The Role of the RasGTPase Superfamily Signaling in C.elegans

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The Ras-family of proteins plays crucial regulatory roles in biology by controlling cell growth and development. Inappropriate activity of this family of proteins is known to lead to human diseases and they play a fundamental role in cell biology. Although we have a good understanding of some simple functions of these proteins, some things we do not know are (i) how they are regulated, (ii) once they are switched on, what other proteins do they bind and (iii) how these proteins are altered to carry out their biological function. We propose to investigate these fundamental issues in cell biology by using C.elegans as a model organism. The "worm" has proven to be very useful for developmental and genetic studies because it is easy to grow, small enough for characterization of every individual cell in the organism (@1000 total cells) and we can manipulate it by safely adding modified genes. Worm genes involved in fundamental cell biological processes are very similar to human genes that have the same cellular function. Therefore, studying worm genes are useful to understanding how human genes work. Our work is focused on the Ras binding protein named BRAP-2. We have determined that mutations in the worm homolog of BRAP-2 cause the animals to show defects in its DNA damage response, which is an important process for maintaining genetic stability and viability of an organism. We plan to carry out further genetic and biochemical studies to better understand how the worm's BRAP-2 regulates the DNA damage rResponse, and discover other genes and proteins BRAP-2 interacts with to fulfill its function.