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Cell Culture:

What are colonies?

Why do they matter?

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Bacteria are

  • Highly diverse
  • Simple, small, single-celled organisms with short generation time
  • Prokaryotic cell (not the same organelles as the eukaryotic cells)
    • Nucleoid (mass of DNA and plasmids)
    • Cell walls
    • Some have slime layers (preventing infections, phagocytosis and desiccation.
    • Flagella (for movement)

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Yeasts are

  • Single-celled organism
  • Fungus
  • Live together in multicellular colonies with a rapid division rate
  • Eukaryotic cells (has nucleus and other membrane-bound organelles)
    • More rigid than bacterial cells membrane
    • Cell wall (protective structure!)

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The importance of classification to microbiology

Microbes and other single celled organisms are classified and identified to distinguish them from other similar organisms by using specific criteria. The most important level of classification is the name of a species which need to be recognized consistently by all scientists.

Some of the things classification is based on are:

  • Similar physiological characteristics
  • Genetic traits
  • Phylogenetic markers

The science of naming and classifying organisms is called taxonomy and its based on organisms with similar characteristics, like the phylogenetic trees you saw on the last slide!

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Taxonomy

Taxonomists use a structural hierarchy

  • Groups are nested based on characteristics
  • Highest level is general and progressively get more specific as you get to the lower levels
  • Each group is called a taxon, most general taxon is a species

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Levels of classification

The common classification system has 8 levels of taxa; domain, kingdom, phylum, class, order, family, genus and species.

  • These are all nested within each other

Domain: Highest rank in biological classification (see example image below)

  • Three domains; Archaea, Bacteria and Eukarya

Kingdom: Second level in biological classification.

  • Six Kingdoms: Archaea, Bacteria, Protista, Fungi, Plantae, and Animalia.

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Levels of classification

Phylum: Third rank in biological classification.

  • Based on general body structure, e.g. Chordata have internal skeletons, and backbones/notochord.

Class: Fourth level in biological classification.

  • These share more characteristics with each other than other organism e.g. Frogs (Amphibia, moist skin and jelly-like eggs) vs. Snakes (Reptilia, dry skin and leathery eggs).

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Levels of classification

Order: Fifth level in biological classification.

  • This level shares even more traits! E.g. Humans and cows are both mammals but they belong to different orders because of their traits. Cows are in the order Artiodactyla (cows, pigs, giraffes) due to their hooves. Humans are primates (like monkeys and apes) because they have forward facing eyes and have depth perception because of it.

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Levels of classification

Family: Sixth level in biological classification.

  • This level shares even more traits! E.g. the Order Carnivora has foxes, otters and coyotes but foxes and coyotes also belong to the Family Canidae! Whereas otters belong to the Family Mustelidae.

Genus: Second last level in biological classification.

  • This level shares structural similarities and are more closely related. E.g. the cat family has house cats, lions, bobcats and tigers. But the lions and tigers are more closely related! They belong to the genus Panthera!

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Levels of classification

Species: The last level in biological classification.

  • This level shares even more traits! You are likely familiar with species as they are commonly known! Members in the same species share their evolutionary history and are more closely related than any other organisms. This classification is based on physical and genetic similarities.
    • Species share the same number of chromosomes!

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Species

Species: Important criteria!

  • Producing viable offspring!
    • This means that when they mate they produce offspring that can in turn produce more offspring!
    • Sometimes other species are able to reproduce, however, their offspring is sterile! Meaning they can not reproduce.
      • Classic example is a horse and a donkey! This produces a mule- which are sterile!

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Species

Species: Important criteria!

  • Producing viable offspring!
    • This means that when they mate they produce offspring that can in turn produce more offspring!
    • Sometimes other species are able to reproduce, however, their offspring is sterile! Meaning they can not reproduce.
      • Classic example is a horse and a donkey! This produces a mule- which are sterile!

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Classification in Microbiology

Due to the small size of bacteria and the visual appearance being similar by the naked eye there are different classification techniques needed!

  • DNA Sequencing
  • Gram Staining
  • Morphology and physical characteristics

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What are colonies?

  • A colony is a group of microorganisms—like bacteria or fungi—that grow together on a solid surface or medium. These tiny organisms start from a single parent cell and multiply to form a visible “mound” or mass.

