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Майнор по биоинформатике

Мария Попцова

Лекция 1

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Правила игры

Окончательная оценка = Округление

(0.3*((ДЗ1 + ДЗ2 + ДЗ3 + ДЗ4)/4)+

0.3* ((Qz1+Qz2+Qz3+Qz4+Qz5+Qz6+Qz7+Qz8+Qz9+Qz10)/10)+

0.4*Экз)

Экз – конец 2 модуля (письменный)

1 модуль – 2 ДЗ и 5 квизов

2 модуль – 2 ДЗ и 5 квизов

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Клетка-город

Объект биологии

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Объекты в биологии

Биологический объект - это живой организм

Все живые тела состоят из клеток

Клетка – элементарная единица живого

Все клетки имеют одинаковые принципы организации

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Клетка как город

Внешняя стена с воротами => мембрана с каналами
Кремль => ядро
Библиотека => геном
Библиотека находится в Кремле => геном находится в ядре
Роботы => белки
В книгах библиотеки (геноме) содержатся инструкции как делать роботов (белки)

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ЧТО ТАКОЕ ГЕНОМ?

Для биолога

Для биоинформатика

Ряд Нобелевских премий 1950-1970

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Геномы разных органзимов

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Вторичная структура – альфа-спираль и бета-лист

Альфа-субъединица АТФ-синтетазы

Лайнус Полинг

Нобелевская премия по химии 1954

Обитатели клетки-города

The best X-ray pictures of proteins in the 1930s had been made by the British crystallographer William Astbury

Pauling had formulated a model for the structure of hemoglobin in which atoms were arranged in a helical pattern, and applied this idea to proteins in general.

In 1951, based on the structures of amino acidsIn 1951, based on the structures of amino acids and peptidesIn 1951, based on the structures of amino acids and peptides and the planar nature of the peptide bond, Pauling, Robert CoreyIn 1951, based on the structures of amino acids and peptides and the planar nature of the peptide bond, Pauling, Robert Corey and Herman BransonIn 1951, based on the structures of amino acids and peptides and the planar nature of the peptide bond, Pauling, Robert Corey and Herman Branson correctly proposed the alpha helixIn 1951, based on the structures of amino acids and peptides and the planar nature of the peptide bond, Pauling, Robert Corey and Herman Branson correctly proposed the alpha helix and beta sheetIn 1951, based on the structures of amino acids and peptides and the planar nature of the peptide bond, Pauling, Robert Corey and Herman Branson correctly proposed the alpha helix and beta sheet as the primary structural motifs in protein secondary structure.^[73]^[73]^[74]

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Proteins are made of 20 amino acids

Over 100 amino acids exist in nature

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Белок - текст, написанный на алфавите

из 20 букв

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Genome is made of DNA

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DNA is made of 4 nucleotides

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Chargaff’s rules�

1^st Chargaff’s rule

А=Т and G=C in double-stranded DNA

2^nd Chargaff’s rule

А=Т и G=C in single-stranded DNA

http://www.youtube.com/watch?v=HvJlnujmYcg

Human Genome:

A=30.9% and T=29.4%; G=19.9% and C=19.8%

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Good Quality DNA X-Ray images

Морис Уилкинс и Розалинд Франклин
.

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Nobel Prize in 1962

Геном - текст, написанный на алфавите

из 4 букв

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Расшифровать генетический код

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Георгий Гамов

- объясняет загадочное число 20.

- число различных ромбовых комбинаций именно в такой модели равно как раз двадцати.

Бубновый код

Треугольный (комбинаторный)

Перекрывающиеся

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Клуб РНК-галстуков

«Мы просто пили калифорнийское вино, и нам приходили идеи» Георгий Антонович Гамов

Джордж Гамов, физик, ALA — аланин�Ричард Фейнман, физик, GLY- глицин�Джеймс Уотсон, биолог, PRO — пролин�Макс Дельбрюк, физик, TRP триптофан�Фрэнсис Крик, биолог, TYR – тиразин

Эрвин Чаргаф, биохимик, LYS – лизин

Francis Crick, Alexander Rich, George Gamow, James Watson, Melvin Calvin

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Код без запятых

Синтез белков происходит не на ДНК, а на посреднике в виде молекулы РНК

Гипотеза Крика об адаптерных молекулах

Проблема рамки считывания и значащих и незначащих кодонов

Френсис Крик

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1957, Francis Crick �a talk at University College, London

Francis Crick’s unpublished 1956 sketch of the central dogma. (Image: Wellcome Library, London.)

