BE 150/Bi 250b project ideas, Winter 2013

Digit patterning (MBE)

• Paper: Hox Genes Regulate Digit Patterning by Controlling the Wavelength of a Turing-Type Mechanism by Sheth and Marco, et al, Science Dec 2012

• Idea: build a reaction diffusion model to replicate the results in the paper, showing how multiple digit patterns can be generated in mice. Show how to tune the number of digits on the hand by progressively removing copies of a hox gene. Discuss this as evidence for a turing type patterning process (with modeling).

Scaling of embryonic patterning (MBE)

• Paper: Scaling of embryonic patterning based on phase-gradient encoding by Lauschke and Tsiairis et al, Nature Jan 2013.

• Idea: paper shows an ex vivo model of the presomitic mesoderm wave propagation system for simile patterning, ie they cut some of these cells out from the mouse embryo and show that they can still make segments similar to in vivo. They then use the system to show that there is scaling of number and size of segments with overall explant size.

Robustness and tunability comparison for synthetic oscillators (RMM)

• Papers: Elowitz and Leibler, Stricker et al, Danino et al, Nimfa 2004

• Idea: put together models of different types of oscillators in E. coli using consistent parameters. Explore parameter sensitivity, noise attenuation and behavioral diversity in each and comment on the relevant robustness and tunability processes.

Robustness and loading effects in MAPK cascades (RMM)

• Papers: TBD

• Idea: In class we showed that one of the advantages of a two component signaling system and multi-stage MAPK cascades is that you can get higher input/output gain. Another potential benefit of such constructs may be the robustness to downstream loads as well as insensitivity to noise and parameters. Construct models of a set of different signalling mechanisms and explore some of these tradeoffs.

Feedback loops operating at different time scales (EDLS)

• Paper: Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells. Ping Wei*, Wilson W. Wong*, Jason S. Park, Ethan E. Corcoran, Sergio G. Peisajovich, James J. Onuffer, Arthur Weiss, Wendell A. Lim. Nature 488, 384–388 (2012)

• Idea: Explore feedback loops operating on different time scales and look at the effect of this on pulses with different frequencies. Need to flesh this out a bit more but you can do a bunch of things like looking what happens if you combine the feedback loops, or looking at the entire frequency response curve or doing sensitivity analysis on the different parameters. The model in the paper was built off from:

• • Zi, Z., Liebermeister, W. & Klipp, E. A quantitative study of the Hog1 MAPK response to fluctuating osmotic stress in Saccharomyces cerevisiae. PloS one 5, e9522 (2010).

Utilization of a conserved resource (EDLS)

• Like Dan's ACC paper

Asymmetric positive feedback (VH)

• Paper: http://www.nature.com/msb/journal/v8/n1/full/msb201210.html
• Idea: Positive feedback is one of the central components of biological circuits. In this paper by Ratushny et al, they analyze the effects of having asymmetrical positive feedback loops, in which only one of the molecules in a heterodimer is self-upregulates. In the paper, they mention a number of biological systems with this circuit motif. Choose one of the examples which is not demonstrated in the paper with which to perform a thorough analysis. Model the system to include additional features other than the ASSURE system and compare that to a model in which there is symmetrical upregulation. How does this affect the behavior of your system? What implications does it have for the organism as a whole?

Propose you own project (RMM)

Guidelines: propose a project that involves reading a set of papers in the literature and performing some modeling and analysis to propose a testable hypothesis about the behavior of the system you investigate. Your writeup should include a list of 1-3 papers along with a short (1-2 sentence summary of their main results), followed by a 1-2 paragraph description of the question you propose to explore. All proposals must be submitted by a 2 person team, ideally with one student in Bi 250b and one student in BE 150.