NIH P50

Center for Biological Systems Architecture (CBSA)

Christina D. Smolke (PI)
Anand Asthagiri      David Baltimore      John Doyle      Michael Elowitz
Grant Jensen      Richard Murray      Dianne Newman      Rob Phillips

Goals Experimental and theoretical tools for understanding the regulatory architecture of cells and multi-cellular systems Education of the next generation of systems biologists Application of new tools to driving applications Objectives CDS: A modular platform for detecting activation through signalling pathways using FRED-basted molecular sensors applied to mapK signalling pathways.

Timeline 24 Oct, 3 pm: objectives + writing assignments 30 Oct-2 Nov: work on individual sections 3 Nov (Fri): first cut at individual sections due 5 Nov (Sun): first draft of full proposal out 6-10 Nov: updates to individual sections 13 Nov (Mon): second cut at individual sections due 14-15 Nov: CDS writing 16-19 Nov: Grants.gov massaging 20-21 Nov: polishing

Proposal Outline

Program summary (2 pages)

• Statement of goals and objectives (milestones)
• Build off of vision statement
• What makes us unique? Bringing together three essential elements
  • Computational and theoretical infrastucture for pursuing regulatory architectures
  • Unique experimental platforms
  • Unique combination of driving biological problems
• Move from small scale static to large scale, dynamic
  • Look across a class of biological applications
  • Make use of theory and computational tools to guide experiments
  • Spatial structure and stochastics become important (primarily affect the dynamics of regulation)

Organizational structure/decision making plan (2 pages)

Christina Smolke (PI)
Thrust I: Theory and computation JD? Model-checking and SOS methods for analysis of regulatory networks (John) Stochastic simulation/SBML with spatial structure (John, CACR) Feedback design of synthetic regulatory structures (Richard, John)	Thrust II: Experimental Platforms RP? FRET-based molecular sensors (Christina) Cryo-EM (Grant) Single-cell measurements (Rob, Michael, Christina)	Thrust III: Driving Biological Problems DB? NFkB, G-protein, MAPK signal transduction [& inflammation?] (David, Anand) Multi-component phosphorelays in bacterial fate choice and development (Michael) Regulatory architectures in biofilms (Dianne) Regulatory architectures in bacterial envelopes and structures (Grant, Rob, ???) Re-engineering core microbial processes/metabolic engineering (Christina)
Postdoc program Seed funding? Visitors Workshops?

Timeline (2 pages)

• List of milestones for years 1, 2, 3 and 4-5