I interferons (IFN-I) by inflammatory cells in vivo, thus protecting HSCs from excess exogenous IFN-I while allowing for IFN-I protection against infection.
In this project, we will study what inflammatory signals target directly stem cells under chronic inflammatory stress signals that increase during aging. We will also analyse how stem cells deploy protective mechanisms that safeguard their viability, long-term progenitor potential and reconstitution function in response to chronic inflammation. Elucidating these mechanisms has interest in clinical haematology, and could advance knowledge on stem cell function in other systems.

https://www.upf.edu/web/osccg

Cancer is a leading cause of mortality worldwide and is characterized by uncontrolled and aberrant cell proliferation. Under physiological conditions, the cell cycle is tightly regulated by a complex network of pathways, including cell-cycle checkpoints, DNA replication, DNA repair, and cell division. In higher eukaryotes, the Restriction Point is a key checkpoint located at the end of G1 phase, after which cells become committed to completing a full cell-cycle round and no longer depend on extracellular signals to drive division. Fission yeast is an excellent model for studying cell-cycle regulation due to the high conservation of its core regulatory networks with metazoans, combined with the experimental advantages of a unicellular haploid organism.

The aim of this project is to screen two genetic libraries—kinase mutants and mutants affecting ubiquitin-mediated protein degradation—to identify regulators of the basal activity of the MBF transcriptional complex and to determine the consequences of impaired MBF post-translational modifications on DNA damage responses and genome integrity. This project is based in two recent publications of our group: Murciano-Julia, PLoS Biol, 2025a (PMID: 39775128); Murciano-Julia, EMBO Rep. Biol, 2025b (PMID: 40883509).

Required student background: A high motivation towards a scientific career, a solid background in Genetics, Cell Biology and Molecular Biology is a plus to carry out this project. To analyze the results, some knowledge of bioinformatics will be beneficial for the candidate.

SantosMorenoLab.org

In the Synthetic Cell Programming lab (santosmorenolab.org) we focus on designing and building synthetic gene circuits that allow us to program the behaviour of microbes, a requirement for using them to tackle health and environmental challenges. In that regard, programming cells to operate autonomously over time can enable applications in which external control (e.g. through inducers) is not possible or desirable.

In the past we built synthetic molecular oscillators based on CRISPR interference (CRISPRi) in bacteria (Santos-Moreno et al. 2020, Nat Commun 11:2746), and we used them to control the biosynthesis of the bacterial capsule in an oscillatory manner (Rueff et al. 2023, Nat Commun 14:7454). We are currently working of alternative tools and circuit designs that allow us to program temporal actions to occur in a discrete – rather than oscillatory – manner.

You will contribute to the assessment and characterization of molecular tools (e.g. CRISPRi, transcription factors, recombinases…) that enable the construction of synthetic gene circuits to program temporal tasks in E. coli cells. Besides, you will participate in exploring potential applications of temporal circuits, such as biocontainment, bioproduction or molecular recording. The range of techniques and equipment you will have access to includes in silico gene circuit design, advanced cloning, microplate reader measurements, automated pipetting robot, flow cytometry, fluorescence microscopy, or microfluidics, among others.

santosmorenolab.org

In the Synthetic Cell Programming lab (santosmorenolab.org) we aim to engineer human skin bacteria for diagnostic and therapeutic applications. Indeed, skin conditions affect ~25% of the world population, and engineered microbes constitute an innovative approach to tackle human diseases. Cutibacterium acnes is the most abundant skin bacterium and stably colonizes the follicles, where its presence generally correlates with healthy skin. C. acnes is therefore an ideal chassis for medical applications, but its engineering has been hampered by unsuccessful DNA delivery into the bacterial cytoplasm and a resulting lack of molecular tools to program its behaviour.

In the past, we managed to significantly improve the delivery of DNA into C. acnes cells (Knödlseder et al. 2024, Nat Biotechnol 42:1661-1666), and this allowed us to establish the first molecular toolbox to engineer this bacterium – including promoters, reporters, CRISPRi, recombinases, transcription factors… (Nevot et al. 2025, Cell Systems 16: 101169). Besides, we provided a proof-of-concept demonstration of the potential of this bacterium for medical purposes by developing strains that secrete anti-acne and anti-oxidant proteins (Knödlseder et al.) (Nevot et al.). We are currently working of new tools that allow us to engineer strains that are safer for prospective deployment on the human skin, and that interact with other members of the human microbiome in new ways, e.g. by limiting the growth of pathogenic bacteria or by cross-talking with other engineered human commensals.

You will contribute to the assessment and characterization of molecular tools (CRISPR editing, unstable plasmids, antimicrobials…) that enable the construction of safer C. acnes strains. Besides, you will participate in exploring potential interaction channels between C. acnes and other human bacteria. The range of techniques and equipment you will have access to includes in silico plasmid design, advanced cloning, anaerobic cultivation, automated pipetting robot, flow cytometry, or fluorescence microscopy, among others.

Synthetic biology, skin microbiome engineering, CRISPR editing, antimicrobials, intercellular communication

N-glycosylation modulation and selective inhibition of CaV2.1 in pathological CACNA1A mutations: toward targeted and personalized therapies

https://www.upf.edu/web/lmp/

José Manuel Fernández Fernández

Gain-of-function (GOF) mutations in CACNA1A (encoding the 1A subunit of the CaV2.1 calcium channel) cause multiple neurological disorders including familial hemiplegic migraine (FHM1), congenital ataxia (CA), and developmental and epileptic encephalopathy (DEE42). Despite advances in genetics, specific targeted therapies remain limited.

We have identified six novel, selective CaV2.1 inhibitors. Two of them show greater suppression effect on channels carrying HM-associated pathological mutations when compared with wild-type, and one normalized hyperactive neuronal network from a murine FHM1 animal model. Promoting glycosylation through phosphomannose isomerase inhibition plus mannose supplementation can also partially reverse GOF effects in some mutations but not in others, suggesting that therapeutic efficacy depends on mutation and affected channel domain.

We will integrate electrophysiology techniques, calcium imaging, and glycosylation analysis in three complementary cellular contexts: HEK293 cells as heterologous expression system, primary cortical neurons from FHM1 knockin mice (R192Q mutant), and patient iPSC-derived neurons.

