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:http://whfreeman.com/lodish6e (webpage supplementary to the text book)

“Molecular Biology”, Author: David P. Clark, Publisher: Spektrum Akademischer Verlag.(helpful for explaining the scientific terms in german)

Molecular Biology:The Science of the Origins of Life, its Maintenance, and Reneval

MonarchDanaus Plexippus

North America

Mol Cell Biol - contentsFundamental 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)

Chapter 1

The Dynamic CellAn overview

The Definition of Life

Living things are able to...growreproduceself-replicategenerate and utilize energyprocess informationevolve

Bacteria Yeast Higher primates

Development of Life on Earth

First occurrence of self-replicating organisms (life!)

RNA? Lipid-bubbles?

Lipid bubbles+DNA/RNA => primitive cells

Simple Procaryotes

First Eucaryotes

Sexual Reproduction & Multicellular organisms

First record of Homo

13.7 ± 0.13 billion years

Book recommendation:Hoimar von Ditfurth: Im Anfang war der Wasserstoff

Bill Bryson: Eine kurze Geschichte von fast allem

How is life organized?

Current Biology: It is becoming increasingly apparent that interactions go in both directions. The 3 core diciplines are becoming overlapping

Molecular Biology

Gene: (ethymology)

ancient greek: “genos” = birth

Old Roman meaning of the word “genius” (Genie): a spirit representing the inborn power of individuals

Mol Biol history

Key Discoveries:1928 Heritable changes can be transmitted from

bacterium to bacterium through a chemicalextract (the transforming factor) takenfrom other bacteria.

1944 The transforming factor appears to be DNA.1950 The tetranucleotide hypothesis of DNA

structure is overthrown (triplet code discovered).1953 The structure of DNA is established to be a

double helix (Nobel Prize 1962).2003 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

The Human Genome ProjectA complete draft of the nucleotide sequence of one copy of a human genome

But how to read these instructions....?

3 x 109 nucleotides in the human genome

Average gene ~ 10 kb

Number of genes now estimated at 20 000 – 30 000 (~ 10% of the genome)

Global colaboration: 2,500 scientists, 20 institutions

Lander et al., Nature 409:860-921 2001

Venter et al., Science 291:1304-1351, 2001

Book recommendation:Kevin Davies: Die Sequenz: Der Wettlauf um das menschliche Genom

J. Craig Venter: Entschlüsselt: Mein Genom, mein Leben

The molecules of life

The activities of cellular molecules are governed by the basic principles of chemistryCellular water, inorganic ions, and small organic molecules account for 75-80% of the living weight of a cellMacromolecules (DNA, RNA, proteins, polysaccharides, triglycerides, phospholipids) account for the remainder

Examples of cellular macromolecules

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

Cells are packed with molecules of various sizes

Prokaryotes

Phylogenetic tree of life

Prokaryotic cellsSingle cell organismsTwo main types: bacteria and archaeaRelatively simple structure (just plasma membrane, no organelles)

Eukaryotic cells

Single cell or multicellular organismsPlants, animals, and fungiStructurally more complex: organelles, cytoskeleton

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

Eukaryotic DNA is packaged into chromosomes

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 differenceGenotype – 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 PetuniaR+r B+B b+bR+b B+b

Homozygous, heterozygousMendelian Ratios (Gregor Mendel 1823-1885)

Classical Mendelian inheritance

CC x cc:F1:

C Cc

c

Cc Cc

Cc Cc

F2:(Cc x Cc)

C cC

c

CCCc

Cc cc

Passing on of alleles

Homozygous Heterozygous Homozygous

The Central Dogma of MolBiol

Overview of four basic molecular genetic processes

Cells can reproduce to make identical “clones”

Cell division occurs when one cell, after a period of growth, divides to become two daughter cellsMost eukaryotic cells follow the cell cycle, an internal clock that determines the phases of cell growth and divisionProgress through the cell cycle is controlled at checkpointsCells may “leave” the cell cycle and differentiate to perform specialized functionsCells may undergo programmed cell death as a way of balancing cell growth or generating structures during development (apoptosis)

Cells associate to form tissues

Tissues are composed of cells and extracellular matrixTissues may form organsRudimentary 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 cellsMany animals share the same basic pattern of development, which reflects commonalities in molecular and cellular mechanisms controlling development

Multiple tissues combine to create this artery

-or identical sheepSharing identical genetic material (genomes)

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