Biological Dynamics, APC/EEB/MOL/PHY 514
Lectures: Tuesdays, Thursdays, 1:30-2:50pm, starting Sept. 9 (org. meeting)
Carl Icahn Laboratory, Room 200
Computer Labs: Thursdays, 3:00-4:20PM, starting Sept. 16
BWF Computer Cluster (Carl Icahn Lab, Room 131)
Course Webpage: www.math.princeton.edu/apc514
This course is an introduction to the methods used to describe and understand biological dynamics using mathematical models and computer simulation. There will be four main units:
· Section 1: Control of Gene Expression, Curtis Callan (Physics), Saeed Tavazoie (Mol. Bio.)
· Section 2: Ecological and Epidemiological Dynamics, Simon A Levin (EEB), Jonathan Dushoff (EEB), Joshua Weitz (EEB)
· Section 3: Signaling, Chemotaxis, Cell Cycle Models, Will Ryu (Lewis Sigler Institute), Ned Wingreen (Mol. Bio.), Chao Tang (NEC)
· Section 4: Morphogenesis, Spatial Patterns in Development, Stas Y. Shvartsman Chem. Eng.), Eric F. Wieschaus (Mol. Bio.), Trudi Schupbach (Mol. Bio.),
perhaps guest lecturers) and a computer laboratory/ homework problem component.
Questions? The following is the contact information for the course TA and for the principal lecturers in the different sections:
Course Teaching Assistant (TA):
Office: 221 Fine Hall
Office: 334 Jadwin Hall Office: 245 Carl Icahn Lab
Phone: 258-4321 Phone: 258-0331
Section 2: Ecological and Epidemiological Dynamics
Jonathan G. Dushoff Simon Levin
Office: 201 Eno Hall Office: 203 Eno Hall
Phone: 258-6882 Phone: 258-6880
Office: 201 Eno Hall
Section 3: Signaling, Chemotaxis, Cell Cycle Models
Ned Wingreen Will Ryu
Office: 347 Lewis Thomas lab Office: 119 Carl Icahn Lab
Phone: 258-8476 Phone: 258-8129
Section 4: Morphogenesis, Spatial Patterns in Development
Stas Shvartsman Eric Wieschaus
Office: 248 Carl Icahn Lab Office: 435 Moffett
Phone: 258-4694 Phone: 258-5383
No background in the relevant biology is required. However, a solid preparation in mathematics, including differential equations, integral calculus, and linear algebra is essential, as is some experience in using mathematics to model the real world. Graduate students with undergraduate degrees in mathematics, physics, electrical engineering, mathematical biology, and biophysics will have such backgrounds, as should Princeton seniors with these majors. Problem sets, which will frequently involve computer simulation exercises, are an important component of the course. Instruction and help will be available in a computer laboratory. Previous experience with computers is not essential, but the student will need to learn useful aspects of MATLAB and other programs for scientific computation.
There is no single book which covers all of the topics in this course. The following
general books, which will be useful at various times, have been requested for placement on reserve in Fine Library. Some of these books may be on reserve for other classes (see possible cross-listings below).
engineers, Reserve APC/EEB/MOL 514
The lectures will often draw upon material in specific research articles, many of which are listed in the schedule. In most cases, pdf files of the articles will be posted on the course website. Where appropriate, a paper copy will be distributed in class or made available to be photocopied, location TBA.
There will be one to two homework sets per unit. These may involve computer simulations, and the necessary background will be provided in the lectures and in the
computer labs taught by the Course TA. Assignments will be put on the course
webpage. The homework will be due at the time given on the assignments, typically at the start of class, and must be handed in on time. Solution sets will be posted on the course webpage shortly after the due date.
As a culminating experience, each registered student should describe a research proposal based on the material covered in the lectures for APC514 in a two page (no more!) proposal due (in pdf format, via email to firstname.lastname@example.org) by 5 PM on Tues., January 11, 2005. We must be strict on this “Dean’s Date” deadline. The proposal should describe the present state of knowledge, where there is a lack of understanding, and how that gap could be filled by particular experiments, mathematical analysis, or simulations with a two month research effort. The point is for the students to move from the problem sets to asking their own questions, and to ask not only what is a great question, but what is a more modest solvable question. We also want to continue the building of a community of people interested in biological dynamics, and hope through this ``proposal'' mechanism to enhance the future interactions of the group of us on a variety of topics. We’ll have informal presentations of the project ideas (~5 mins. per student) about a week later which will provide a chance for friendly feedback and discussion. We’ll hand out more details as the time comes closer.
Students will have the option of taking the course on a letter grade or pass/fail basis. Note, however, that pass/fail does not correspond to a “free ride,” and students are expected to complete all homework assignments in order to pass. The course grade will be based on homework assignments and the written and oral presentation of the course mini-project.
A roster including email addresses will be compiled at the first few lectures so that students can be contacted with important announcements and homework tips. (If you have a suggestion which you feel should be circulated to fellow students, please contact the Course TA, who will do so at his discretion.)
Computer labs will meet Thursdays 3:00-4:20 PM (starting Sept. 16) in the BWF computer cluster (CIL 131). The computer labs will cover supplemental material to the lectures. Students are also encouraged to ask questions about the lectures and homework assignments during the computer labs.
In addition to the computer labs, the Course TA will be available to answer questions
at times to be arranged. Also, feel free to email the Course TA with questions. The lecturers will also be available for consultation by appointment.
Each registered student will get a computer account on the BWF Linux cluster (CIL 131). MATLAB, a computing environment that combines numeric computation, graphics and visualization, and a high-level programming language is installed on these computers. MATLAB will be useful for the homework assignments and the computer tutorials.