In HEK293 cells, three pore domain mutations of unknown functional effect associated with epileptic phenotypes will be characterized: F363S, F1506S, and L1803R. Previous computational analyses indicate that F363S and F1506S destabilize the hydrophobic bundle that seals the inner gate of the channel, which would allow elevated calcium influx. Additionally, two voltage sensor mutations will be evaluated (R192Q and R583Q).

Patient iPSC-derived neurons will carry five different pathological CACNA1A mutations linked to FHM1, ataxia, and/or DEE42, affecting distinct functional domains of the channel: linker connector (S218L), pore (A713T and V1393M), and voltage sensors (R1349Q and R1667P).

Objectives: (1) functional characterization of F363S, F1506S, and L1803R in HEK293 cells; (2) determination of pharmacological profiles of the six CaV2.1 inhibitors against the ten pathogenic variants in heterologous and neuronal systems; (3) evaluation of N-glycosylation modulation on the GOF effects associated with each mutation; (4) creation of database linking channel structure, mutation, pharmacological efficacy, and response to hyperglycosylation.

CaV2.1 Inhibitors, Hyperglycosylation, Hemiplegic Migraine, Congenital Ataxia, Developmental and Epileptic Encephalopathy 42

www.gallegolab.org

Most of the living organisms in our planet are ectotherms, organisms that cannot control their “body” temperature. Yet ectotherms are vulnerable to fluctuations in the ambient temperature. Eukaryotic microorganisms are especially susceptible because their survival relies on more sophisticated membrane dynamics than prokaryotes. Thus, global warming is increasingly challenging the biodiversity of eukaryotic microorganisms and the ecological functions associated to these species. Unfortunately, the lack of knowledge about how species adapt their essential cellular processes to life-threating temperatures, hinders accurate predictions on the climate change impact and frustrates the efforts to develop remedies.

We offer a position for a master student to integrate advanced light and electron microscopy to investigate in situ the biophysical constraints that regulate the viability of cellular processes in front of temperature fluctuations. For this purpose, we will use various species of eukaryotic microorganisms, some of which will be isolated from alpine niches in the Pyrenees. We will exploit the diversity of organisms and quantitative live-cell imaging to deliver mechanistic knowledge.

Understanding the biophysical principles, and the molecular basis associated to them, that constrain eukaryotic microorganisms adaptation to specific thermal niches will allow us to narrow the gap towards understanding the principles that rule the origin and evolution of eukaryotes. The project involves the establishment of new model organisms in the laboratory as well as gene editing techniques. The student will learn super resolution microscopy, particle tracking and image analysis. We will also implement correlative cryo-light cryo-electron tomography methods to measure biophysical constraints in situ.

During the progression of the project the student will acquire a strong expertise in quantitative light microscopy and image analysis. Depending on the student’s skills and interest, the project could also involve modelling of 3D structures or machine learning for image analysis. The lab might provide economical support.

Live-cell imaging, Super resolution microscopy, cryo-Electron microscopy, Bioimage analysis, In situ Structural biology

https://www.upf.edu/web/lmp/

Zinc dyshomeostasis has been implicated in the aging process and age-related diseases, yet its precise role in longevity remains poorly understood. Considering the importance of ROS damage in aging, zinc plays complex, bidirectional roles in oxidative stress and redox homeostasis. Moreover, zinc excess impacts mitochondrial function, the respiratory chain, and ROS production. This is a molecular biology project that aims to dissect the importance of zinc signalling in aging focusing on mitochondria dynamics and ROS production with special attention to the nervous system and neurodegenerative disorders.

www.upf.edu/web/biocog

Preventing cognitive decline and neurodegeneration is a relevant problem in biomedical research. Aging is associated to the development of cognitive impairment, which can be reduced by treatments that target the endogenous cannabinoid system. Such treatments have been found to improve synaptic plasticity and cognitive performance. Studying animal models for Down syndrome, the main genetic cause of intellectual disability, we have found an approach to improve cognitive performance even in adult mice that show neuronal degeneration of specific cholinergic and noradrenergic populations. This approach, that has to do with the inhibition of the main cannabinoid receptor in the organism, may also interact with neuroinflammatory and senescence mechanisms. We will use in vivo (mouse models and behavioural analysis) and in vitro techniques (immunoblot, qPCR, immunofluorescence, confocal microscopy analysis, among others) to further explore cellular and molecular effects of cannabinoid receptor inhibition in the context of Down syndrome animal models to reveal the mechanisms of cognitive alleviation.

https://www.upf.edu/web/lmp/research

Background and Rationale
Alzheimer’s Disease (AD) is characterized by the extracellular accumulation of amyloid-β peptides (Aβ), which assemble into neurotoxic oligomers and fibrils. These aggregates are a primary driver of synaptotoxicity, leading to widespread neuronal loss. Currently, a critical clinical gap exists, as no treatments effectively cure, halt, or prevent disease progression.

Research Hypothesis
This study investigates the hypothesis that oligomeric Aβ (oAβ) impairs synaptic mechanoreceptor function—either through direct interaction or by inducing oxidative stress. We propose that this impairment disrupts the growth and structural stability of synaptic spines, which are regulated by mechanosensitive pathways, while concurrently inducing pathological elevations in intracellular calcium.

Key Objectives
The primary objective is to characterize how oAβ and associated oxidative stress modulate the activity of the mechanoreceptors TRPM7 and Piezo1 within synaptic spines. Given that these receptors govern the mechanical forces underlying dendritic growth and actin-dependent spine maintenance, we will assess how oAβ-mediated interference disrupts synaptic plasticity. A parallel aim is to investigate the role of these receptors in Aβ-induced dysregulation of calcium signaling.

https://felixcampelo.wixsite.com/home

Cells use intracellular trafficking and secretion to constantly exchange material with their surroundings. This is essential for maintaining cell and tissue organization, communication, and adaptation to different environments. At the same time, cells experience a wide range of extracellular physical cues, such as differences in matrix organization and mechanical constraints. How these environmental conditions influence intracellular trafficking and secretion remains an important open question in cell biology (see Bhaskar Naidu, Vera Lillo et al. bioRxiv, 2025).

