Modeling Biological Networks

IV.1 Coordinators
IV.2 Participants
IV.3 Introduction
IV.4 Background and Significance
IV.5 Research Plan
IV.6 Specific Subprojects

• IV.6.ii Subproject 2 Topology of Signaling Protein Networks and the Cytoskeleton
  • IV.6.ii.a Datasources
  • IV.6.ii.b Overview
  • IV.6.ii.c Hypotheses
  • IV.6.ii.d Specific Aims
  • IV.6.ii.e Preliminary Results and Research Plan
    • IV.6.ii.e.1 Aim 1
    • IV.6.ii.e.2 Aim 2
    • IV.6.ii.e.3 Aim 3
    • IV.6.ii.e.4 Aim 4
• [ Other Subprojects ]

IV.7 Connection to Specific Projects 2 (cytoskeleton) and 3 (organogenesis)
IV.8 Timeline

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IV.6.ii.c Hypotheses:

A cell requires constant interaction with its environment for normal function. Membrane-bound receptors continuously receive signals from neighboring cells or the extracellular matrix. A change in their state, due to either biochemical or physical modifications, typically leads to a cascade of signaling events which may involve further chemical changes (e.g. phosphorylation) or physical processes (e.g. diffusion). We still know very little about signal transmission from the cell surface to a particular cellular compartment in vivo. Most maps of biochemical signaling pathways are partial, with identified beginning and end points, question marks representing unknown intermediary components and arrows symbolizing putative trajectories of molecular movement. Numerous signaling molecules must arrange reversibly and precisely to carry information (Isenberg, 1996). How do these molecules find each other and react in the correct sequence?

We hypothesize that intracellular signaling relies on the structure of the cytoskeleton. The interconnected cytoskeletal filaments provide a natural means of communication between the distant parts of the cell, in particular the cell membrane and the nucleus. Numerous proteins with diverse functions transiently or irreversibly bind to the cytoskeleton (Mochly-Rosen, 1995; Janmey, 1998; Schmidt et al., 1998). If the cytoskeleton indeed participates in signaling then signaling molecules must strongly correlate with cytoskeletal molecules. The analysis of large-scale protein networks allows us to study such correlations.

IV.6.ii.d Specific Aims:
1. To quantitatively characterize the correlation between cytoskeletal and signaling proteins.
2. To demonstrate the preferential correlation between cytoskeletal and signaling proteins.
3. To gain insight on the spatial structure and organization of signaling pathways.
4. To analyze how general our results are across different organisms.