  • Colonies aren’t just clusters of cells—they work together to survive! They can protect themselves, compete for food, and communicate with each other to adapt to their environment.

  • Unlike multicellular organisms, colonies don’t have specialized organs or structures. Each cell handles its own metabolism and reproduction. However, being part of a colony can still influence reproduction through a process called quorum sensing (more on that later!).

Each of these round dots are colonies of e. coli!

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Why do organisms form colonies?

  • Microorganisms, like bacteria, form colonies to gain a competitive edge, stay healthy, and communicate with one another.

  • Through communication, they can prevent overgrowth, which happens when too many cells grow on the same surface. Overgrowth can lead to a shortage of food and resources for everyone!

  • By working together to control growth, colonies improve their chances of survival, ensuring they have enough resources to thrive.

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How do colonies communicate?

  • Colonies communicate with each other using a process called quorum sensing (QS).

  • Through quorum sensing, colonies send chemical signals called autoinducers to “talk” to one another. These signals help them coordinate important activities, like regulating gene expression and controlling their population size.

  • This teamwork ensures the colony stays balanced and can survive in its environment!

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How do autoinducers participate in QS?

  • Autoinducers are chemical signals made by individual cells. In gram-negative bacteria, they can passively diffuse out of the cell (this process doesn’t use energy).
  • As more autoinducers are released, they build up outside the cells. Once their concentration reaches a critical point, the cells “decide” they’ve sent enough signals. At this stage, the autoinducers bind to specific receptors, triggering a chain reaction that changes gene expression and controls population size.

What is gram negative vs positive?

Gram-positive bacteria have a thicker outer membrane than gram-negative bacteria have.

What qualifies as an autoinducer?

    • It’s produced during certain growth phases.
    • It diffuses and accumulates in the environment.
    • It binds to a specific receptor when it reaches a threshold.
    • The resulting changes improve cell survival (e.g., better metabolism, detoxification, or controlled growth).

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How do you identify colonies?

Colony formation isn’t just fascinating—it’s also a key tool for scientists! By observing a colony’s visual characteristics, scientists can figure out what organism is growing.

Some common features used to identify colonies include:

  • Shape (round, irregular, etc.)
  • Color (white, yellow, pink, etc.)
  • Size (small, large, or somewhere in between)
  • Surface appearance (smooth, shiny, wrinkled, or dull)
  • Texture (soft, rough, or firm)

These traits make it easier to identify and study different microorganisms!

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Spot the Differences!

Take a look at these two cultures—they’re from different species. Can you identify the differences in their characteristics? Look closely at features like shape, color, size, surface appearance, and texture!

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Bacteria Characteristics: K-12 E. coli

  • Natural Habitat: Normally found in the intestines of mammals.
  • Culture Temperature: Grows best at 37℃.
  • Doubling Time: Reproduces every 30 minutes.
  • K-12 Strain: A lab-safe version of E. coli, engineered to survive only in specific conditions. It’s one of the most widely studied organisms in science!
  • Gram-negative bacteria

Physical Characteristics of Non-Transformed K-12 E. coli in Culture:

  • Size: 1-3 mm
  • Surface: Smooth (may become rough with repeated subculturing)
  • Color: Grayish white
  • Shape: Circular
  • Appearance: Translucent to opaque

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Bacteria Characteristics: K-12 E. coli

Can you guess why the culture temperature is 37℃?

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Fungi Characteristics: Saccharomyces cerevisiae (Baker’s Yeast)

  • Natural Habitat: Commonly found in bakeries and breweries, yeast is one of the first domesticated organisms!
  • Culture Temperature: Grows most rapidly at 30℃.
  • Temperature Range: Can grow between 25℃ and 47℃.
  • Doubling Time: Reproduces every 90 minutes.
  • Normally gram-positive but can stain as negative if it is in bad health

Physical Characteristics of Non-Transformed S. cerevisiae in Culture:

  • Surface: Moist/slimy (some strains may appear dry and wrinkled).
  • Color: White to cream-colored.
  • Texture: Rough or smooth.
  • Size: 1-2 mm after 28 hours.