This MSc project aims to explore how protein trafficking and secretion adapt to different cellular contexts and physical environments. The student will investigate how cells adjust the sorting, transport, and secretion of proteins when their shape, organization, or surroundings change. To do this, the project will use established cell biology approaches to monitor secretion in a controlled and quantitative manner. In particular, synchronized secretion assays (such as the RUSH system) will allow the timing and dynamics of protein transport through the secretory pathway to be followed by fluorescence microscopy.
The project will compare simple two-dimensional cell cultures with more structured or tissue-like models, including three-dimensional cell assemblies. In addition, cells will be grown on micropatterned substrates or under defined physical constraints to control cell shape, organization, and mechanical inputs from the environment. These model systems make it possible to examine how physical context influences intracellular organization, trafficking routes, and overall secretory output.

The student will analyze how changes in cellular context affect the behavior of trafficking pathways and secretion efficiency, and how secretion in turn contributes to shaping the local cellular environment. Overall, this project will inform us about how cells coordinate internal transport with external physical conditions. Understanding this interplay is key to explaining how cells maintain organization, respond to stress, and function within tissues, and it provides a solid foundation for future studies in cell mechanobiology and tissue organization.

Intracellular trafficking, protein secretion, Golgi apparatus, physical environment, extracellular matrix

https://felixcampelo.wixsite.com/home

Efficient protein secretion relies on accurate sorting at the trans-Golgi network (TGN), a key intracellular hub where cargoes are directed toward distinct destinations. Our recent work has identified TGN46 as an important sorting receptor whose luminal domain plays a central role in selective cargo export (Lujan et al. eLife, 2024). However, the molecular mechanisms by which this luminal domain regulates sorting, and how it may respond to cellular signals, are still unknown.

This MSc project will investigate the hypothesis that phosphorylation of the TGN46 luminal domain by the Golgi-resident kinase Fam20C modulates its sorting function. Phosphorylation within luminal or intrinsically disordered regions has emerged as a regulatory mechanism for protein-protein interactions and phase behavior, suggesting a potential link between biochemical modification and cargo selection at the TGN. In parallel, our recent studies indicate that secretory trafficking is sensitive to mechanical cues from the cellular environment (Bhaskar Naidu, Vera Lillo et al. bioRxiv, 2025), raising the possibility that mechanical inputs may indirectly influence TGN46-dependent sorting through signaling pathways that affect luminal phosphorylation.

The student will combine cell-based and biochemical approaches to test this hypothesis. In cells, synchronized secretion assays will be used to compare the trafficking behavior of wild-type and phosphorylation-deficient TGN46 variants under different conditions. These experiments will assess how luminal domain phosphorylation affects cargo sorting efficiency and export dynamics from the TGN. To complement this, the student will purify the luminal domain of TGN46 and analyze its biophysical properties in vitro. In particular, in vitro phase separation assays will be used to test whether the intrinsically disordered region of the luminal domain can form condensates together with cargo proteins, and whether phosphorylation alters this behavior.

Together, this project aims to connect molecular modification, biophysical properties, and cellular function of a Golgi sorting receptor. By linking luminal domain regulation to both intracellular trafficking and emerging concepts in mechanobiology, the project will provide mechanistic insight into how cells dynamically control protein secretion.

https://www.upf.edu/web/alsina_lab

During the formation of tissues and organs, cells change shape, move, interact with other cells and communicate to create a 3D organ in which cells are correctly positioned and differentiated. Sensory organs such as the lens, olfactory or inner ear derive from ectodermal placodes that in zebrafish, undergo a process of mesenchymal-epithelial transition (MET). The Alsina lab has long lasting experience investigating organ development through the combination of high spatiotemporal resolution imaging, genetic and mechanical perturbations (Hoijman et al., 2015 Nature Commun, Hoijman et al., 2017 eLife, Bañón and Alsina, 2023 Development). Recent quantitative data of cell and tissue shape changes, cell trajectories and epithelialization dynamics extracted after 3D organ segmentation, suggests that MET progresses anisotropically. Although we have a good description of the cell behaviours during the morphogenesis of the otic placode, it is still a mystery how mechanical forces impinge on cells to drive a particular 3D shape.
We hypothesize that MET progression and the final organ shape is influenced by mechanical forces from the surrounding tissues and the extracellular matrix. The aim of this project is to investigate, together with an experienced postdoctoral fellow, the mechanical role of the neural crest and laminin in shaping the otic placode. This project will be carried out at the lab of Dr. Alsina at Universitat Pompeu Fabra (UPF) and the Parc de Recerca Biomèdica de Barcelona (PRBB), one of the most dynamic research centers of the south of Europe. The student will learn the main principles of tissue and organ formation, will manipulate zebrafish embryos, develop new tools for force measurement in vivo and will learn state-of-the-art imaging technologies.

inner ear, biomechanics, epithelium, zebrafish, morphogenesis, imaging, 3D segmentation

https://felixcampelo.wixsite.com/home

The secretory pathway constitutes the main biosynthetic route for transmembrane proteins and soluble secreted factors, thereby governing the processing and export of more than 30% of the human proteome. Although the molecular determinants of protein secretion are well characterized, key questions remain unresolved. For instance, why does the trans-Golgi network (TGN) employ multiple export routes to deliver cargo from the Golgi to the plasma membrane? One possibility is that this diversity enables context-dependent regulation tailored to specific cellular needs.

Essential cellular processes—from inflammation to tissue regeneration—rely heavily on the secretory pathway. Yet, most mechanistic insights have been derived from 2D cell culture systems, despite the fact that cells in living tissues reside within 3D microenvironments, where they polarize and are subjected to mechanical forces. Recent work from our group has shown that the Golgi apparatus can sense and adapt to mechanical cues. By exposing adherent cells to substrates of varying stiffness, studying cell spreading on distinct extracellular coatings, or applying equibiaxial strain, we demonstrated that the Golgi mechanoresponses involve tubulin acetylation and an increase in Golgi membrane tension, correlating with enhanced formation of secretory carriers.

