Management Plan We will implement the following procedures to coordinate the collaborations in this proposal and to monitor the progress of the individual group. Many of these actions are already in existence and have helped to promote the cohesiveness of the research activities at the Center as documented in the reports of our external advisory board, which are attached as Appendix 1. 1. Fellows and their lab members present their work at the weekly group meeting. Each fellow laboratory presents every two months ensuring regular feedback from the group. 2. Andrew Murray meets weekly with one fellow on a rotating basis. This one-on-one discussion ensures consistent and regular mentoring. 3. Each fellow chooses a mentoring committee with advice from Murray and Stern. The committee is composed of three faculty members and meets every year to discuss the fellow's goals, progress, and future research and career plans (committees are listed in Appendix 5). Stern attends each of these meetings, prepares a summary of the committee's observations and recommendations and discusses possible actions with the fellow. 4. We will assemble an External Advisory Board to provide guidance on the success of the fellows program and the performance of the NIGMS funded projects. We will also seek guidance from the Board on our outreach and education efforts and on the goal to coordinate Systems Biology activities with the Department of Systems Biology at the Medical School. We had an excellent experience with the External Advisory Board chosen to supervise our first Center grant period. The board's outside perspective provided critical feedback on the progress of the research projects, the trajectory of individual fellows, and the fellows program in general. 5. The non-Harvard project leaders (Elowitz and Barkai) have committed to spend at least a week per year at the FAS Center for Systems Biology. Even such short periods have proven effective in the past in creating a special connection between Barkai and Elowitz on the one hand and Center researchers on the other. Barkai and Elowitz have invigorated many research projects at the Center with their insightful advice. Over the last 2 months, Barkai has spent a 9 month sabbatical and made a 1 month summer visit to the Center, and we are enthusiastic about repeating the latter on an annual basis. 6. Center website: we have created a CMB website which includes a description of projects and participating scientists, CMB publications and oversight. Most importantly, the website provides free access to all resources created by CMB projects (see below in progress report). We will upgrade the website to include the new projects, people and resources from this proposal. In addition, we will add a new feature describing and advertising the joint activities of the Boston-wide systems biology initiative CSB2 (see below), and joint activities with other NIGMS funded National Centers for Systems Biology. 7. We will continue to hold regular meetings of all the Harvard Pis associated with the grant. These will occur monthly and will be supplemented by two otheractivities: a weekly Friday afternoon talk given by a member of the Harvard systems biology community, which is hosted by the FAS Center for Systems Biology, and a monthly student/faculty talk hosted by the Harvard-wide Systems Biology graduate program. All the Harvardbased Pis will attend these talks. 8. We will organize an annual 2-3 day retreat for all researchers on the grant. We will invite the Harvard Systems Biology community plus interested faculty from Harvard and Boston area Systems Biology Centers as part of the Council on Systems Biology in Boston initiative (see below). The format of past retreats - each speaker introduces a project in need of input/collaboration from another discipline - was well received and helped to create new connections between researchers from different backgrounds. We will therefore build on this successful format.

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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Wahl, Mary E; Murray, Andrew W (2016) Multicellularity makes somatic differentiation evolutionarily stable. Proc Natl Acad Sci U S A 113:8362-7
Kastman, Erik K; Kamelamela, Noelani; Norville, Josh W et al. (2016) Biotic Interactions Shape the Ecological Distributions of Staphylococcus Species. MBio 7:
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
Lavrentovich, Maxim O; Wahl, Mary E; Nelson, David R et al. (2016) Spatially Constrained Growth Enhances Conversional Meltdown. Biophys J 110:2800-8
Battle, Christopher; Broedersz, Chase P; Fakhri, Nikta et al. (2016) Broken detailed balance at mesoscopic scales in active biological systems. Science 352:604-7
Kim, Wook; Levy, Stuart B; Foster, Kevin R (2016) Rapid radiation in bacteria leads to a division of labour. Nat Commun 7:10508
Tamari, Zvi; Yona, Avihu H; Pilpel, Yitzhak et al. (2016) Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source. BMC Genomics 17:674
Muller, Nicolas; Piel, Matthieu; Calvez, Vincent et al. (2016) A Predictive Model for Yeast Cell Polarization in Pheromone Gradients. PLoS Comput Biol 12:e1004795
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
Möbius, Wolfram; Murray, Andrew W; Nelson, David R (2015) How Obstacles Perturb Population Fronts and Alter Their Genetic Structure. PLoS Comput Biol 11:e1004615

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