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Fungi Characteristics: Saccharomyces cerevisiae (Baker’s Yeast)

Did you know that yeast grows on the surface of fruit? This is why breweries have to sterilize their fruit juices before they inoculate with their own alcohol-producing yeast!

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Fungi Characteristics: Yeast

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More on Colony Characteristics

Microorganisms can have diverse colony characteristics, also known as their colony phenotype. Here are some key features to observe:

  • Shape: Colonies may appear irregular, filamentous, or rhizoid.
  • Size: Measured in millimeters, colony size varies depending on the species and growth conditions.
  • Edge: The borders of a colony can be smooth, wavy, or jagged. These edges are often easier to observe under a microscope but can also be noticeable in larger colonies.

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More on Colony Characteristics

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More on Colony Characteristics

Microorganisms exhibit a variety of colony phenotypes. Here are some additional features to observe:

  • Color (Chromogenesis):
    • The color of the colony may vary based on the microorganism.
    • Factors like the growth medium, temperature, or whether the entire colony has the color can influence pigmentation.
  • Opacity: Can be transparent (clear), translucent (partially clear), opaque (not clear), or even iridescent.
  • Elevation: Check how “tall” the colony rises from the surface of the agar.
  • Surface: Look for textures like smooth, glistening, rough, dull, or wrinkled.
  • Texture: Colonies might feel buttery (butyrous), sticky (viscid), brittle , or mucoid (slimy, like mucus).

Understanding these traits helps scientists identify and study different microorganisms

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Identifying Characteristics: Practice

Take a closer look at the physical characteristics of the cells on the petri dishes on the next slides. Fill in the details based on your observations:

  • Shape: What overall shape does the colony have (e.g., circular, irregular)?
  • Side View: Observe the elevation—how tall or flat does the colony appear from the side?
  • Texture: How does it feel or look (e.g., buttery, sticky, brittle, or mucoid)?
  • Surface: Is the surface smooth, rough, shiny, dull, or wrinkled?
  • Size: Measure the colony’s diameter in millimeters.
  • Color: What is the pigmentation? Is it white, cream-colored, or something else?

Use these characteristics to practice identifying and describing colonies!

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Identifying Characteristics: Practice

Take a closer look at the physical characteristics of the non-transformed yeast strain. Fill in the details based on your observations:

Shape:

Side View:

Texture:

Surface:

Size:

Color:

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Identifying Characteristics: Practice

Take a closer look at the physical characteristics of this transformed (engineered) bacteria strain. Fill in the details based on your observations:

Shape:

Side View:

Texture:

Surface:

Size:

Color:

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Another way to differentiate bacteria is gram staining which works by exploiting the differences in their cell walls. This can be used with other methods to identify bacteria (like molecular techniques i.e. PCR, quantitative PCR, genome sequencing and mass spectrometry).

Gram staining allows identification by:

  • Shape
  • Some phenotypic differences
  • Cellular arrangements

This places microbes into a broad group which can narrow down the possible identity of the organisms.

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Gram-staining is useful to identify the structure of bacterial cell walls. The walls of cells will color differently depending on if they are positive or negative. Positive cells will be a purple or blue and negative will be pink or red!

However, this can also be used on other microbes! Like yeast!

Yeast cells (Candida albicans (left) and candida spp. (right)) gram stained.

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Gram-positive bacteria have a thick peptidoglycan cell wall and have no outer lipid membrane. These are called monoderms. These bacteria are typically staphylococci, streptococci and some listeria species.

The structure of the walls affect the cells ability to retain the crystal violet that is used for gram staining. This is because the peptidoglycan retains it!

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Gram-positive bacteria retain the complex that is created by the primary stain crystal violet and iodine. This binds to this negatively charged membrane (charge due to the presence of phosphodiester bonds between teichoic acid monomers) because this dye is positively charged. The iodine traps this crystal violet so it cannot be removed, this is termed a mordant! This complex is strong enough to stay even after they are washed with water or alcohol! The alcohol is termed a decolorizer in this procedure and will also remove the complexes from the gram-negative cells. These cells have 20% of their cell wall made of peptidoglycan so they are unable to retain the crystal violet and iodine complex. This is in comparison to the 80% composition of the peptidoglycan in the cell wall of gram-positive bacteria.