Building on this framework, we now investigate how extracellular matrix (ECM) stiffness and viscoelasticity influence secretion in physiologically relevant 3D contexts, using polarized cells cultured in complex ECM environments and patient-derived colorectal cancer organoids. We hypothesize that TGN export routes are differentially regulated in response to extracellular mechanical forces, thereby fine-tuning the cellular secretome. Understanding the crosstalk between Golgi mechanoadaptation and cellular behaviour may open new lines of research with important implications for human biology.

https://www.upf.edu/web/microbiome

Endometriosis is a chronic, progressive, and estrogen-dependent gynecological disease affecting up to 10% of reproductive-age women. It is characterized by the ectopic growth of endometrial-like tissue, driven by heightened estradiol signaling and progesterone resistance. These processes enable endometrial cells to survive, proliferate, and establish lesions outside the uterus, creating an inhospitable uterine environment for embryo implantation.

Although the pathophysiology of endometriosis remains incompletely understood, it is increasingly recognized as multifactorial, with emerging evidence implicating the gut and vaginal microbiomes. Microbiome dysbiosis may exacerbate inflammation, accelerate lesion progression, and impair fertility. However, inflammation alone cannot fully explain the disease, and the functional role of microbial metabolism in endometriosis remains largely unexplored. Microorganisms in the gut and vaginal microbiomes influence systemic and local sex hormone levels, thereby directly affecting reproductive physiology.

In this study, we investigate the gut and vaginal microbial metabolism of bioactive compounds, particularly sex hormones, as a key driver of endometriosis progression and manifestation. Moreover, we will also tackle the contribution of the gut microbiome in the gut-brain axis, producing neuroactive compounds that communicate with the hypothalamic-pituitary-gonadal (HPG) axis and other brain regions, ultimately regulating gonadal hormone production and pain sensitization. The overarching goal of this project is to elucidate microbiome-driven, metabolism-based mechanisms underlying endometriosis. Specifically, we will conduct a clinical study to identify the main microbial functional alterations in the vaginal and gut microbiome of endometriosis patients compared to healthy controls across the menstrual cycle (proliferative phase vs secretory phase). Blood, fecal, and vaginal samples will be collected (metagenomics, metabolomics, inflammatory biomarkers assay, hormonal characterization) together with extensive high-quality metadata.

Overall, this project integrates the establishment of a deeply phenotyped cohort diagnosed with high-accuracy standardized methods, with high-resolution sequencing techniques and cutting-edge bioinformatic tools, to ultimately contribute to advancing our knowledge of microbiome-based mechanisms in endometriosis, and lay the basis for more personalized and effective clinical management of this debilitating condition.

vaginal microbiome; gut microbiome; endometriosis; sex hormones; microbial metabolism

Use of Cell Routines and Molecular Pathways on Neuronal Diversity Generation in the Zebrafish Hindbrain

https://pujadeslab.upf.edu/

Embryonic development requires a thorough regulation of cell proliferation and cell differentiation to generate the right kind of cells, at the correct place and time and in the good proportions. This can be achieved by the spatiotemporal control of the mode of stem cell division, as well as the regulated activation of differentiation mechanisms. In the nervous system, neural stem cells divide symmetrically, generating two identical cells, either stem cells or neurons, or asymmetrically, originating another stem cell and a cell committed to neural differentiation or neuronal precursor. Furthermore, to achieve the astonishing cell diversity of the brain, different kinds of neurons must be produced from distinct progenitor cells.
In this project, we wish to focus on how metabolic and cellular stress can affect cell fate decisions in distinct cell lineages and compartments within the brain. Using pharmacological treatment or genetic modifications we plan to assess how the alteration of the proteostasis or genotoxic stress can affect differentiation, but also elucidate if these have a role in physiological conditions.
Finally, we wish to understand if and how the Notch pathway, one of the main binary cell fate decision pathways with a significant role in development, can regulate neuronal cell diversity. For that we will perform functional analysis of Notch activity and assess the impact on the differentiation of distinct brain lineages.
In all, imaging tools (3D+time imaging), gene expression assessment and alterations using genome-editing technology or pharmacological treatments will be combined using zebrafish embryos to assess the different aspects of neurogenesis stated above.

https://barniolxicotalab.com/

Cancer cells rewire their metabolism to survive, proliferate, and evade therapy. One emerging hallmark of this rewiring is altered lipid metabolism, which reshapes the plasma membrane and profoundly influences signaling, cell fate, and drug response. This MSc project focuses on a membrane-associated enzyme involved in lipid remodeling and immunometabolism, known to be overactive in aggressive and drug-resistant cancers. This enzyme plays a key role in regulating phospholipid composition and has been implicated in cancer progression, inflammatory signaling, and poor therapeutic outcomes, making it a highly attractive yet underexplored therapeutic target.
The central goal of the project is to develop and implement a robust screening platform to monitor the activity of this enzyme and enable the discovery of chemical modulators. You will work at the interface of chemical biology, biochemistry and assay development applied to drug discovery.
What you will do
• Design and optimize an activity-based HTP screening assay
• Work with enzymes, lipids and small molecules
• Generate quantitative data suitable for inhibitor discovery
• Gain hands-on experience with state-of-the-art chemical biology approaches
Why this project matters
By enabling the systematic discovery of inhibitors, this work has the potential to open new therapeutic avenues against drug-resistant breast cancer and to establish lipid-modifying enzymes as actionable targets in cancer immunometabolism.
Ideal candidate
Motivated MSc students with a background in chemistry, biochemistry, biotechnology or related fields, and an interest in cancer research, drug discovery and translational science.

