APh161: Physical Biology of the CellWinter 2005When: TTh, 9-10:30 AM. We will have an aggressive set of makeup lecturesright from the start of the term since I will miss the first two classes and oneother class during the term.Who: You and me (Rob Phillips, x 3374, [email protected], 221Steele). The TAs for the course are Mandar Inamdar (help sessions), x3106,[email protected] 226 Steele, Hernan Garcia (grader), x3106, [email protected], 230 Steele, Rizal Hariadi (grader), x RP, [email protected] am always happy to see you, but with certainty, the best way to contactme is by email. After that, the best approach is to schedule a time to see methrough my secretary, Katie Miller (x6337, [email protected], 138 Broad).Where: 104 WatsonWhat: See below!How: Lecture twice a week and weekly homework. No exams. Your gradeswill be based upon your homework grades (75 %) as well as on an end ofterm poster during the class poster session. I will NOT accept ANY latehomeworks (late means anytime after class is over the day the homeworkis due) unless you have a mindblowingly good excuse. As for collaborationwith others, you may discuss the homework with others, but your explana-tions and derivations must be your own and your logic should be carefullyexplained and the significance of your results should also be explained. Ifyou hand us a sloppy homework the grader will likely be unable to penetrateyour logic and you will lose points.1Reading: I have ordered a number of outstanding books which are availableat the bookstore. I will certainly be assigning readings from all of them. Inaddition, the course webpage will have a repository of required reading fromthe original literature. However, the two most important texts for the courseare a) Essential Cell Biology by Alberts et al., and b) Physical Biologyof the Cell, an incomplete draft of a book that I am writing with J. Kondevat Brandeis University.1 Course Overview and PhilosophyIt is a wonderful time to be thinking about the workings of the living world.Historic advances in molecular biology, structural biology and the use of phys-ical techniques such as optical traps have provided an unprecedented windowon the mechanics of the cell. The aim of this course is to study the cell andits components using whatever tools we need in order to make quantitativeand predictive statements about cellular life. The main intellectual threadof the course will be the idea that the type of quantitative data which isbecoming routine in biology calls for a corresponding quantitative modellingframework. The plan of the course is to elucidate general principles withexciting case studies. Note that science is driven by experiment. Nowhereis this more evident than in the life sciences. As a result, for those that aremost serious I encourage simultaneous enrollment in the laboratory course,APh162 - Physical Biology Laboratory, which will be built around a series ofexperiments which are designed to correspond with material covered in thelecture course APh161.2 Tentative Course OutlineThe course outline given below is intended to provide an overall sense of thetopics we will cover and the general flow of the course. Certain individualtopics might be added or deleted as I see fit.1. Biology - A Feeling for the Numbers• Spatial scales. The size of things - molecules, macromolecularassemblies, organelles, cells, tissues, organisms.2• Temporal scales in cells. How fast? From molecular vibrations todevelopment - a hierarchy of time scales.• Balancing the budget of the cell. Mass budget of the cell. Energybudget of the cell.2. Genome Management• Genomes and the Central Dogma. Information content of genomes(aside on central dogma and “the two great polymer languages”).• Gene Expression. How much, when, where and how fast? Casestudies from metabolism and development. The mechanisms ofgenetic control.• Transcriptional Control. Statistical mechanics of gene expression.The fabled case of the lac operon. Dynamics of gene expression.• Packing the Genome. Physical size of genomes. Packing thegenome in viruses, prokaryotes, eukaryotes.3. The Cell is Crowded!• Inventories and Budgets. Physical content of cells - how manycopies of the various molecular actors in the cellular drama. Themean spacing of molecules.• Getting from here to there. Diffusion in-vivo and in-vitro. Casestudies in cellular life - diffusion to capture, membrane diffusion.Why molecular motors?• Aggregation and Assembly. Crowding and assembly. Case studiesin macromolecular assembly.4. Dynamics in and of Cells• Phenomenology of Cellular Dynamics. Dynamics in the cell. Dy-namics of the cell.• Enzyme dynamics. Phenomenology of enzyme action. Rate equa-tions. Michaelis-Menten dynamics.• Polymerization dynamics. The cytoskeleton is always under con-struction. Dynamics of polymerization. Hijacking the cytoskele-ton - lifestyles of bacterial pathogens. Life at the leading edge.3• Molecular Motors. A rogue’s gallery - translational and rotarymotors. Experimental backdrop. Theories of motor action.5. Processes at Membranes• Membrane Phenomenology. lipids, membrane area, membranecomposition, ions and ion transport.• Membrane structures and deformation. A tour of vesicles andmembranes. The plasma membrane. Mitochondria, the endo-plasmic reticulum and the Golgi apparatus. Modelling membranedeformation - the Helfrich free energy.• Ion Channels. Mechanosensation and tension gating. Action po-tentials and voltage gating.3 BibliographyMy logic in providing the following list of references is to give you a wide viewof some of the important books (both pedagogically and as scholarly works)that have been written to describe this imp ortant field. In addition to theworks listed here, you should count on a steady supply of readings from thecurrent literature. Indeed, this course is going to be reading intensive sincemost of the audience will lack either the biological or physical backgroundand will have to make up for such holes in part through extracurricularreading. One of my main hopes with this list is to avoid flying the flag of anyparticular discipline, whether it be biology, physics or chemistry. We shouldworry less about the names of disciplines and be more open to taking toolsfrom whatever quarter they may be needed.B. Alberts, D. Bray, A. Johnson, J. Lewis, M. Raff, K. Roberts and P. Wal-ter, Essential Cell Biology, Garland Publishing, 2003. This book has becomeone
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