BE/APh161: Physical Biology of theCellWinter 2010When: TTh, 8:30-10:25 AM. Because I will be on travel several times through-out the term, the hours are set so that we don’t have to do makeup lectures.Who: You and me (Rob Phillips, x 3374, [email protected], 159Broad). The TAs for the course are Stephanie Johnson (x3333, Broad 132,[email protected]), Linda Song ( [email protected]) and Chao Liu([email protected]). I am always happy to see you, but with cer-tainty, the best way to contact me is by email. After that, the best approachis to schedule a time to see me through my assistant, Katie Miller (x6337,[email protected], 138 Broad).Where: 24 BBBWhat: 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 explained. If you hand us a sloppy (either sloppy thinking or1writing) homework the grader will likely be unable to penetrate your logicand 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 variety ofopportunities for you to explore different topics. There are two main textsfor the course:A Feeling for the Numbers in Biology by Ron Milo and Rob Phillips.This book is in the early stages of being written and is meant to complementthe recently developed BioNumbers website (http://bionumbers.hms.harvard.edu/).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.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 didnot 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 explorehow light energy is harvested by living organisms. Note that science is drivenby experiment. Nowhere is this more evident than in the life sciences. As a2result, 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 APh161.2 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. This list is intended to give asense of the scope of both what I would like to cover and what I think youshould know about. I will assign a lot of reading that builds foundations inthe key ideas that I wish to cover and I fully expect you to take the readingassignments seriously.1. A Feeling for the Numbers in Biology (Week of Jan. 4)• Inventories and Budgets. Sizes of molecules, organelles and cells.Concentrations of key molecular players ranging from ions to macro-molecules.• The Rate of Things in Biology. The cell cycle. The rates of thecentral dogma. Motors and channels.• Energies and Forces. The energy currencies of the cell. Typicalforce scales.• Information Management. The genetic code. Genome sizes. En-coding information in signals and gradients.2. Signaling (Week of Jan. 11)• Electrical Signaling in Cells. How cells talk. Biological electricity.Ion channels. The action potential.• Post-Translational Protein Modification. Phenomenology of phos-phorylation. Case studies and simple models.• Chemotaxis. Phenomenology of chemotaxis. The two-componentsignal transduction system. Simple models.3• Eukaryotic cell motility. phenomenology of actin protrusions. N-Wasp and Arp2/3. Dual input binding. Tether length as a knob.• Mechanosensation. Examples of mechanosensation. Osmotic shock.A bacterial case study. Toxins and membrane proteins.3. Genes: Expression, Regulation and Management (Weeks ofJan. 18 and Jan. 25)• 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.4. Patterning in Biology (Week of Feb. 8)• Phenomenology of Patterns in Biology. Patterns in space andtime. Patterns in unicellular organisms. Patterns in multicellularorganisms.• Physical limits of signaling. Generating sharp features in em-bryos.• The Turing concept. How can a “wrong” model be so
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