BME 42-620 Engineering Molecular Cell Biology. Lecture 02: Structural and Functional Organization of



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BME 42-620 Engineering Molecular Cell Biology Lecture 02: Structural and Functional Organization of Eukaryotic Cells BME42-620 Lecture 02, September 01, 2011 1

Outline A brief review of the previous lecture Prokaryotic versus eukaryotic cells Sources of cells for experimental studies Structural and functional organization of eukaryotic cells Overview of model organisms 2

Outline A brief review of the previous lecture Prokaryotic versus eukaryotic cells Sources of cells for experimental studies Structural and functional organization of eukaryotic cells Overview of model organisms 3

Some Universal Properties of Cells Cells proliferate through division. Hereditary information is transferred between generations in cell division. Proteins are synthesized through regulated gene expression. Cells are structurally and functionally organized. Cells actively interact with their environment. Cells can process information using their signaling networks. 4

Outline A brief review of the previous lecture Prokaryotic versus eukaryotic cells Sources of cells for experimental studies Structural and functional organization of eukaryotic cells Overview of model organisms 5

Prokaryotic vs Eukaryotic Cells (I) Cells can be classified into two families - Prokaryotic cells do not have a distinct nucleus. - Eukaryotic cells have a distinct nucleus. - Eukaryotic cells are structurally and functionally more advanced than prokaryotic cells. Organisms can be classified into - Prokaryotes are organisms made of a prokaryotic cell. - Eukaryotes are organisms made of a single or multiple eukaryotic cells. Prokaryotic cell (bacteria Vibrio cholerae) Eukaryotic cell 6

Prokaryotic vs Eukaryotic Cells (II) Eukaryotes can be further classified into two families - Protozoa: single-cell eukaryotes - Metazoa: multiple-cell eukaryotes Some advanced features lacking in prokaryotic cells - Membranous organelles. - Cytoskeletal system and associated proteins. - The ability to form a mitotic spindles for division. -Two copies of genes in eukaryotic cells (diploid). One copy of genes in prokaryotic cells (haploid). - Three RNA synthesis enzymes. There are almost always exceptions in biology. 7

Prokaryotic vs Eukaryotic Cells (III) Karp, Cell and Mol. Biol., Wiley, 5e, 2008 8

Classification of Prokaryotic Cells (I) Two main branches of prokaryotic cells - Archaea - Bacteria Different shapes & sizes of bacteria E. coli Only a small fraction (~1%) of prokaryotes have been identified. 9

Classification of Prokaryotic Cells (II) Bacteria and archaea are differentiated based on their genetic information. Difference between bacteria and archaea - Archaea is closer to eukaryotes in how genetic information is handled, i.e. replication, transcription, translation. - Bacteria is closer to eukaryotes in metabolism and energy conversion. Examples of bacteria - Mycoplasma: smallest cell; 0.2 μm in diameter, no cell wall. - Cyanobacteria: capable of photosynthesis and nitrogen fixation; survive almost everywhere. - E. coli: a convenient protein synthesis machine; important for biotechnology and microbiology. 10

Classification of Prokaryotic Cells (III) Examples of archaea - Some archaea can live under extreme conditions - Halophiles: live in extremely salty environments - Acidophiles: live under ph as low as 0 - Thermophiles: live under very high temperature Most bacteria and archaea have 1000-6000 genes. - Reproduce very fast and effectively Prokaryotes have many useful applications. - Biology, biotechnology - Environment protection - Energy production 11

Evolution of Cells: the Tree of Life Alberts MBoC 5e Three major domains of living organisms: bacteria, archaea, eukaryotes. - Formation of our planet: ~4.5 billion years ago -Emergence of common ancestor: ~3.5 billion years ago - Emergence of single-cell eukaryotes: ~2 billion years ago - Emergence of multiple-cell eukaryotes: ~ 1 billion years ago The phylogenetic/evolutionary tree is constructed based on comparison of nucleotide or amino acid sequences of organisms, specifically the following sources. - nuclear DNA, RNA; amino acid sequences - mitochondria RNA - ribosome RNA 12

Computational Molecular Biology (Bioinformatics) A (adenine); G (guanine); C (cytosine); T (thymine) Source: ribosomal RNA Methanococcus: an archaea Computational tools are required to analyze sequences of DNA, RNA, or proteins. 13

Classification of Eukaryotic Cells Protist: unicellular eukaryotes Fungi Plant cells Animal cells - Examples: amoeba; algae - Examples: yeast; mold; mushroom Budding yeast cells 14

Genomes of Prokaryotes vs Eukaryotes 15

A Bacterial Cell with a Synthetic Genome D. G. Gibson et al, Science, 329, 52 (2010). 16