Drug discovery, Cancer, Assay development, Immuno-metabolism, Drug resistance

https://ibecbarcelona.eu/targeted-therapeutics/

The project focuses on a congenital disorder due to mutations affecting a lysosomal enzyme called acid sphingomyelinase (ASM), which affects the central nervous system and peripheral organs. Recombinant ASM applied in the clinics does not help with neurological symptoms only since the blood-barrier barrier (BBB) prevents its access to the brain. The lab has identified new antibodies targeting ICAM-1, which induce transport across the BBB and into lysosomes. The project aims to design and characterize new recombinant fusion proteins containing ASM catalytic modules and antibody-derived ICAM-1 targeting modules for effective treatment. The student will contribute to the in vitro characterization of these recombinant proteins, which may encompass physicochemical characterization, validation of their different modular components, and testing of their functional activity. These tasks may involve recombinant, biochemical, molecular, and cellular biology techniques, such as electrophoresis, Western blotting, enzymatic reactions, ELISA, cell culture, flow cytometry, and/or optical microscopy. The student will develop competences in experimental design, data analysis, statistics, scientific reporting, and presentation. The internship will strengthen the student’s ability to work in an international research environment and collaborate within a multidisciplinary team, having continued supervision and guidance.

https://www.irbbarcelona.org/en/research/laboratory-of-molecular-biophysics

Autism spectrum disorder (ASD) is heterogeneous, and in most cases the molecular origin remains unclear. Recent work from our team revealed a mechanistic link between mis-splicing of a neuron-specific microexon in the RNA-binding protein CPEB4 and ASD-associated gene-expression defects. In neurons, CPEB4 forms activity-regulated condensates that normally dissolve upon depolarization, enabling a switch from translational repression to activation. Reduced inclusion of a 24-nucleotide microexon destabilizes these reversible assemblies and promotes pathological CPEB4 aggregation, leading to downstream dysregulation of neuronal gene-expression programs relevant to ASD (Garcia-Cabau, Bartomeu et al, Nature, 2025).

The aim of this project is to explore translational strategies emerging from this discovery, bridging fundamental biophysics and neuronal function toward therapeutic concepts and biomarkers. The student will work on (i) identifying actionable intervention points in the pathway connecting microexon inclusion, CPEB4 phase behavior, and translational control; and (ii) designing experimental or computational workflows to assess therapeutic feasibility.

Possible directions include: mapping candidate molecular modulators of CPEB4 condensation/aggregation (e.g., peptide mimetics, small-molecule screening concepts, or post-translational modification targets), prioritizing splicing-correction strategies (e.g., antisense oligonucleotide logic to restore microexon inclusion), and defining measurable cellular readouts that could support biomarker development (condensate dynamics, aggregation signatures, and target mRNA translation profiles).

This interdisciplinary project will provide training in translational thinking, neurobiology of RNA regulation, and the emerging role of biomolecular condensates in disease, contributing to the long-term goal of developing targeted approaches for idiopathic ASD.

Autism spectrum disorder, CPEB4, biomolecular condensation, translational science

Functional characterisation of CD98hc isoforms in cell viability, plasticity and cancer

https://www.irbbarcelona.org/en/research/amino-acid-transporters-and-disease

"Amino acid transporters are essential regulators of cellular metabolism, growth and adaptation, as they control the uptake of nutrients required for protein synthesis, energy balance and signalling. In mammalian cells, L-type amino acid transporters (LAT family) play a particularly important role in supporting metabolic flexibility, especially in highly demanding contexts such as cancer. Many LAT transporters require the auxiliary subunit CD98hc (SLC3A2), a multifunctional protein that links amino acid transport to redox homeostasis, integrin-dependent signalling and cell survival.

Recent evidence indicates that the human SLC3A2 gene expresses multiple CD98hc isoforms that differ in their cytoplasmic N-terminal region. Some of these isoforms appear to be selectively enriched in cancer cells; however, their functional role has not yet been described in the literature. Understanding whether these isoforms contribute to cell viability, metabolic adaptation and cellular plasticity represents an important open question with potential translational relevance.

This Master’s Thesis project aims to study the function of novel CD98hc isoforms using experimental cell-based approaches. Isoform-specific modulation can be achieved using CRISPR-based knockout strategies and gene silencing approaches, and the effects on cell viability, plasticity and cancer-related phenotypes can be analysed. Depending on the student’s interests, the project can also be adapted to explore related amino acid transporters or complementary functional readouts.

The work will be carried out in a laboratory with extensive expertise in amino acid transporters, combining cell biology, biochemistry and structural approaches. The student can receive training in advanced cell culture, molecular biology, protein expression and purification, and functional assays to study amino acid transport. This multidisciplinary project offers broad experimental training, strong conceptual foundations, and the opportunity to contribute to an original and flexible research topic at the interface of metabolism and cancer biology."

Amino acid transporters, CD98hc (SLC3A2) isoforms, Cellular plasticity, Cancer metabolism, CRISPR-based functional analysis

www.irbbarcelona.org

Our labo has recently discovered that mutant tRNAs accumulate with human aging. This process leads to the emergence of chimeric tRNAs in cells that introduce generalized errors in the proteome. We now need to characterize the molecular aspects of this phenomenon, and study to what extent it can be prevented. This is a unique opportunity to study a new aging mechanism of very high potential impact. We seek imaginatiuve and ambitious students that may be interested in continuing towards a PhD degree.
for more info see: bioRxiv 2025.06.09.658696

Investigating the frequency-dependent mechanics of splicing condensates and their cellular environment

https://livinglight.icfo.eu/

Fundamental cellular events such as axonal transport and synaptic transmission, but also the distribution of genetic material among dividing daughter cells depend on cytoskeletal activity. The activity of actin and microtubule filaments produces active forces that mix the cytoplasm and agitate membrane-bound organelles including the nucleus in both somatic and germ cells. These forces are transmitted into the nucleus but their functional impact on intra-nuclear biology has been overlooked, with intracellular mechanical activity long presumed too weak to influence gene regulatory mechanisms. The Al Jord lab (CRG) has recently identified that cytoskeletal fluctuations are critical for RNA splicing reaction and gene regulation to take place.

The nucleus’ interior and cytoplasm behave as viscoelastic materials with different mechanical properties. When these two components are mechanically coupled, the resulting system can be approximated by Jeffrey’s model, combining both elastic and viscous elements. This composite material theoretically creates a frequency-dependent force transmission profile. In brief, this model predicts a permissive frequency range, where elastic behavior dominates at certain frequencies enabling more efficient force transmission. Outside this window, in the restrictive frequencies, viscous dissipation dominates, limiting mechanical coupling and functional impact.

We hypothesize the existence of a selective frequency window in which force transmission across the cyto/nucleoplasm is maxmimized.

Our hypothesis is that each cytoskeletal and nuclear compartment may possess a distinct permissive frequency range shaped by its composition, architecture, and biophysical properties. Identifying these frequencies is critical for understanding how mechanical forces regulate gene expression and how mechanical perturbations contribute to disease.

