Class Meetings
Mon Wed Fri, 5^th period
11:45 am -12:35 pm

Mon/Fri (lecture): Room 1200 NPB (small classroom near Student Services office)
Wed (journal club): Room 2205 NPB (Physics main conference room)

Instructor:
Prof. S.J. Hagen
Tel.: (352) 392-4716
Office: 2362 New Physics Building
Office Hours: to be announced ...

Website:
The main website for this course is maintained on the UF Sakai System. Readings, announcements, and other important materials will be posted there. Click on the link and then log in to Sakai with your gatorlink username & password. The instructor will assume that all students check the Sakai website regularly for important news and information.

Description: This is a graduate level introduction to principles of biological physics. The course is appropriate for all physics graduate students - no background in biology is required. This year the course will focus on the design and dynamics of biological networks, including gene regulatory networks. We will apply physical, mathematical, and biological concepts to construct quantitative models for understanding real signaling and transcription networks in biological systems. In addition to the systems biology focus, the course will also include readings of classic papers in related areas of biological physics.

Finally, please note that this course emphasizes the quantitative physical/mathematical perspective on biological networks. It is not intended as a general introduction to biology. If you are looking for an Intro Bio course then look elsewhere.

Format:
The format will consist of lecture (2 hrs per week) plus journal club (1 hr/week). At our lecture meetings (Mondays & Fridays) we will discuss topics in quantitative biology, following the textbook by U.Alon (see below). However Alon's book is not really a biology book. Strictly speaking it is not a biological physics book either. It is primarily an introduction to the function and engineering of networked objects, which happen to be genes. Earlier chapters deal with very general engineering ideas, while later chapters deal in some biological examples. So we will have to fill in a lot of the biological context through readings of classic (and near-classic) research papers in biological physics. Students will present and discuss these papers at our journal club meetings (Wednesdays).

Textbooks
(1) Required:

An Introduction to Systems Biology: Design Principles of Biological Circuits,
by Uri Alon.
Chapman & Hall/CRC (2007)
ISBN-13: 978-1584886426
One copy is available through 2-hr reserve at Marston Science Library
Author's webpage
Book review (Nature)
Book review (Physics Today)

(2)Also recommended (but optional):

Berg, H.C. Random Walks in Biology
Nelson, P., Biological Physics: Energy, Information, Life
Phillips, R., Kondev, J., Theriot, J. Physical Biology of the Cell
Sneppen K. & Zocchi G. Physics in Molecular Biology

Grading & Homework
This course is intended to stimulate and cultivate your interest in biological physics, not to crush you with a heavy workload. However, you are definitely not going to learn anything if you do not read the assigned materials, which include the textbook by U.Alon and the articles presented in the journal club. Therefore we will (1) employ some form of regular quiz or assessment to verify that students are reading the journal club articles. We will also (2) give occasional homework assignments based on the chapter problems from U.Alon's book. Finally, each student will be expected to (3) present one article at the journal club. The actual grading weights assigned to these three portions will be announced later. Whether we also have (4) a final exam will depend on how people have performed on the regular assessments; clearly if people have kept up with the reading it is not as necessary to have a final exam.

Make-ups
The grading scheme will provide some leeway for students who have had to miss one or two quizzes due to personal emergency. However a student who misses class on multiple occasions will not receive any type of make-up or other accomodation. As class attendance is definitely expected, make-ups are not available for missed work.

Auditing:
Students may not audit the lecture portion of this course. You must enroll for credit. There is however a journal club portion of the course, which meets once weekly. All interested parties are welcome to attend the journal club, whether registered or not. With the permission of the Instructor, a student may enroll only in the journal club (section 8686) for one credit.

Journal Club Calendar:
The journal club meets on Wednesdays and it makes up one third of this course. Unlike the lecture portion it is open to everyone (whether enrolled in PHY7097 or not). Each meeting will consist of one student presenting one paper, although some longer papers may require two students presenting over two Wednesdays. All enrolled students are expected to read the presented papers prior to class and then arrive prepared for discussion. A list of suitable articles will be provided at the beginning of the semester, so that students may choose the articles and dates for their presentations. Journal club meetings are in room 2205 NPB.

