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بخش مهندسی بیوتکنولوژی عنوان درس: زیست شناسی سلولی و مولکولی ( Cellular and Molecular )Biology تعداد واحد( 2 :نظری) روش ارزیابی: %15سمینار %35 ،میان ترم و %50پایان ترم Scientific Journals • Cell • Science • Nature • Nature Reviews Molecular Cell Biology • Nature Reviews Genetics • Annual Review of Genetics سر فصل مطالب • تعریف بیولوژی ،مشخصات سلولی ،بیولوژی سلولی و شاخه های آن ،ویژگیهای موجودات مدل در مطالعات سلولی ،پروتئین ها به عنوان مولکولهای فعال سلولی ،قابلیت دسترسی بیولوژیکی به پروتئین ها ،اندامک های دخیل در سنتز ،تاخوردگی ،تغیر و تخریب پروتئین ها .نقش گلیکوزیالسیون در سلول ،برهمکنش پروتئین و قند ،غشاهای سلولی و بررسی اجزای آن ،انواع پروتئین های غشایی ،تنظیم فعالیت های سلولی به کمک سیگنال های غشا و اجزای آن ،برهمکنش پروتئین چربی و قند در سلول، ساختار سلول گیاهی و اندامک ها ،غشای سلولی و انتقال منابع • Bruce, Alberts, et al. Essential cell biology. Garland Science. • Gerald, Karp. Cell and Molecular Biology: Concepts and Experiments. John Wiley & Sons. • Harvey, Lodish, et al. Molecular cell biology. The origins of the universe • Cosmologists believe that the universe was born 14 billion years ago in the Big Bang Origin-of-life conundrum • The crash of meteors on early Earth likely generated hydrogen cyanide, which could have kick-started the production of biomolecules needed to make the first cells. Chicken-and-egg problem! • Central dogma • Alkaline formose reaction • Miller-Urey spark discharge experiment • Oro’s experiments The origin of life probably occurred in three overlapping phases The RNA world hypothesis • Store information • Self replicate • Self-cleavage • Cleavage of other RNAs (RNase P) • Catalyze reactions (ribozymes) RNA Or PNA Or TNA Evolution of life First evidence for eukaryotic cells— structures resembling single-celled algae—about 1.4 billion years ago and for multicellular algae about 0.9 billion years ago. Aspects of biological science • Astrobiology • Biochemistry • Botany • Biophysics • Cell biology • Computational biology • Ecology • Evolutionary biology • Genetics • Marine biology • Microbiology • Molecular biology • Paleobiology • Physiology • Structural biology • Systems biology • Synthetic biology • Zoology بیوسفر اکوسیستم موجودات زنده اندام بافت سلول اندامک ها مولکول The Two Empires and Three Domains of Life What Defines a Cell? What Other Components Do Cells Have? Figure 2: The composition of a bacterial cell Most of a cell is water (70%). The remaining 30% contains varying proportions of structural and functional molecules How Did Cells Originate? Figure 5: The origin of mitochondria and chloroplasts Mitochondria and chloroplasts likely evolved from engulfed prokaryotes that once lived as independent organisms. At some point, a eukaryotic cell engulfed an aerobic prokaryote, which then formed an endosymbiotic relationship with the host eukaryote, gradually developing into a mitochondrion. Eukaryotic cells containing mitochondria then engulfed photosynthetic prokaryotes, which evolved to become specialized chloroplast organelles. Two competing evolutionary scenarios for the origin of eukaryotic cells and their mitochondria. (A) The traditional view posits that the bulk of eukaryotic cellular complexity arose in a stepwise fashion prior to the endosymbiotic uptake (by phagocytosis) of the a-proteobacterium that became the mitochondrion. (B) The hydrogen hypothesis invokes a metabolic symbiosis between methane-producing archaea and a-proteobacteria. In this scenario eukaryotic cellular complexity arises after endosymbiosis. Both models involve extensive gene transfer from the a-proteobacterium to the archaeal host and the evolution of a system for targeting nucleus encoded proteins to the endosymbiont-turned organelle. Earth’s biogeologic clock Model organisms • All cells are thought to be descended from a common ancestor, whose fundamental properties have been conserved through evolution. Thus, knowledge gained from the study of one organism contributes to our understanding of others, including ourselves. • Short generation time • Characterized genome • Similarity to humans • Extensively studied in research laboratories • Small, easy and cheap to maintain and manipulate • Fewer ethical concerns Current models • Viruses Phage lambda SV40 Tobacco mosaic virus Herpes simplex virus • Prokaryotes • Escherichia coli • Bacillus subtilis Current models • Eukaryotes Caenorhabditis elegans Drosophila melanogaster Mus musculus Xenopus Zebrafish HeLa cell Current models • Eukaryotes Chlamydomonas reinhardtii Neurospora crassa Saccharomyces cerevisiae Arabidopsis thaliana Brachypodium distachyon Tobacco