Project 2: Theoretical analysis of functional modules (Fisher, years 1-3;Barkai, years 4-5) (#15-20) We have built and analyzed theoretical models and used them to predict and analyze the behavior of modules in vivo. We believe that mathematical models are needed to reach a full understanding of biological processes and two theorists have played major roles in the Center for Modular Biology. From 2002 to 2006, Daniel Fisher (Physics, now at Stanford) interacted with a number of groups on different problems, including the generation of segment polarity in Drosophila27, the factors that specify the length of the meiotic spindle (collaboration with. Mitchison), and predicting the speed of evolution (collaboration with A. Murray). Experiments on the distribution and dynamics of microtubules suggest that microtubules are nucleated in a region near the chromosomes, and then transported polewards by a plus-end-directed motor (Eg5) that slides microtubules of opposite polarities past one another28. The model invokes competition between these motors and dynein, a minus-end-directed motor that clusters minus ends. Several predictions of this model have been confirmed by experiments29. We also produced a new theory for the rate of evolution in asexual populations and then performed experiments that confirmed key predictions of the theory and ruled out alternative models, including the extreme form of clonal interference. For the last two years, the PI on this project has been Naama Barkai;who has collaborated on projects examining the mating (project 3, collaboration with A. Murray) and sporulation (new project 6, collaboration with S. Ramanathan) of budding yeast. In mating, theory suggests that cells can decide between two equally attractive partners only if some of the protease that degrades mating pheromones is bound to the cell surface. We have refined this model and verified that successful discrimination requires cell-bound protease. Sporulation shows wide cell-to-cell variation. We have quantified the variable timing through the different steps of sporulation and are using theory and experiment to probe the molecular circuits that control sporulation, and ask how variability might be advantageous in a fluctuating environment. Finally, we have performed experiments to test the hypothesis that the presence of the TATA-box in promoter regions confers both noise and evolvability in gene expression (collaboration with A . Murray).

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Specialized Center (P50)
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Special Emphasis Panel (ZGM1-CBCB-4)
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Harvard University
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Westerman, Erica L; VanKuren, Nicholas W; Massardo, Darli et al. (2018) Aristaless Controls Butterfly Wing Color Variation Used in Mimicry and Mate Choice. Curr Biol 28:3469-3474.e4
Bonham, Kevin S; Wolfe, Benjamin E; Dutton, Rachel J (2017) Extensive horizontal gene transfer in cheese-associated bacteria. Elife 6:
Hormoz, Sahand; Singer, Zakary S; Linton, James M et al. (2016) Inferring Cell-State Transition Dynamics from Lineage Trees and Endpoint Single-Cell Measurements. Cell Syst 3:419-433.e8
Renn, Suzy C P; O'Rourke, Cynthia F; Aubin-Horth, Nadia et al. (2016) Dissecting the Transcriptional Patterns of Social Dominance across Teleosts. Integr Comp Biol 56:1250-1265
Kastman, Erik K; Kamelamela, Noelani; Norville, Josh W et al. (2016) Biotic Interactions Shape the Ecological Distributions of Staphylococcus Species. MBio 7:
Lavrentovich, Maxim O; Wahl, Mary E; Nelson, David R et al. (2016) Spatially Constrained Growth Enhances Conversional Meltdown. Biophys J 110:2800-2808
Battle, Christopher; Broedersz, Chase P; Fakhri, Nikta et al. (2016) Broken detailed balance at mesoscopic scales in active biological systems. Science 352:604-7
Tamari, Zvi; Yona, Avihu H; Pilpel, Yitzhak et al. (2016) Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source. BMC Genomics 17:674
Kim, Wook; Levy, Stuart B; Foster, Kevin R (2016) Rapid radiation in bacteria leads to a division of labour. Nat Commun 7:10508
Muller, Nicolas; Piel, Matthieu; Calvez, Vincent et al. (2016) A Predictive Model for Yeast Cell Polarization in Pheromone Gradients. PLoS Comput Biol 12:e1004795

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