Molecular Cell Biology WS2011
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1 Molecular Cell Biology WS2011 Lecturer: Dr. Andreas Prokesch, Inst. for Genomics and Bioinformatics, TUG Purpose of this series of lectures: to offer you the basic knowledge required to know and understand the basics of molecular biology Form: lectures where the basics (+ supportive examples) will be covered orally, with visual support. Lectures are not mandatory... The examn pensum is covered in Molecular Cell Biology 6 ed, Author: Harvey Lodish, Publisher: W. H. Freeman and Company, New York. Additionally: (webpage supplementary to the text book) Molecular Biology, Author: David P. Clark, Publisher: Spektrum Akademischer Verlag. (helpful for explaining the scientific terms in german)
2 Molecular Biology: The Science of the Origins of Life, its Maintenance, and Reneval Monarch Danaus Plexippus North America
3 Mol Cell Biol - contents Fundamental basics (Basic knowledge) The Dynamic Cell basic introduction Chemical foundations (basic chemistry/energetics) Protein structure and function (basic structures, protein synthesis (translation+folding), analysis of protein) Nucleic Acids, the Genetic Code, and the Synthesis of Macromolecules (basic structures, mrna synthesis (transcription), analysis of nucleic acids and genomes) DNA Replication, Repair, and Recombination Functional concepts (Understanding basic Mol Biol) Recombinant DNA and Genomics (+manipulation of viruses and cells in culture) Genetic Analysis in Cell Biology (focus on biotechnological techniques for investigating genes) Molecular Structure of Genes and Genomes (packaging, functional modifications, etc.) Control of gene expression (transcriptional/post-transcriptional control) Biomembranes and the Subcellular Organization of Eukaryotic Cells (basic structures, function and structure of major organelles + visualization techniques) Transport across Cell Membranes (basic classes of transport mechanisms and their function) Cellular Energetics (Glycolysis, Aerobic Oxidation, and Photosynthesis) Cell-to-Cell Signaling: Hormones and Receptors (basics of how gene expression is regulated by external signals)
4 Chapter 1 The Dynamic Cell An overview
5 The Definition of Life Living things are able to... grow reproduce self-replicate generate and utilize energy process information evolve Bacteria Yeast Higher primates
6 Development of Life on Earth First record of Homo Sexual Reproduction & Multicellular organisms First Eucaryotes Simple Procaryotes Lipid bubbles+dna/rna => primitive cells First occurrence of selfreplicating organisms (life!) RNA? Lipid-bubbles? 13.7 ± 0.13 billion years
7 Book recommendation: Hoimar von Ditfurth: Im Anfang war der Wasserstoff Bill Bryson: Eine kurze Geschichte von fast allem
8 How is life organized?
9 Molecular Biology Gene: (ethymology) ancient greek: genos = birth Old Roman meaning of the word genius (Genie): a spirit representing the inborn power of individuals Current Biology: It is becoming increasingly apparent that interactions go in both directions. The 3 core diciplines are becoming overlapping
10 Mol Biol history Key Discoveries: 1928 Heritable changes can be transmitted from bacterium to bacterium through a chemical extract (the transforming factor) taken from other bacteria The transforming factor appears to be DNA The tetranucleotide hypothesis of DNA structure is overthrown (triplet code discovered) The structure of DNA is established to be a double helix (Nobel Prize 1962) The first complete draft of the nucleotide sequence of a copy of the human genome is completed (human genome project, HGS) Recent Epigenetics, variations in reversible chemical modifications of the human genome structure, is being recognized as equally important as the DNA nucleotide sequence in determining heritance
11 The Human Genome Project A complete draft of the nucleotide sequence of one copy of a human genome Lander et al., Nature 409: x 10 9 nucleotides in the human genome Average gene ~ 10 kb Venter et al., Science 291: , 2001 Book recommendation: Kevin Davies: Die Sequenz: Der Wettlauf um das menschliche Genom J. Craig Venter: Entschlüsselt: Mein Genom, mein Leben Number of genes now estimated at (~ 10% of the genome) Global colaboration: 2,500 scientists, 20 institutions But how to read these instructions...?