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Gram-negative cells will color pink and this is because of the counterstain called safranin! This is another positively charged dye which binds to the cell membrane.

The safranin binds to both types of cell but the crystal violet and iodine complex causes a different color (the dark purple or blue).

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Gram-negative bacteria have a thin peptidoglycan cell wall and they also have an outer layer membrane containing lipopolysaccharides. These cells are called diderms. These bacteria typically include enterobacter species, salmonella, escherichia and pseudomonas.

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Gram-negative bacteria have a thin peptidoglycan cell wall and they also have an outer layer membrane containing lipopolysaccharides. These cells are called diderms. These bacteria typically include enterobacter species, salmonella and pseudomonas.

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Gram staining: Gram-positive bacteria vs Gram-negative bacteria

Gram staining has limitations because it does not actually allow you to reliably assess the phylogenetic relationships. This is because of convergent evolution, the second membrane characteristic of gram negative bacteria evolved many times over different lineages.

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The Importance of Sterility in Cell Culture

Microorganisms love their growth media, like YPD agar for yeast and LB agar for E. coli—but so do other unwanted organisms! That’s why maintaining sterility is crucial to avoid contamination.

While E. coli and yeast are hardy and can often grow even with some contamination, other cell lines can be much more sensitive. In some cases, contamination can wipe out an entire culture. Even worse, accidentally growing harmful organisms can pose serious risks.

To stay safe and protect your experiments, always deactivate contaminated plates. Use bleach and an inactivation bag to safely dispose of them. Need help? Check out our instructions on how to deactivate plates!

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The Importance of Colonies in Genetic Engineering

Colonies play a crucial role in genetics research and biotechnology. They allow scientists to introduce new genes into bacteria for various purposes, like studying gene function or producing valuable proteins.

A key reason colonies are so important is their growth phase! After hours of culture, colonies enter the log phase (or exponential phase), where cells reproduce quickly and are at their healthiest. This is the ideal stage for cell transformation.

If cells move beyond this phase, they may begin to burst or die, reducing the chances of a successful transformation. Older cells are also more vulnerable to DNA damage, making them less reliable for genetic engineering.

By working with colonies, scientists ensure that cells are in the same growth phase, which helps avoid contamination and improves the consistency and success of their experiments!

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Steps to Growing and Identifying Colonies

1

Scientists start by preparing growth media, which is often selective to minimize contamination. Different microorganisms need specific “food,” so the media is tailored to their unique requirements.

Preparation of growth media

Streaking the organism

Next, scientists streak their organism onto the media—either re-streaking from a previous culture or using a stab. There are various streaking methods to maximize colony formation, and we’ll explore a few later!

2

3

4

Microorganisms grow at different rates and temperatures, so it’s essential to incubate them under the right conditions for optimal growth.

Microorganism incubation

After incubation, colonies should appear on your plate! Instead of long streaks, the colonies will look like small, dot-like formations.

Colony formation!

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Example: Streaked Magenta E. coli

What is a Lawn?

A lawn is a dense, continuous growth of cells spread across the surface of the agar plate. It needs to be diluted using inoculation loops to isolate individual colonies. In the figure on the right, A shows an example of a lawn.

What Does a Colony Look Like?

A colony is a small, dot-like cluster of cells that forms when individual cells grow and divide in isolation. Colonies are typically obtained through streaking techniques. In the figure on the right, B shows an example of a colony.

A

B

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Example: Streaked Cyan S. Cerevisiae

Example Organism: Saccharomyces cerevisiae, genetically engineered to fluoresce green and resist G418.

Culture Conditions: Grown on G418-selective YPD agar at 30℃.

Steps:

  • Select a Colony: Start by picking a colony from plate 1.
  • Create a Lawn: Use the selected colony to create a dense lawn of cells (A).
  • Streak for Colonies: Use a streaking pattern to dilute the cells and form isolated colonies (B).

Plate 1

Plate 2

B

A

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Why Use Streaking Patterns?

Streaking patterns dilute the cells to lower concentrations, allowing individual colonies to form. An example streaking pattern is shown on the stencil. This is called the four-quadrant pattern.

This is an example of the four-quadrant streaking method!