Objective:
To resolve mechanical responses across timescales, we will use optical tweezers, which employ a tightly focused laser to trap and manipulate micron-scale probes with piconewton force sensitivity. We recently developed an active microrheology approach that directly quantifies the frequency-dependent mechanical properties of intracellular environments in living cells. In this method, a bead confined in the optical trap is driven by a precisely controlled oscillatory force spanning 0–2000 Hz, while its displacement is recorded in real time. The bead’s response captures the crossover from viscous- to elastic-dominated behavior, defining the frequency band in which mechanical energy transfer is most efficient and the material is maximally mechanoresponsive, enabling optimal force transmission.
As an initial application, we will use this framework to determine the permissive frequency window of splicing condensates and of the surrounding nucleoplasm-like medium. In collaboration with the Al Jord lab, we will then test how this mechanically defined frequency regime modulates splicing reactions, both in reconstituted systems in vitro and in living cells in vivo.

Cytoskeletal forces, Mechanobiology, Nuclear condensates, RNA-processing, rheology, Optical tweezers

https://ibecbarcelona.eu/ca/molecular-bionics/

Alzheimer’s disease (AD) affects around 50 million people worldwide. Despite tremendous efforts to develop effective treatments, clinical success has been limited. This underscores the urgent need for a deeper mechanistic understanding of the disease.
This project aims to investigate the early stages of neuronal degeneration in AD, with a particular focus on the initial solid transition of amyloid-β (Aβ) using live-cell imaging approaches. Aβ is one of the two hallmark proteins that aggregate in the brains of individuals with AD. However, the dynamics of Aβ’s initial solid transition within neurons, and its immediate effects on neighboring cellular structures, remain poorly understood.
Briefly, we will combine in vitro reconstitution assays with neurons derived from human pluripotent stem cells (hPSCs) to study the initial solid transition of Aβ and its consequences for neuronal function in a mechanistically detailed manner.
We are looking for a motivated and curious student, ideally with a background in Cell Biology, Biochemistry, or Biomedicine. The student will receive training in the differentiation of hPSCs into cortical neurons and spheroids. They will learn fluorescence-based imaging techniques to analyze Aβ solid transitions and assess their impact on neuronal function. The student will also gain experience in in vitro reconstitution approaches, as well as molecular biology techniques such as Western blotting, immunostaining, and semi-automated image quantification and data analysis.

Alzheimer's Disease, Neuronal Degeneration, Solid Transition, Amyloid beta, hPSCs

Lung-in-a-Dish Macrophages: Building renewable human alveolar macrophage models from iPSCs

https://ibecbarcelona.eu/molecular-bionics/

Resident macrophages (rMɸs) are deeply influenced by the stimuli of the tissue where they are located. Local signals imprint their identity, modulating how they sense intruders and coordinate inflammation. Yet, despite their relevance in regulating tissue homeostasis, we are still lacking an accessible in vitro system that closely recapitulates the phenotypic diversity of rMɸs. This gap limits our ability to dissect rMɸs biology and to study host responses under physiologically relevant conditions.

For instance, in the lungs, rMɸs specialization is especially relevant because lung rMɸs, referred to as alveolar macrophages (AMs), must constantly balance immune vigilance with tolerance to harmless environmental exposure. This highlights the need to develop a robust human in vitro platform that better emulates rMɸs' innate immune functions and tissue-specific programming.

In this project, we will establish a human, lung-relevant macrophage model that will enable the study of resident-like AMs behavior in a controlled setting. We will generate a renewable cell source by deriving induced pluripotent stem cells (iPSCs) from primary human lung fibroblasts and using these cells to produce iPSC-derived macrophages (iMACs). iMACs will then be guided towards an AMs state by exposure to key lung-associated cues, with the final aim of promoting features typical of lung rMɸs. Throughout the project, we will track the differentiation trajectory using a defined set of established identity markers and phenotypic readouts, ensuring that each transition follows the intended path.

Overall, this work will deliver a standardized and scalable in vitro platform to model human AMs biology. By providing a closer approximation of tissue-programmed macrophages than conventional systems, this platform will support future studies of lung innate immunity, including mechanisms of inflammation, host–pathogen interactions, and strategies aimed at macrophage reprogramming for therapeutic benefit

Human in vitro lung model, Stem cell–derived macrophages, Tissue-resident immunity

Engineering Phosphorylcholine-Based Block Copolymer Nanoparticles for Targeted Modulation of Inflammation

https://www.molecularbionics.org/

Chronic inflammatory diseases account for more than 50% of global mortality, contributing to conditions such as stroke, cancer, diabetes, etc. While inflammation is a natural protective response, its dysregulation leads to persistent tissue damage and disease progression.
Conventional anti-inflammatory therapies often result in severe side effects, poor selectivity, high costs, and limited long-term efficacy. Nanomedicine offers a powerful alternative by overcoming these limitations and enabling selective targeting of specific cell populations. In particular, macrophages, central regulators of inflammation, represent an attractive therapeutic target to modulate inflammatory processes at their source. Phosphorylcholine (PC), a zwitterionic motif naturally present in cell membranes, has demonstrated strong potential as a macrophage-targeting ligand. PC-bearing nanoparticles promote receptor-mediated internalization and may influence signaling pathways involved in inflammatory resolution.
The aim of this project is to design and synthesize PC-bearing block copolymers that self-assemble into nanoparticles capable of selectively targeting macrophages and modulating inflammatory responses. Living polymerization techniques will be employed to prepare polymers with controlled structure and molecular weight, enabling precise tuning of nanoparticle size, morphology (micelles, polymersomes, or related nanostructures), and surface chemistry. The multivalent presentation of PC units will be explored to enhance ligand–receptor interactions through avidity, ultimately optimizing anti-inflammatory performance.
We seek a motivated and curious student with a background in Chemistry, Biochemistry, or Biomedicine and a strong interest in polymer chemistry and nanomaterials. As part of a multidisciplinary research group, the student will be involved in different aspects of the project: (a) polymer synthesis and characterization (gaining experience in living polymerization, NMR and gel permeation chromatography); (b) nanoparticle self-assembly and physicochemical characterization (learning about dynamic and static light scattering and electron microscopy); and (c) in vitro evaluation of anti-inflammatory activity of the nanoparticles (being trained in cell viability, internalization, and functional assays).

