YIP DISSECTING THE PHYSICAL PRINCIPLES THAT CONTROL THE SPATIAL ORGANIZATION OF INTRACELLULAR SIGNALING
Abstract
The plasma membrane of mammalian cells serves as a complex signaling platform where hundreds of molecular receptors sense information in the extracellular space and initiate cellular changes in response to these signals. These receptors are not randomly distributed, but rather many receptors are locally concentrated with specific cytosolic signaling molecules within micron sized signaling clusters on the plasma membrane. Signaling clusters can be found in all cell types including neurons and immune cells, and the formation of signaling clusters is required for many intracellular signaling processes. The goal of our proposed research is to understand (1) the physical principles that drive self-organization into signaling clusters at the plasma membrane and (2) how organization into signaling clusters triggers intracellular signaling. Our unique approach is to reverse-engineer signaling pathways from purified components and use fluorescence microscopy to visualize signaling in these engineered systems. We will experimentally dissect the physical principles responsible for self-organization into clusters and measure how molecular organization controls downstream activity. We will also use computational modeling to describe and understand the emergent behaviors of the reconstituted signaling clusters. Controlling the spatial organization of signaling molecules is a viable yet underexplored strategy to manipulate intracellular signaling pathways. The proposed research will provide a detailed understanding of the physical principles that underly the organization of signaling clusters. This knowledge will help in the development of perturbations to change signaling. Signaling clusters can be found in all cell types, and the general principles we uncover could likely be applied to any specific cell type of interest.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 07, 2023
- Source ID
- FA95502210207
Entities
People
- Lindsay B Case
Organizations
- Air Force Office of Scientific Research
- Massachusetts Institute of Technology
- United States Air Force