Outline A brief review of the previous lecture Prokaryotic versus eukaryotic cells Sources of cells for experimental studies Structural and functional organization of eukaryotic cells Overview of model organisms 17

Sources of Cells for Experimental Studies Two main sources of cells: primary cells & cell lines. - Additional source: differentiated stem cells Primary cells are directly derived from a living organism. Primary cells undergo a limited, predetermined number of cell divisions before arresting permanently in a process called senescence. Primary mouse hippocampal neuron 18

Cell Senescence (Aging) telomeres 19

Cultured Cell Lines A cell line is a permanently established cell culture that can proliferate indefinitely given suitable media and environment. Cultured cells permit studies of individual id cells under experimentally controlled conditions. Many cell lines are derived from cancer cells. 20

An Example: HeLa Cells HeLa cells are derived from cervical cancer cells taken without permission from Henrietta Lacks, who died on October 4, 1951. First cultured by George Otto Gey. Commonly used as a human cell line for research. 21

Several Commonly Used Terms Epithelial cells: cells that form sheets (epithelia) to cover the outer surface of a structure or lining of a cavity. Endothelial cells: flattened cells that form the lining (endothelia) of blood and lymphatic vessels. Fibroblasts: cells that are commonly found in connected tissues and form the extracellular matrix. Further information: - http://www.atcc.org - R. I. Freshney, Culture of animal cells, Wiley-Blackwell, 6/e, 2010. 22

Outline A brief review of the previous lecture Prokaryotic versus eukaryotic cells Sources of cells for experimental studies Structural and functional organization of eukaryotic cells Overview of model organisms 23

Organization of Eukaryotic Cells A simplified engineering view of structural and functional organization of cells. - Material: production, recycling, sorting/packaging/transport/delivery - Structure: assembly, disassembly - Energy: production, distribution - Information: collection, processing - Motion: generation, control 24

Structural Organization of Eukaryotic Cells Some examples - Structure: cytoskeleton - Structure: plasma membrane - Material production: ribosome - Material sorting: ER and Golgi - Material degradation: lysosome - Material transport: cytoskeleton, motors - Material import: endosome - Energy: mitochondria and peroxisome - Information: receptors, protein messengers, second messengers - Information/structure: nucleus Individual units often have multiple functions. 25

Structure Scaffold: Cytoskeleton Cytoskeleton filaments -Actin - Microtubule - Intermediate filament Centrioles and centrosomes (MTOC) - initiation of microtubule growth - microtubule organization 26

Primary function: protein synthesis Material Production: Ribosome Location: free in cytoplasm or bound to endoplasmic reticulum Multiple ribosomes can form polysomes 27

Material Packaging, Sorting and Shipping: ER & Golgi (I) Rough ER & Smooth ER Rough ER Function - Protein processing and quality control - ER membrane is the site for membrane protein synthesis - Coordinate with Golgi for protein sorting Smooth ER function - Required for several metabolic processes 28

Material Packaging, Sorting and Shipping: ER & Golgi (II) Modifying, sorting, and labeling synthesized proteins from ER - Golgi is often thought as the postal office for the cell Packaging proteins into vesicles and sort vesicles for transportation 29

Material Transport System: Cytoskeleton and Motility Apparatus Cytoskeleton filaments -Actin - Microtubule Molecular motors - Myosin - Kinesin - Dynein 30

Material Degradation and Recycling: Lysosome Lysosome: digest macromolecules, including those from phagocytosis, endocytosis, autophagy Contains - Proteases that digest protein - Nucleases that digest nucleic acids - Carbohydrase that digest carbohydrates - Lipase that digest lipids 31

Energy Generation/Distribution: Mitochondria (I) Generation and distribution of ATP Regulation of many other metabolic processes, including aging 32

Energy Generation/Distribution: Mitochondria (II) 33

Energy Generation/Distribution: Peroxisome Found in all eukaryotic cells. Prokaryotes lack peroxisome. Peroxisome participates in the oxidation of fatty acid, amino acid, and other metabolites 34

Structure: Plasma Membrane A fragile separation of cells from their environment; ~5nm in thickness Diffusion of lipids and membrane proteins Restricted exchange across the membrane - pumps - carriers -chambers 35

Receptors Information: Collection & Processing Protein messengers Second messengers 36

Information Storage and Transcription: Nucleus Provides enclosure to chromosome and genetic information Transcription of DNA into mrna Assembly of ribosome in nucleolus Control material import and export through nuclear pores. 37

Scale of Cells Live imaging: light microscope Below 100nm, electron microscopy Below 1 nm: crystallography, NMR, spectroscopy 38

MBoC 5/e chapter 1 Required ed Reading 39

Questions? 40