Phosphorylcholine, Block Copolymers, Living Polymerization, Macrophage Targeting, Nanomedicine

Complementing shotgun sequencing with long-read sequencing for reconstructing the genomes of the microbes inhabiting the gut

https://www.crg.eu/en/programmes-groups/baud-lab

Bigger project the internship project fits in:
As part of our research on host-microbiome interactions, we have profiled the gut microbiome of thousands of genetically diverse laboratory rats using deep shotgun (Illumina) sequencing. The same rats were also genotyped and extensively phenotyped by our American collaborators. The overarching goal of this large-scale project is to understand how the genetics of the rat host shapes the gut microbiome and how the composition and functional potential of the gut microbiome influence the rat host’s phenotypes, which are all measures relevant to human diseases (see ratgenes.org).

Problem statement:
To be able to characterise the composition and functional potential of these microbiomes, we need a good database of microbial genomes to map the reads to. Current databases include very little rat microbiome data. Hence, we need to improve these databases by generating a complete catalogue of the genomes of the microbes present in the rat gut (catalogue of metagenome-assembled genomes = MAGs). A postdoctoral fellow who will start working in our lab in May will work on building this catalogue using extra-deep shotgun sequencing data that we have collected on a separate, very diverse set of rats (rats from different locations, ages, etc.).

Internship project description:
The main objective of this proposed project is to support this effort using long-read (nanopore) sequencing data generated from the same rat gut microbiomes. The integration of shotgun and long-read sequencing data is expected to greatly improve the quality and quantity of the microbial genomes that can reconstructed.
The project will be purely computational as the long-read sequencing data are being generated by the CRG’s core sequencing facility.
The internship student will be co-supervised by the group leader and the postdoctoral fellow, with support from the CRG’s core bioinformatics unit or other research groups if needed to analyse the long-read data (there is a lot of expertise on this topic at the CRG).

Expected impact of the project and associated publication:
The results of this project will help improve public databases, giving it broad impact on the biomedical research community. For our lab’s specific research, it will provide an essential resource (MAG catalogue) for all future microbiome projects.
In terms of publications, I expect a unique publication on the rat MAG catalogue that will be generated based on the integration of the shotgun and long-read sequencing data.

Preferred profile of the internship student:
The Master’s student applying for this internship should be very familiar with the analysis of genome sequencing data (shotgun and/or long-reads), ideally having demonstrable practical experience working with them (e.g. hackathons, previous internships,…).
Previous experience with high performance computing environments is also preferred.
Finally, knowledge and an interest in the microbiome is also preferred.

The internship will be remunerated.
The student is expected to work in the lab at least four days a week (one day remote could be allowed).
There is a possibility to continue in the lab as a PhD student after the internship, funding permitting.

Glycoengineering the Blood-Brain Barrier to Understand Therapeutic Delivery to the Brain

https://ibecbarcelona.eu/molecular-bionics/

The blood-brain barrier (BBB) is a highly specialized vascular structure crucial for proper neuronal function by tightly regulating the molecular transport between the bloodstream and the brain. However, due to its selective permeability, the BBB also represents a major challenge for therapy delivery to the brain. Accumulating evidence indicates the BBB glycocalyx, a dense mesh of sugars (glycans and glycoconjugates) which coats the surface of the brain vasculature, plays a central role in modulating transport across the BBB. However, relatively little is known about how the glycocalyx structure (i.e. specific sugar patterns) impacts the rate and specificity of transport into the brain.
To address this limitation, the current project will develop strategies to engineer the glycocalyx composition in isolated BBB (endothelial) cells. Employing microfluidic systems, the glycoengineered BBB models will be employed to assess the impact of glycocalyx structure on endocytic transport mechanisms responsible for delivery of therapies into the brain. This project will therefore increase our understanding of how regional variations in BBB glycocalyx determines brain uptake and how disease-related glycocalyx modifications impacts therapy delivery, thereby serving to increase the delivery specificity of therapies against neurological disorders.
We are seeking a motivated student seeking to work on:
• development of ‘Organ-on-Chip’ technologies for modelling the BBB
• enzymatic and genetic manipulation of cell-surface glycan composition
• confocal microscopy, immunocytochemistry and cell-uptake assays to track molecular transport across the BBB
• ‘Omic’ analysis of protein and glycan structures at the BBB
Through these techniques, the student will learn:
• Microfabrication and assembly of BBB models
• Cell culturing (immortalized cell lines; direct extraction from rodents)
• Nucleic acid transfection
• Fluorescence-based macromolecular uptake/endocytosis assays
• Quantitative data analysis

Candidate Profile:
Students in biomedical sciences, biotechnology, bioengineering, or related fields.

Blood-Brain Barrier, Glycocalyx, Glycoengineering, Endocytic transport, Therapy Delivery

Plasma membrane tension: a new mechanism that regulates information flow at the cell surface?

https://www.icfo.eu/research-group/21/smb/home/

The plasma membrane of cells is mainly composed of lipids and proteins that separate the interior of the cell from its external environment. Interactions between specific lipids and proteins drive the lateral organization of the membrane, dynamically forming nanoscopic regions (nanoclusters) with different properties. These nanoclusters play a crucial role in essential cellular functions such signal transduction, trafficking, adhesion, motility, and many other cellular functions. As such our Lab recently proposed that nanoclusters behave as nanohubs of activity that regulate information flow at the plasma membrane. Research over the last years, including key contributions from our Laboratory have elucidated different molecular mechanisms responsible for the nanoscale organization of the plasma membrane. Yet, how tension at the plasma membrane impacts in the organization of receptors at the nanoscale, their activation and signalling remain totally unknown.

While traditionally considered a uniform property of the plasma membrane, recent theoretical models have suggested that the tension at the plasma membrane can be compartmentalized in spatial heterogeneous regions, whose existence depends on the underlying actin cortex and is influenced by lipid composition. Such physical mechanism could provide the means to spatiotemporally regulate the architecture of the plasma membrane. However, direct experimental validation of such compartmentalization in living cells remains limited.

