Grant: Operating Grant

Most biological functions are performed by proteins, and most proteins fold up into regular three dimensional structures that determine their biological function. However, a large subset of proteins, including many associated with important diseases (such as p53, BRCA1 and CFTR) are not totally folded. They contain so-called "disordered" regions which do not take on a specific structure and do not perform enzymatic functions. The function of most of these disordered regions is not understood, but one model (that has been established in some cases) is that they contain short segments that are important for determining when and where the protein is active. This project will systematically search for the segments within the disordered regions that are likely to be important based on their patterns of evolution. Then we will confirm that the segments we identify actually control the activity of the proteins in which they are found by doing a series of experiments in yeast (a simple model organism). If our hypothesis is right, we will be able to better understand the function of the disordered regions. This will be an important step towards predicting how proteins are turned on and off, both in normal cells and when disease-causing mutations occur.