In class we will discuss expectations and guidelines for the journal presentations. In general, however, your presentation should aim to explain the basic ideas behind the journal article: the motivation, the method, the findings and results. Take a tutorial approach and try to deliver a clear, organized explanation of the key ideas. It is far better to give a clear explanation of a few main points than to make a confusing mess of a large number of details. Your talk should run for about 35-40 minutes, which allows about 10-15 minutes for questions and discussion. Do not run overtime. Before you begin preparing your presentation, seek out some good advice on how to give a good talk: there is plenty of such advice available online.

Aug 25 - organizational meeting
Sep 1 - Luis Colon-Perez
J.J. Hopfield, Neural networks and physical ... (1982).
Sep 8 - Yitzi Calm
H.H. McAdams & A.Arkin, Stochastic mechanisms in gene expression ... (1997).
Sep 15 - Gabriel Dilanji
M. Chalfie, Green fluorescent protein ... (1994).
Sep 22 - Adam Sandwell
E.M. Ozbudak et al., Regulation of noise in the expression ... (2002).
Sep 29 - Naween Anand
J.J. Hopfield, Kinetic proofreading ... (1974).
Oct 6 - Natali Di Russo
B. Palsson, Metabolomic systems biology ... (2009).
Oct 13 - Elizabeth Knowles
G.J. Stephens, Dimensionality and dynamics in ... (2008).
Oct 20 - Marcus Peprah
D. Wang & S. Bodovitz, Single cell analysis: the new frontier in 'omics' ... (2010).
Oct 27 - Kyle Heim
J.K. Nicholson, The challenges of modelling ... (2004).
Nov 3 - Wenya Wang
E. Holmes, Human metabolic phenotype ... (2008).
Nov 10 - Gregory Stupp
T. Long, Quantifying the integration of quorum-sensing ... (2009).
Nov 17 - Evan Thatcher
I. Mihalcescu, Resilient circadian oscillator ... (2004).
Nov 24 - no class
Dec 1 - Douglas Rank
H.C. Berg, Motile behavior of bacteria ... (2000).
Dec 8 - Minjun Son
C.E. Shannon, A mathematical theory of communication ... (1948).

Journal Club Readings:
The following articles are suggested or recommended for journal club presentation. Some are original research articles and some are review articles. The list is subdivided crudely by topic, although please read the abstract if you want to know what a paper is really about. We will not read all of these papers, because we will only have ~14-15 journal club meetings in Fall 2010 and we can only cover (at most) one article per meeting. Each student will select one paper (or half of a long paper) and spend one class period presenting that paper to the class.
Be sure to select a paper that you truly find interesting. Do not make the mistake of assuming that the shortest paper on the list will be the easiest to present, or that the longest paper will be the most difficult. You will regret that mistake. Be careful about selecting a review paper if you are completely unfamiliar with the topic, as the breadth of the review may increase the number of terms, concepts, and mechanisms that you will be expected to explain in your presentation. On the other hand, you will learn more if you take on a greater challenge. If you do not like any of these papers and you wish to present an article that is not on this list, you will need to discuss (and thoroughly justify) your choice with me before you start working on your presentation.

Biological kinetics

J.J. Hopfield, Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity, Proc Nat Acad Sci USA 71 4135-4139 (1974).
S. Klumpp, Z. Zhang, and T. Hwa, Growth rate-dependent global effects on gene expression in bacteria, Cell 130, 1366-1375 (2009).
M. Scott, C.W. Gunderson, E.M. Mateescu, Z. Zhang, and T. Hwa, Interdependence of cell growth and gene expression: origins and consequences, Science 330 1099-1102 (2010).

U. Alon, M. G. Surette, N. Barkai and S. Leibler, Robustness in bacterial chemotaxis, Nature 397 168-171 (1999).
H.C. Berg, Motile behavior of bacteria, Physics Today 53 24-29 (2000) .
H.C. Berg and E.M. Purcell, Physics of chemoreception, Biophys J. 20 193-219 (1977).
D. Bray, M.D. Levin, K. Lipkow, Chemotactic behavior of computer-based surrogate bacteria, Current Biology 17 12-19 (2007).
G.J. Stephens, B. Johnson-Kerner, W. Bialek, W.S. Ryu, Dimensionality and Dynamics in the Behavior of C. elegans, PLoS Computational Biology, 4 e1000028 (2008)

C.E. Shannon, A mathematical theory of communication, The Bell System Technical Journal, 27 379-423, 623-656, (1948). See also this review.
T.D. Schneider, G.D. Stormo, L. Gold, and A. Ehrenfeucht, Information content of binding sites on nucleotide sequences, J . Molec. Biol. 188 415-431 (1986).