BY-2 cells Rice Populus جلسه دوم proteins • Proteins are biomacromolecules present in all organisms and they have a large variety of functions. • Proteins are linear chains of L-α-amino acids . • Structural: offering stiffness and rigidity to fluid biological components. Collagen is the most abundant structural protein in mammals or Scafold proteins. • Catalysis of chemical reactions as enzymes. Only a small region of an enzyme called the active site binds the substrate and contains the catalytic residues. • Receptors: they usually have a ligand-binding site on the cell surface and an effector domain within the cell, which may have enzymatic activity or may undergo a conformational change. • Signaling proteins: • Channels for molecules to pass through the cell membrane, for example the potassium channel. • Transport: Those proteins bind small molecules and transport them to other locations in the cell or organism. For example haemoglobin transports oxygen. • Motor proteins: responsible for moving other proteins, organelles, cells even whole organisms. Molecular machine • most functions in the cell are not carried out by single protein enzymes, but by macromolecular complexes containing multiple subunits with specific functions. • Many of these complexes are described as “molecular machines.” Replisome, Spliceosome, and ribosome Proteome • A proteome is the entire set of proteins expressed by a genome, cell, tissue, or organism at a certain time. • Structural proteomics • Expressional or Analytical Proteomics • Functional or Interaction Proteomics Hierarchical Structure of Proteins • A key concept in understanding how proteins work is that function is derived from three-dimensional structure, and three dimensional structure is determined by both a protein's amino acid sequence and intramolecular noncovalent interactions. Hierarchical Structure of Proteins • The Primary Structure of a Protein Is Its linear Arrangement of Amino Acids -Aia-Giu-Val-Thr-Asp-Pro-Giy- Hierarchical Structure of Proteins • Secondary Structures Are the Core Elements of Protein Architecture • alpha Helix • Beta Sheet • Beta Turn • irregular structure • Random coil alpha Helix • در مارپیچ آلفا اسکلت مولکول به شکل مترپیچ می باشد که در آن اتم اکسیژن کربونیل از هر پیوند پپتیدی با اتم هیدروژن آمید 4اسید آمینه جلوتر پیوند هیدروژنی تشکیل می دهد. Coiled coil Beta Sheet Beta turn • از 4اسید آمینه تشکیل شده اند. • تا خوردن پلی پپتیدهای بلند را تسهیل میکنند • گلیسین و پرولین رایج ترین اسیدهای آمینه در این ساختار می باشند. Tertiary Structure Is the Overall Folding of a Polypeptide Chain • Tertiary structure refers to the overall conformation of a polypeptide chain-that is, the three-dimensional arrangement of all its amino acid residues. Quaternary Structure • Many proteins are made up of multiple polypeptide chains, often referred to as protein subunits. • The quaternary structure refers to how these protein subunits interact with each other and arrange themselves to form a larger aggregate protein complex. • hydrogen-bonding, disulfide-bridges and salt bridges affect stability of protein complex. • Proteins usually fall into one of three broad structural categories, based on their tertiary structure • Globular proteins • Fibrous proteins • Integral membrane proteins Structural Motifs • A particular combination of two or more secondary structures that form a distinct three-dimensional structure. Domain • Distinct regions of protein structure often are referred to as domains. • Functional • Structural • Topological Protein Folding • In thermodynamic terms, the native state is usually the conformation with the lowest free energy (G) • What features of proteins limit their folding from very many potential conformations to just one? Folding of Proteins in Vivo • Molecular chaperones: HSP70, Bip,Dnak • Chaperonins: GroEL/GroES,TriC Protein function • The molecule to which a protein binds is called its ligand. • Specificity • Affinty • Molecular complementarity Regulating Protein Function • Increase or decrease the steady-state level of the protein • Change the intrinsic activity • Change in location or concentration with in the cell of the protein itself, the target of the protein's activity (e.g., an enzyme's substrate), or some other molecule required for the protein's activity (e.g., an enzyme's cofactor). Regulated Synthesis and Degradation of Proteins • The life span of intracellular proteins varies from as short as a few minutes to as long as the age of an organism. • One major pathway is degradation by enzymes within lysosomes (autophagy) Proteasome • Proteasomes are very large, protein-degrading macromolecular machines