12 The molecules of life The activities of cellular molecules are governed by the basic principles of chemistry Cellular water, inorganic ions, and small organic molecules account for 75-80% of the living weight of a cell Macromolecules (DNA, RNA, proteins, polysaccharides, triglycerides, phospholipids) account for the remainder
13 Examples of cellular macromolecules
14 The plasma membrane separates the cell from the environment The fundamental structure of all cell membranes is the lipid bilayer Various membrane proteins present in the different cell membranes give each membrane a specific function
15 Cells are packed with molecules of various sizes
16 Phylogenetic tree of life Prokaryotes
17 Prokaryotic cells Single cell organisms Two main types: bacteria and archaea Relatively simple structure (just plasma membrane, no organelles)
18 Eukaryotic cells Single cell or multicellular organisms Plants, animals, and fungi Structurally more complex: organelles, cytoskeleton
19 Eukaryotic DNA is packaged into chromosomes Each chromosome is a single linear DNA molecule associated with proteins The total DNA in the chromosomes of an organism is its genome Humans: 23 chromosomes (22 autosomes and 1 sex chromosome) Dipolid
20 Basic genetic concepts illustrate the power of genes Gene Genetics (the study of (whole) individual genes) Genome Genomics (the study of genes in the context of all genes) Phenotype apparent difference Genotype genetic difference (not always apparent) Diploid (somatic cells), Haploid (gametocytes), aploid (mature red blood cells) Alleles (Dominant/Recessive/Codominant) mutant R + R -> Red Petunia, B+r -> Blue Petunia B+R -> Purple Petunia r+r -> White Petunia R+r B+B b+b R+b B+b Homozygous, heterozygous Mendelian Ratios (Gregor Mendel )
21 Classical Mendelian inheritance Passing on of alleles CC x cc: F1: c c C C Cc Cc Cc Cc F2: (Cc x Cc) C c C c CCCc Cc cc Homozygous Heterozygous Homozygous
22 The Central Dogma of MolBiol
23 Overview of four basic molecular genetic processes
24 Cells can reproduce to make identical clones Cell division occurs when one cell, after a period of growth, divides to become two daughter cells Most eukaryotic cells follow the cell cycle, an internal clock that determines the phases of cell growth and division Progress through the cell cycle is controlled at checkpoints Cells may leave the cell cycle and differentiate to perform specialized functions Cells may undergo programmed cell death as a way of balancing cell growth or generating structures during development (apoptosis)
25 Cells associate to form tissues Tissues are composed of cells and extracellular matrix Tissues may form organs Rudimentary tissues and an overall body plan form early in development due to a defined pattern of gene expression and the ability of cells to interact with other cells Many animals share the same basic pattern of development, which reflects commonalities in molecular and cellular mechanisms controlling development
26 Multiple tissues combine to create this artery
27 -or identical sheep Sharing identical genetic material (genomes)
28 At the completion of this lecture you should be able to: Name the basic contents of cells (water, salts, different macromolecules) Describe the basic concepts of genetics Explain Mendelian heritance State the central dogma of molecular biology
Molecular Biology: The Science of the Origins of Life, its Maintenance, and Reneval. -2.800 Mill. Adopted from http://www.chemistry.ucsc.
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Thymine = orange Adenine = dark green Guanine = purple Cytosine = yellow Uracil = brown
1 DNA Coloring - Transcription & Translation Transcription RNA, Ribonucleic Acid is very similar to DNA. RNA normally exists as a single strand (and not the double stranded double helix of DNA). It contains
The Origin of Life. The Origin of Life. Reconstructing the history of life: What features define living systems?
The Origin of Life I. Introduction: What is life? II. The Primitive Earth III. Evidence of Life s Beginning on Earth A. Fossil Record: a point in time B. Requirements for Chemical and Cellular Evolution: