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Lecture 1 Introduction Goals of the Course and today’s Biological Research

Lecture 1 Introduction Goals of the Course and today’s Biological Research The length and time scales of biological processes Cell as an elementary unit of life The unifying molecular paradigm Prokaryotes and Eukaryotes The tree of life Cells are open system operating far from equilibrium

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Lecture 1 Introduction Goals of the Course and today’s Biological Research

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  1. Lecture 1 Introduction Goals of the Course and today’s Biological Research The length and time scales of biological processes Cell as an elementary unit of life The unifying molecular paradigm Prokaryotes and Eukaryotes The tree of life Cells are open system operating far from equilibrium Physics laws hold everywhere

  2. BSCI 338O/BIOL 708O Cell Biology from a Biophysical Perspective Instructor: Sergei Sukharev sukharev@umd.edu 301-405-6923 Lectures: Tue, Thu 3:30-4:45 pm, PLS 1180 Web http://chemlife.umd.edu/classroom/bsci338-biol708/syllabus.html

  3. Main Text: Molecular Cell Biology by Lodish et al. (6th or 5th Edition) Freeman & Co., 2007 or 2004 Other helpful reading: Physical Biology of the Cell by Rob Phillips, Jane Kondev and Julie Theriot. Garland Science 2008 Biological Physics. Energy, Information, Life by Philip Nelson Freeman & Co., 2004 Molecular and Cellular Biophysics by Meyer Jackson Cambridge University Press, 2006 Mechanics of Motor proteins and Cytoskeleton by Jonathan Howard Sinauer, 2001 Cell Physiology Sourcebook. A Molecular Approach (3d Edition) Edited by Nicholas Sperelakis. Academic Press, 2001

  4. The purpose of the course: A concise review of major concepts describing cellular function with the focus on unifying principles and mechanisms, with links to the physico-chemical properties of the components; a consideration of the energetic and kinetic aspects of the processes; and the strategies and key techniques used in performing the studies. The course will help students identify interesting mechanistic biological problems that they can pursue in new ways utilizing their unique background. (not the best way to fix the GPA for struggling pre-meds) Open-book exams: Two mid-term exam (30+30% of the total points) The final scheduled for Wed, May 20, 10:30-12:30, (40% of the grade)

  5. What is today’s Biology? Primary observation Accumulation and sorting of phenomenology Identification of molecular players and compartments Putting events in causative sequences Finding and comparing homologous processes/components in other organisms Separating the essential (minimal) and auxiliary components Solving structures Interpreting structures, predicting transition pathways and mechanisms In the end, THE BEST BIOLOGICAL RESEARCH is a pursuit of THE PHYSICO-CHEMICAL NATURE of a BIOLOGICAL PHENOMENON

  6. Length scale Human body ~2 m Organ, tissue ~10-1 m Cell ~10-4 - 10-5 m Subcellular organelle ~ 10-5 -10-7 m Macromolecule 10-8 – 10-9 m Small molecule (solvent) 2.8·10-10 m

  7. Macromolecular Scales From P. Nelson

  8. Time scales Population, species lifespan 102-108 yr Organismal lifespan 1-103 yr Cell cycle/genome duplication 20 min – 48 hr Transcription rate 10-20 nucleotides/s Transport reaction rates 102 -108 s-1 Protein domain movements 10-8 – 10-1 s Free sidechain correlation times 10-11-10-6 s Solvent correlation times 10-10-10-11s Retinal photoisomerization 2·10-13 s Covalent bond vibration 6·1012 - 1014 s-1

  9. The Tree of Life (Medical School version)

  10. Eubacteria

  11. Archaea

  12. Ciliate: Pramecium

  13. Dictyostelium discoideum

  14. Colonies of alga

  15. Blood cells

  16. Neuron

  17. Intestinal epithelium

  18. Wood

  19. The CENTRAL DOGMA

  20. DNA: Legislative Branch

  21. Proteins: Executive Branch

  22. Genome (Genomics: data mining, sequence assignment) Transcription regulation, alternative splicing, Transcripts (RT PCR, micro-array analysis) Translation Proteome (Mass-spectrometry, Proteomics) Folding, sorting, post-transcriptional modification, targeting, complex assembly, co-factors, activation, Functional traits (Phenotype, function, physiology, biochemistry, biophysics)

  23. 1927 1990’s

  24. C6H12O6 + 6O2 6 CO2 +6H2O 686 kcal/mol 30 ADP + 30 Pi 30 ATP +30 H+ + 30 H20 219 kcal/mol ATP = ADP+Pi 32% efficiency 7.3 kcal/mole

  25. Cells are open systems operating far from equilibrium However many of the “local and fast” events can be treated as equilibrium processes Keq Complete equilibrium = death

  26. + + Principles of Physics hold everywhere (and set their limitations) + voltage-gated channel o c electrometer Voltage dependence of open probability Charged transmembrane helix = voltage sensor

  27. unmyelinated fiber myelinated fiber =regular wire =High-frequency cable

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