Schedule for APC/EEB/MOL 514, Fall 2004
The journal articles cited in the reading list will, in general, be available for download from the course website. Books will be on reserve in Fine Library as will be some of the articles. The Sept. 9 class meeting will be devoted to organizational matters.
Unit 1: Control of Gene Expression
Lecturers: Curtis Callan (Physics), Saeed Tavazoie (Mol. Bio.)
Sept. 14th. Lecture 1 (Tavazoie): High-level introduction to molecular biology, genome organization, information flow in the cell, regulation of cellular behavior, molecular networks.
Sept. 16th. Lecture 2 (Tavazoie): Core mechanisms of transcriptional regulation, making observations, high-throughput technologies for measuring mRNA expression, microarray analysis, finding patterns in expression data
Sept. 21st. Lecture 3 (Callan): The dynamics and statistical mechanics of transcription factor binding to specific sites on DNA. The bioinformatics and statistical mechanics of identifying transcription factor binding sites.
Sept. 23rd. Lecture 4 (Callan ): The dynamics of transcription factor control of gene expression. Modeling of classic examples (phage and lac) of simple genetic switches. Addressing the issues of small numbers, fluctuations, stability.
Sept. 28th. Lecture 5 (Tavazoie): Systematic approaches for mapping transcriptional regulatory interactions, expression patterns and motifs, linear modeling, Bayesian networks, combinatorial regulation
Sept. 30th. Lecture 6 (Callan): TBD. Discussion of the problems of modeling gene regulation networks? Discussion in greater depth of issues from Lects. 3 and 4?
Unit 2: Ecological and Epidemiological Dynamics
Lecturers: Johnathan Dushoff (EEB), Simon Levin (EEB) and
Joshua Weitz (EEB)
Oct. 5th , Lecture 2 (Weitz):. An introduction to the theoretical foundations of scaling: dimensional analysis, self-similarity, the Pi-theorem, methods to construct scaling hypotheses, and the scaling collapse in practice. This will be followed by an overview of scaling in biology, drawing from examples in terrestrial and marine systemswith emphasis on the structure and function of organisms.
Oct. 7th , Lecture 3 (Weitz): Application of scaling to problems in ecology with emphasis on recent developments in the study of the allometric scaling of metabolic rate. Empirical and theoretical studies of the scaling of metabolic rate will be reviewed, along with attempts to unify observations of the organization of ecological communities (population density, size distributions, stoichiometric relations) via fundamental principles of energy use.
Oct. 12th , Lecture 1 (Levin): Ecosystems and the biosphere as complex adaptive systems: a study of the interplay among processes operating at diverse scales of space, time and organizational complexity. The key to such a study is an understanding of the interrelationships between microscopic processes and macroscopic patterns, and the evolutionary forces that shape systems. In particular, for ecosystems and socioeconomic systems, much interest is focused on broad scale features such as diversity and resiliency, while evolution operates most powerfully at the level of individual agents. Understanding the evolution and development of complex adaptive systems thus involves understanding how cooperation, coalitions and networks of interaction emerge from individual behaviors and feed back to influence those behaviors.
Oct. 14th , Lecture 4 (Levin): On the evolution of culture and other diseases. We will introduce the dynamics of disease, and draw analogies for the dynamics of social norms.
Oct. 19th, Lecture 5 (Dushoff): Introduction to the dynamics of infectious diseases
Oct. 21st, Lecture 6 (Dushoff): Pathogen evolution and dynamics
Unit 3: Signaling, Chemotaxis,Cell Cycle Models
Lecturers: Will Ryu (Lewis Sigler Inst.), Ned Wingreen (Mol. Bio.),
Chao Tang (NEC)
Nov. 2nd , Lecture 1 (Ryu): General overview of bacterial chemotaxis: historical perspective, how bacteria swim, general chemotactic strategy, genetics and biochemistry, information flow.
Nov. 4th , Lecture 2 (Ryu): Physics of chemotaxis: Life at low Reynolds number, limits and benefits of diffusion, physics of chemoreception.
Nov. 9th , Lecture 3 (Ryu): Biophysical measurements and models of chemotactic response (I): response to temporal gradients, impulse response, adaptation, sensitivity.
Nov. 11th , Lecture 4 (Wingreen): Biophysical measurements and models of chemotactic response (II): robustness, sensitivity revisited.
Nov. 16th, Lecture 5 (Wingreen): Modeling min-protein oscillations.
Nov. 18th, Lecture 6 (Tang): Cell cycle of the budding yeast.
Unit 4: Spatial Patterns in Development
Lecturers: Trudi Schupbach (Mol. Bio.), Eric Wieschaus (Mol. Bio.),
Stas Shvartsman (ChemE & Genomics)
Nov. 23rd and 30th, Lectures 1-2 (Shvartsman): Cell-cell communication networks in development. Feedback in pattern formation. Examples from Drosophila development.
Dec. 2nd Lecture 3 (Wieschaus) Overview of development and key questions requiring quantitative models; development of the body plan in Drososphila.
Dec. 7th, Lecture 4 (Schupbach): Drosophila oogenesis.
Dec. 9th, Lecture 5 (Shvartsman): Transcriptional profiling of developing systems.
· Gurdon JB, Bourillot PY. Morphogen gradient interpretation. Nature. 2001, 413(6858):797-803.
· Freeman M. Feedback control of intercellular signaling in development. Nature. 2000, 408(6810):313-9.
· Pires-daSilva A, Sommer RJ. The evolution of signaling pathways in animal development. Nat Rev Genet. 2003;4(1):39-49.