APh161: Physical Biology of the CellWinter 2006When: TTh, 8:30-10:00 AM. We will have an aggressive set of makeup lec-tures right from the start of the term since I will miss class several timesduring the term.Who: You and me (Rob Phillips, x 3374, [email protected], 159Broad). The TAs for the course are Eric Peterson, x5876, [email protected] Broad and Jen Barnet, x 6015, [email protected] 122 Braun. I am al-ways happy to see you, but with certainty, the best way to contact me is byemail. After that, the best approach is to schedule a time to s ee me throughmy assistant, 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-of-term poster during the class poster session. I will NOT accept ANY latehomeworks (late means anytime after class is over the day the homework isdue) unless you have a mindblowingly good excuse - this means a note fromsomeone like a doctor or a Dean. (Please do not even ask me for an exten-sion - the answer is NO). As for collaboration, you may discuss the homeworkwith others, but your explanations and derivations must be your own andyour logic should be carefully explained and the significance of your resultsshould also be explained. If you hand us a sloppy (either sloppy thinking orwriting) homework the grader will likely be unable to penetrate your logic1and you will lose points.Reading: 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 Alb erts et al., and b) Physical Biologyof the Cell, an incomplete draft of a book that I am writing w ith J. Kondevat Brandeis University and Julie Theriot of Stanford University. The bookwill be made available online as we go along.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 Numbers2• Spatial scales. The size of things - molecules, macromolecularassemblies, organelles, cells, tissues, organisms.• 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. The fabled case of the lambdaswitch. Dynamics of gene expression.• Biological Accuracy. Error rates during translation. Kinetic proof-reading.• Packing the Genome. Physical size of genomes. Packing thegenome in viruses, prokaryotes, eukaryotes.• DNA Management During the Cell Cycle. The cell cycle. Themachines of replication. Chromosomal territories and DNA seg-regation. The case of ParM and plasmid s egregation during celldivision.3. 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.• Molecular Motors. A rogue’s gallery - translational and rotarymotors. Experimental backdrop. What is a muscle and how doesit work? Theories of motor action. The case of kinesin. Trafficwithin cells.34. Processes at Membranes• Membrane Phenomenology. lipids, membrane area, membranecomposition, ions and ion transport.• Membrane structures and deformation. A tour of ves icles andmembranes. The plasma membrane. Mitochondria, the endo-plasmic reticulum and the Golgi apparatus. Modelling membranedeformation - the Helfrich free energy. Curvature management -making vesicles, viral budding and beyond.• Ion Channels. Mechanosensation and tension gating. Action po-tentials and voltage gating.5. Miscellany on Physical Biology• Motility. Physical content of cells - how many copies of the vari-ous molecular actors in the cellular drama. The mean spacing ofmolecules.• Signaling and Chemotaxis. Phenomenology of signaling. Statisti-cal mechanics of snip and s titch. The case of chemotaxis.• Building a Fly. Bringing the whole course home through the ex-ample of a fly and the development of an embryo. Transcriptionfactors and the fly body plan. Diffusion in embryos.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 important fie ld. 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
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