стала известна

как Crick’s Central Dogma

или

Центральная догма молекулярной эволюции

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Открытие РНК

Об РНК знали с 1868 года, когда Фридрих Мишер открыл нуклеиновые кислоты.

1961 - Две публикации в Nature

announcing the isolation of messenger RNA (mRNA)

Theoretical Review François Jacob and Jacques Monod about role of mRNA in gene regulation

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V Международный биохимический конгресс

1961

Москва, 10-16 августа

Ниренберг М.В., Маттеи Г. // Тр. V Международ. биохим. конгресса. Симп.1. 1962.

С.211—226

Значит кодон UUU кодирует фенилаланин.

They produced RNAThey produced RNA composed solely of uracilThey produced RNA composed solely of uracil, a nucleotideThey produced RNA composed solely of uracil, a nucleotide that only occurs in RNA. They then added this synthetic poly-uracil RNA into a cell-free extract of Escherichia coli which contained the DNA which contained the DNA, RNA which contained the DNA, RNA, ribosomes which contained the DNA, RNA, ribosomes and other cellular machinery for protein which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine, the resulting protein was also radioactive which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine, the resulting protein was also radioactive. They realized that they had found the genetic code which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine, the resulting protein was also radioactive. They realized that they had found the genetic code for phenylalanine which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine, the resulting protein was also radioactive. They realized that they had found the genetic code for phenylalanine: UUU (three uracil which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine, the resulting protein was also radioactive. They realized that they had found the genetic code for phenylalanine: UUU (three uracil bases in a row) on RNA. This was the first step in deciphering the codons which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine, the resulting protein was also radioactive. They realized that they had found the genetic code for phenylalanine: UUU (three uracil bases in a row) on RNA. This was the first step in deciphering the codons of the genetic code and the first demonstration of messenger RNA (see Nirenberg and Matthaei experiment)

Исследователи послали в печать первую работу в марте 1961 г., а затем представили ее на одной из секций V Международного биохимического конгресса, который проходил в Москве 10—16 августа (Ниренберг М.В., Маттеи Г. // Тр. V Международ. биохим. конгресса. Симп.1. 1962. С.211—226).

Ниренберг М.В., Маттеи Г. // Тр. V Международ. биохим. конгресса. Симп.1. 1962. С.211—226

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Эксперимент Ниренберга

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1968 - Нобелевская премия �по физиологии и медицине

Ниренберг, Хорана,

Холли

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Центральная догма �молекулярной биологии�

ДНК

РНК

Белок

Репликация

Транскрипция

Трансляция

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Replication

https://www.youtube.com/watch?v=bee6PWUgPo8

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Transcription and Translation

https://www.youtube.com/watch?v=TfYf_rPWUdY

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The Nobel Prize in Chemistry 2006
Roger D. Kornberg ”for his studies of the molecular basis of eukaryotic transcription” –

” how the genetic information is copied from DNA into what is called messenger-RNA”

The Nobel Prize in Physiology or Medicine 1959
Severo Ochoa and Arthur Kornberg “for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid”
“how genetic information is transferred from one DNA-molecule to another. ”

REPLICATION

TRANSCRIPTION

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Ribosome

The Nobel Prize in Chemistry 2009
Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath “for studies of the structure and function of the ribosome”

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Transcription factors

The Nobel Prize in Physiology or Medicine 1965
François Jacob, André Lwoff and Jacques Monod “for their discoveries concerning genetic control of enzyme and virus synthesis”

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Transcription factors

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Membrane

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Mitochondria –Монетный двор

Paul D. Boyer and John E. Walker "for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)" and the other half to Jens C. Skou "for the first discovery of an ion-transporting enzyme, Na+, K+ -ATPase."

The Nobel Prize in Chemistry 1997

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Cell Transport

Nobel Prize in Medicine Awarded for Cell Transport Discoveries 2013

James E. Rothman, Randy W. Schekman and Thomas C. Südhof “for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells”

The Nobel Prize in Physiology or Medicine 1999

Günter Blobel “for the discovery that proteins have intrinsic signals that govern their transport and localization in the cell”

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Уборка мусора

The Nobel Prize in Physiology or Medicine 2016

Yoshinori Ohsumi “for his discoveries of mechanisms for autophagy”

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https://www.youtube.com/watch?v=fpHaxzroYxg