The goal of this project is to investigate whether membrane tension is compartmentalized in space and time and its role regulating receptor organisation and downstream signalling for appropriate cell response. For this, we will rely on the use of recently developed mechano-fluorophores (Flipper-TR) combined with fluorescence lifetime imaging microscopy (FLIM) and super-resolution STED microscopy. The project will involve extensive time-lapse high-resolution imaging of Flipper-TR, quantitative analysis and different pharmacological approaches to elucidate the role of lipid composition and membrane-cortex attachments modulating the degree of membrane tension propagation in living cells.

membrane tension, biological membranes, photo-active molecules, super-resolution fluorescence microscopy

Enabling live cell nanoscopy imaging of individual molecules under mechanical forces.

https://www.icfo.eu/research-group/21/smb/home/

Cells in our body are subjected to mechanical forces generated by the extracellular environment and intracellular processes. Their ability to detect, apply and transmit forces is critical for the correct function of fundamental cellular events, which is achieved by a complex machinery of mechanosensitive structures that operate with exquisite precision at the molecular level. During the last years, smart methods and tools have been developed to generate and quantify forces in cells at different spatiotemporal scales, however, visualizing the effects of mechanical forces on individual molecules in living cells remains particularly challenging.

Our laboratory, in collaboration with the group of Pere Roca-Cusachs in IBEC, is currently developing and applying an innovative cell mini-stretching system that enables the simultaneous application of forces while imaging the organization and interactions of mechanosensitive proteins at the nanoscale. Specifically, our cell stretching devices now allow live cell imaging and are fully compatible with a super-resolution fluorescence microscopy technique called STED (Stimulated Emission Depletion Microscopy). Our device is a powerful and unique tool with tremendous potential for unveiling the nanoscopic secrets of cell mechanobiology.

The goal of the project is to investigate the role of mechanical forces on the nanoscale organization, activation and signalling of key cell membrane mechanosensitive proteins using STED super-resolution microscopy in combination with mini-stretching devices.

In terms of specific objectives: 1) To optimize the conditions for both cell stretching and super-resolution imaging experiments using different stretching schemes and force loads that cells tolerate and explore several fluorescent molecules suitable for one colour and two-colour STED. 2) To perform simultaneous cell stretching and nanoscopic imaging to characterize the effects of external forces on the mechanosensitive proteins. 3) To provide quantitative descriptions on how mechanical forces impact on the nanoscale organization and activation of different integrin receptors and their adaptors.

mechanobiology, super-resolution microscopy, cell stretching, protein nanoscale organization

A Multiscale Approach to Alzheimer’s Inhibition: Correlating In Silico Amyloid-β 42 Fibril Trajectories with In Situ Liquid Phase TEM

https://ibecbarcelona.eu/molecular-bionics/

"Project Overview
Amyloid-β (Aβ) peptides self-assemble into ordered fibrils, which are the main pathological features of Alzheimer’s disease. These fibrils serve as persistent structural scaffolds that recruit surrounding peptides, leading to local toxicity and disease progression. This multidisciplinary project explores the physical principles behind fibril inhibition by comparing two fundamentally different strategies: the FDA-approved monoclonal antibody Lecanemab, which uses sequence-specific molecular recognition, and an in-house PEG–PLA block copolymer, which employs multivalent, amphiphilic surface adsorption.
Objectives and Methodology
The study aims to compare how highly specific, localised binding versus more diffuse adsorption affects Aβ42 stability and interface dynamics. Using GROMACS, high-resolution molecular dynamics (MD) simulations will be conducted on cryo-EM-derived Aβ42 segments. Three systems will be built and analysed: a fibril control, a fibril-antibody complex, and a fibril-polymer assembly, to map residue-specific contact persistence, β-sheet hydrogen-bond occupancy, and interfacial water density at the atomic level.
Bridging the Gap with Liquid Phase TEM
A key feature of this project is the use of Liquid Phase Transmission Electron Microscopy (LP-TEM). While simulations deliver atomic detail, LP-TEM allows visualisation of these systems in solution under near-physiological conditions at the nanoscale. This advanced technique provides real-time, complementary information on structural and dynamic changes. By correlating computational trajectories with in situ experimental imaging, you will develop a comprehensive understanding of how different chemical architectures influence protein aggregation.
Training and Impact
As a Master’s student, you will gain extensive training in PDB handling, MD simulation protocols, and advanced microscopy techniques. This project sits at the intersection of computational biophysics, imaging science, protein dynamics, and experimental nanotechnology, laying a strong foundation for future careers in drug discovery and materials science. You will contribute to elucidating the physical mechanisms essential for designing the next generation of Alzheimer’s therapies."

Amyloid-β 42 Fibrils, Molecular Dynamics Simulations, Liquid Phase TEM , Alzheimer’s Therapeutics, Protein-Inhibitor Interactions

https://phpb.icfo.eu/#about

Plants rely on Nonphotochemical Quenching (NPQ) to dissipate excess excitation energy and prevent photodamage. This process is triggered by lumen acidification, which initiates different photoprotective responses in the thylakoid membrane. A central step consists in the conversion of the carotenoid violaxanthin into zeaxanthin catalysed by the enzyme called Violaxanthin De-epoxidase (VDE). Although it has been shown that zeaxanthin alone is not sufficient to sustain NPQ, it has been proposed that it is essential for enhancing quenching. Despite its importance, the molecular mechanism of VDE activation remains poorly understood. Key aspects, including the roles of the N- and C-terminal domains on the oligomeric state, catalytic activity and interaction with the membrane, remain largely fragmented. This project aims to investigate the mechanistic basis of VDE activation using a multiscale computational approach. To do that, we will employ a multiscale computational approach combining molecular modelling, atomistic and coarse-grained molecular dynamics simulations, enhanced sampling techniques, and free-energy calculations. Depending on the specific direction of the project, the work may involve the characterization of VDE conformational dynamics, protonation-dependent activation mechanisms, protein–membrane interactions, substrate binding and transport, or interactions with photosynthetic membrane components. Overall, the project aims to provide a mechanistic understanding of VDE function within the broader context of photosynthetic photoprotection, while contributing to the development and application of advanced computational strategies for studying complex membrane-associated biological systems.

plants, photoprotective response, molecular modelling, multiscale computational approach