M. Chalfie, Y.Tu, G.Euskirchen, W.W. Ward, D.C. Prasher, Green fluorescent protein as a marker for gene expression, Science 263 802-805 (1994).
D.T. Gillespie, Exact stochastic simulation of coupled chemical reactions, J. Phys. Chem . 81 2340-2361 (1977).
T.D. Schneider, G.D. Stormo, L. Gold, and A. Ehrenfeucht, Information content of binding sites on nucleotide sequences, J . Molec. Biol. 188 415-431 (1986).

E. Holmes et al., Human metabolic phenotype diversity and its association with diet and blood pressure, Nature 453 396-401 (2008).
J.C. Lindon & J.K. Nicholson, Spectroscopic and Statistical Techniques for Information Recovery in Metabonomics and Metabolomics (review), Annu. Rev. Anal. Chem. 1 45-69 (2008).
J.K. Nicholson, E. Holmes, J.C. Lindon, I.D. Wilson, The challenges of modelling mammalian biocomplexity (review), Nature Biotechnology 22 1268 (2004).
B. Palsson, Metabolomic systems biology (review), FEBS Letters 583 3900-3904 (2009).
D. Wang & S. Bodovitz, Single cell analysis: the new frontier in 'omics' (review), Trends in Biotechnology 28 281-290 (2010).

M.B.Elowitz & S.Leibler, A synthetic oscillatory network of transcriptional regulators, Nature 403 335-338 (2000).
J.J. Hopfield, Neural networks and physical systems with emergent collective computational abilities, Proc Natl Acad Sci USA 79 2554-2558 (1982).
Long T, Tu KC, Wang Y, Mehta P, Ong NP, Bassler BL, Wingreen NS, Quantifying the integration of quorum-sensing signals with single-cell resolution, PLoS Biol. 7 e68 (2009). PMCID: 2661960.
I. Mihalcescu, W. Hsing, S. Leibler, Resilient circadian oscillator revealed in individual cyanobacteria, Nature 430 81-85 (2004). See also this commentary.
M. Nakajima, K. Imai, H. Ito, T. Nishiwaki, Y. Murayama, H. Iwasaki, T. Oyam a, T. Kondo, Reconstitution of Circadian Oscillation of Cyanobacterial KaiC Phosphorylation in Vitro Science 308, 414-415 (2005). See also Commentary and the proposed model by van Zon et al. (below).
J.S. van Zon, D.K. Lubensky, P.R.H. Altena, P.R. ten Wolde, An allosteric model of circadian KaiC phosphorylation, Proc. Natl. Acad. Sci. USA 104 7420 (2007).

N.Q. Balaban, J. Merrin, R. Chait, L. Kowalik, S. Leibler, Bacterial persistence as a phenotypic switch, Science 305 1622-1625 (2004).
M.B. Elowitz, A.J. Levine, E.D. Siggia, P.P. Swain, Stochastic gene expression in a single cell, Science 297 1183-1186 (2002).
H.H. McAdams and A. Arkin, Stochastic mechanisms in gene expression, Proc Nat Acad Sci USA, 94 814-819 (1997).
E. M. Ozbudak, M. Thattai, I. Kurtser, A. D. Grossman, and A. van Oudenaarden, Regulation of noise in the expression of a single gene, Nature Genetics 31 69- (2002). See also Commentary.

T.J. Nelson, Physics envy among biologists: fact or fiction?, Science Creative Quarterly (2009).

Websites
Biofundamentals at UC Boulder
Systems Biology at PNNL
Biophysical Structures (Biophysical Society online textbook)
Biophysical Mechanisms (Biophysical Society online textbook)
Advice on scientific writing
Calibrated Peer Review

Disabilities, Academic Honesty, etc.
The instructor adheres slavishly to UF policies on academic honesty, student conduct, religious accomodations, and disability accomodations. Please refer to the website of the Dean of Students Office for a clear presentation of these policies and the Student Conduct Code. Academic honesty violations in particular are deemed especially serious at the graduate level and will likely be catastrophic for your UF career. If you are unclear on any aspect of these policies, please talk with the instructor.

Attendance
Regular attendance and participation is definitely expected. Do not enroll in this course if you cannot attend class.