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How Cells Talk to Each Other
and What They Say

Ronojoy Ghosh
Aeronautics and Astronautics
Stanford University
August 2001

I design mathematical models of how biological cells communicate with each other. The goal is to gain insight into these mechanisms and ultimately impact a whole range of biological studies, from cancer research to genetics.

I work on a particular biological process that is ubiquitous in multicellular organisms. This process is called intercellular (and intracellular) communication or signaling. Cells talk to each other incessantly. Most of their vocabulary is unknown and piecing it together is rather like reconstructing "War and Peace" in the original Russian from a few sentences randomly chosen and badly translated into Mongolian. However, by using experimental results from biologists and mathematical modeling, I hope to discover more details about this phenomenon.

One well-known mechanism of communication between cells is varying concentration levels of different proteins on the surface of the cells. By reading off signal protein levels in surrounding cells and producing proteins itself, each cell exchanges information with its immediate neighbors. Intercellular signaling of this type plays an important role during the development of an organism from an embryo to an adult. Among other things, it affects the fate of the cell, i.e., whether it is going to be a nerve or a skin cell, for example. This type of signaling could also result in the cell dying or migrating to another location within the organism.

I have worked so far on modeling a specific group of proteins produced by a cell that determine whether a particular cell on a skin of a frog (Xenopus laevis) is going to have hairs (cilia) or be hairless. An analysis of the model produced at least one very interesting result by varying certain parameters (protein concentration thresholds), researchers could control the entire pattern of hairy and smooth skin cells, at least in mathematical simulation. By adjusting the parameters, all the cells could be ciliated, producing a very hairy frog, or the frog could be completely smooth. This finding could be the basis for a biological experiment in the future.

I am also working on another set of proteins that decide the direction of bristles (hairs) on the wing of a type of fly (Drosphila Melanogaster) during development. Experimental data suggest that at least four proteins are involved in this decision process. Intercellular signaling produces a spatially asymmetric distribution of these proteins within a cell that determines the direction of bristle growth. In this instance, the exact relations between the signaling proteins have not yet been determined experimentally. Our goal is to mathematically model various possible causal relations between the proteins and analyze them. Only the models that replicate observed behavior would be tested experimentally, thereby saving a lot of effort. This system is particularly exciting to study, because biologists think that there are similarities between this signaling mechanism and the one that makes cells cancerous in humans. A deeper understanding of this system might give us insight into the cause and cure of cancer.