PHYS 320: Biological Physics Fall 2015, 3 Credits Department of Physics, Case Western Reserve University Instructor Class Format Prof. Michael Hinczewski Lectures: MWF 2:00 2:50pm email: [email protected] Office Hours: TBD office: Rockefeller 105A Course Description This course explores the intersection of physics and biology: how do fundamental physical laws constrain life processes inside the cell, shaping biological organization and dynamics? We will start at the molecular level, introducing the basic ideas of nonequilibrium statistical physics and thermodynamics required to describe the fluctuating environment of the cell. This allow us to build up a theoretical framework for a variety of elaborate cellular machines: the molecular motors driving cell movement, the chaperones that assist protein folding, the informationprocessing circuitry of genetic regulatory networks. The emphasis throughout will be on simple, quantitative models that can tackle the inherent randomness and variability of cellular phenomena. We will also examine how to verify these models through the rich toolbox of biophysical experimental and computational technologies. The course should be accessible to students from diverse backgrounds in the physical and life sciences: we will explain both the biological details and develop the necessary mathematical / physical ideas in a selfcontained manner. Prerequisites MATH122 or MATH124; ENGR131 or EECS132 Learning Outcomes After completing the course, a student should be able to: ● Understand the pervasive role of thermal fluctuations in biological processes at the nanoscale, and how this necessitates a probabilistic description of cellular dynamics. ● Have fluency in the basic mathematical tools (like the master equation) that describe how the probabilities of biophysical observables change in time. ● Describe how entropy and the second law of thermodynamics impact the functioning of biological systems. ● Construct, solve (either analytically or numerically), and interpret the results of a stochastic, dynamical model for a biochemical reaction cycle. ● Identify the kinds of biomolecular properties that are measurable using modern experimental labeling and imaging techniques. ● Program a script that takes data from a biophysical experiment (i.e. the position vs. time trajectory of a fluorescently labeled molecule) and analyzes it by fitting to an analytical model. Reading Materials The textbook for the course will be Physical Biology of the Cell by Rob Phillips et al. (2nd edition, Garland Science, 2013). Additional resources from the research literature will be introduced as needed, particularly in the case of the homework assignments. Homework The weekly problem sets are the heart of the course, allowing students to get a firsthand experience in applying the ideas introduced during lectures to actual research problems. Each assignment will consist of a series of related exercises organized around a single topic, drawn from a theoretical or experimental paper in the recent biophysics literature. Some problem sets will involve purely analytical calculations to understand a particular model, while others will also require numerical approaches, for example analyzing sample experimental data sets posted online or running a simple kinetic Monte Carlo simulation. In the latter cases, the only necessary programming resources are those already familiar to the students through ENGR131 or ENGR132. Collaboration on the homeworks is encouraged, though each student must write up their solutions individually. Comprehensive, detailed answers will be posted after the homework deadline, and these will be essential course materials to complement the lectures and textbook readings. Exams One inclass midterm will be given before the fall break, as well as a final exam. Questions will be drawn both from material in the lectures and topics covered by the problem sets. Grading The course grade will be determined by performance in the following categories: Problem sets (10 sets x 7%): 70% Midterm exam: 15% Final exam: 15% Class Schedule Week Topics Readings / Homeworks 1: 8/25, 8/27 Setting the stage: “jiggling and Chap. 13 wiggling” within the crowded cell. Random walks, diffusion, constraints on biological time / length scales. 2: 9/1, 9/3 Random walks in energy space: the Chap. 6 master equation, detailed balance, Problem Set #1 due. and the canonical ensemble. 3: 9/8, 9/10 Producing and degrading: the theory of stochastic reaction dynamics. 4: 9/15, 9/17 Reaction dynamics in action: how to Chap. 15 grow a cytoskeletal filament. Problem Set #3 due. 5: 9/22, 9/24 Beating the diffusion speed limit: molecular motors. Chap. 16 Problem Set #4 due. 6: 9/29, 10/1 Paying the price: directed motion, the second law of thermodynamics, and the need for external energy sources. Chap. 16 Problem Set #5 due. 7: 10/6, 10/8 Inventing the wheel: rotary motors (ATP synthase, bacterial flagellar motors). Chap. 16 / Chap. 12 Midterm exam. 8: 10/13, 10/15 Getting ahead: motordriven cell motility in a low Reynolds number world. Chap. 12 9: 10/27, 10/29 Random walks revisited: flexible biopolymers and the protein folding problem. Chap. 8 Problem Set #6 due. 10: 11/3, 11/5 The difficulties of getting into shape: protein misfolding, aggregation, neurodegenerative diseases, and the role of chaperones. Chap. 8 Problem Set #7 due. Chap. 15 Problem Set #2 due. 11: 11/10, 11/12 The difficulties of getting bent out of shape: stiff biopolymers and the physics of DNA packing. Chap. 10 Problem Set #8 due. 12: 11/17, 11/19 ProteinDNA interactions: facilitated Chap. 19 diffusion and DNA looping. Problem Set #9 due. 13: 11/24 Noisy dynamics of genetic regulation. Chap. 19 14: 12/1, 12/3 Coping with the noise: transmitting information through biochemical networks. Chap. 19 Problem Set #10 due.