Project 171279

Cancer is a disease where the normal controls regulating cell division are no longer active. Cells are controlled by their genes, and one class, termed tumour suppressors, encode 'do not divide' signals. When these are inhibited, excess cell division occurs which manifests as a tumour. Another important feature in multi-cell animals are the signal that tell cells to stick together. A progression to cell metastasis occurs when the signals for "cells stick together" and cell "do not divide" are mis-regulated. Our proposal focuses on the tumour suppressor Merlin. Loss of Merlin activity leads to tumours within the brain and spinal cord. How Merlin tells cells "do not divide" is not understood. We are using the long history of Drosophila genetics to identify proteins that interact with Merlin to help Merlin carry out its tumour suppressor functions. We have identified and will further characterize several proteins called Moesin, Sip1 and Slik. Moesin is required to control signal to tell cells to stick together Sip1 is a scaffold protein that interacts with Merlin and Moesin to control cell growth and to keep cells "sticking together" We propose that Merlin is part of a large complex of proteins that help Merlin control how cells grow and when to stick together. Our ultimate goal is to understand how Merlin acts as a tumour suppressor to aid in diagnosis and therapy of Neurofibromatosis Type 2 tumours.

using Drosophila genetics to identify and characterize protein partners of the Merlin tumour suppressor