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Beyond Temperature: Key Factors for Successful Cell Incubation

Humidity

Humidity is crucial for preventing the evaporation of growth media. Higher humidity helps keep your cell growth media (often with a jell-o-like texture) from drying out, ensuring the cells have the moisture they need to thrive.

Air Composition

  • CO₂ Levels: Maintaining 5% CO₂ in the incubator is essential.
  • Why It’s Important: CO₂ helps regulate the pH of the culture medium, keeping it stable and optimal for cell growth.

Proper humidity and air composition, alongside temperature, are key to creating the perfect environment for your cells to grow!

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Beyond Temperature: Key Factors for Successful Cell Incubation

Not all incubators are equipped with advanced components to regulate air composition and humidity—but don’t worry! There are simple and effective ways to manage these factors:

Invert Your Plates: Flip your plates upside down to prevent condensation from forming on the lid. Condensation can lead to water dripping onto your culture, which may compromise its growth.

Use a Humidity Chamber: Placing a humidity chamber over your petri dish helps minimize moisture loss from the agar, keeping your culture in optimal condition.

These easy adjustments ensure successful results, even with basic incubator designs!

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The Streak-it Kit Experiment

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Your Experiment

In this experiment, you’ll use the Streak-it Kit to:

  • Learn how to streak and culture two pre-genetically engineered organisms (yeast and bacteria).
  • Obtain colonies and use them to form a data-driven hypothesis.
  • Practice different streaking strategies to isolate colonies.
  • Learn how to obtain a pure culture.

This experiment will teach you fundamental microbiology techniques and the importance of genetic engineering tools in research!

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Before Starting:

  • Both strains of yeast and bacteria are genetically engineered to be selective and fluorescent.
  • The selectivity is important because:
    • It helps prevent contamination by ensuring only organisms with the correct plasmid (antibiotic resistance plasmid) can grow.
    • It maintains selective pressure on the organism to keep its plasmid. If the plasmid is lost, the organism may die, ensuring consistent results.

E. coli

Yeast

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The Streak-it Kit Co-Culture

At this stage of the experiment, you’ll start your culture from either a stab or a solid culture. If you choose to work with a solid culture, make sure to save your best culture plates for future use! These plates can be stored in the incubator or placed in a clean plastic bag in the fridge to preserve them.

How to Select the Best Colony:

  • Isolated: Choose a colony that is clearly separated from other growth on the plate.
  • Correct Phenotype: Ensure the colony matches the characteristics you identified earlier (e.g., size, shape, color, etc.).
  • Size: Opt for a larger colony to better observe its morphology and to have more cells available for streaking on the agar surface.

Selecting the right colony is key to ensuring the success of your co-culture experiment!

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Glossary

  • Autoinducers: Chemical signals produced by microorganisms that diffuse across membranes to enable detection and response within a cell colony.
  • Antibiotic: A compound that inhibits the growth or kills microorganisms, targeting either prokaryotic and/or eukaryotic cells.
  • Colony: A group of microorganisms growing on a substrate or medium.
  • Chloramphenicol: A type of antibiotic.
  • Extracellular: Refers to something located or occurring outside a cell or cells.
  • Gram-Positive Bacteria: Bacteria with thick layers of peptidoglycan surrounding their cell wall, but lacking an outer membrane.
  • Gram-Negative Bacteria: Bacteria with a thin peptidoglycan cell wall surrounded by an outer membrane containing polysaccharides and a capsule.
  • G418: A type of antibiotic.
  • Intracellular: Refers to something located or occurring inside a cell or cells.
  • Log-Phase/Exponential Phase: The phase of cell growth where cells actively divide, leading to an exponential increase in cell density. Cells are most viable during this phase.
  • Lawn: A dense collection of cells that must be diluted to create distinguishable colonies.
  • Parent Cell: The original cell that reproduces to form two daughter cells, continuing the cycle of reproduction.
  • Passive Diffusion: Movement of molecules from an area of higher concentration to lower concentration through a membrane, without requiring energy.
  • Quorum Sensing: A process where colonies communicate to regulate gene expression and control cell population density.
  • Threshold: The minimum level of a chemical required to produce an observable effect. Below this level, no effect is seen.