APh161: Physical Biology of the CellWinter 2009When: TTh, 9:00-10:25 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 Stephanie Johnson (x3333, Broad 132,[email protected]), Maja Bialecka (x5761, Broad 71, [email protected])and Steve Privitera x3106, Broad 153, [email protected]). I am alwayshappy to see you, but with certainty, the best way to contact me is by email.After that, the best approach is to schedule a time to see me through myassistant, Linda Scott (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. I will NOT accept ANY latehomeworks (late means anytime after class starts 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 e xplained. 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: The course webpage will have a repository of required reading fromthe original literature. I am particularly persuaded that wide ranging readingwill maximize the value of this course and will be providing a wide varietyof opportunities for you to explore different topics. There is a main text forthe course and two supplementary texts:Physical Biology of the Cell by Rob Phillips, Jane Kondev and JulieTheriot. There will be required readings from this text as well as manyhomeworks that come from the text itself.Chemical Biophysics by D. Beard and H. Qian. This book has many in-teresting insights that complement that presented in the main text.An Introduction to Systems Biology by Uri Alon. This material willconcern the middle part of the course and gives a fantastic view of regulatorybiology.Reading the Story of DNA . This book gives a very nice and interestingdiscussion of the way that our understanding of genomes has transformedbiology.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. In 2009, having just completed my book ”PhysicalBiology of the Cell”, my coauthors and I felt a disappointment that we did2not include any discussion of photosynthesis and electron transfer and theirbasis in quantum mechanics. To that end, the course will push all of us totry and see how simple ideas from quantum mechanics can be used to e xplorehow light energy is harvested by living organisms. Note that science is drivenby experiment. Nowhere is this more evident than in the life sciences. As aresult, for those that are most serious I encourage simultaneous enrollment inthe laboratory course, APh162 - Physical Biology Laboratory, which will bebuilt around a series of experiments which are designed to correspond withmaterial covered in the lecture course APh161.32 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. Lig ht and Life• Inventories and Budgets. To build a cell: and then there waslight. What does it take to make a cell? The lesson of the Keelingcurve.• The story of photosynthesis. The story in words and pictures.Experiments to change your life for.• Quantum Mechanics and Photosynthesis. Background on quan-tum mechanics. Electron gas and tight binding limits. Moleculesthat absorb sunlight. E lectron transfer and tunneling.• Light and Rhythm. Light and the clocks of living organisms. Clas-sic experiments. KaiABC as a model. Bombyx mori and the workof Kai and Nishi.2. Ge nes: Expression, Regul atio n and Management• The story of genomes and their management. Mendel’s abstrac-tion to the human genome. The connection to evolution.• How Cells Decide. Experiments to change your life for: metabolism,developmental decisions, cell fate. Calculating the decision. Bursts,noise and bistability.• Processes of the central dogma. Copying genomes. Gene expres-sion using “thermodynamic models”. Gene expression - dynamics(kinetic proofreading). Genetic switches. Cell cycle oscillator.• Chromosome geography and stochastic decision making. How aregenomes arranged in viruses and cells. Stochastic decision makingand recombination - recombination from viruses to cancer. V(D)Jrecombination and DNA mechanics.• Evolution and cis-regulatory rearrangement. Generating noveltywithout changing coding regions. Case studies: flies to fishes.43. Sig nali ng• Chemotaxis. Phenomenology of chemotaxis. Simple models.• Post-Translational Protein Modification. Phenomenology of phos-phorylation. Case studies and simple models.• Physical limits of signaling. Generating sharp features in em-bryos.• Mechanosensation. Examples of mechanosensation. A bacterialcase study. Toxins and membrane proteins.• Electrical Signaling in Cells. How cells talk. Biological electricity.The action potential.4. Bio lo gy’ s Greatest Idea: Evolution• Was Dobzhansky Right? ”Nothing in biology makes sense exceptin the light of evolution”. Anatomy, fossils, genomes, structures.Experiments and observations to change your life for: from fins tolimbs, evolution in real time, sticklebacks.• The Revolution Continues. Genome sequences and evolution. Anew domain of life. Horizontal gene transfer.•
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