Grant: Operating Grant

Proteins are major macromolecules of the cell that have incredibly versatile functions. Some are enzymes, others transport molecules inside the cell or in the bloodstream, yet others make sure our immune system stays alert. But to be able do so, each protein needs to adopt its unique shape that determines its function. Starting as a linear chain, proteins fold into intricate shapes like cellular origami. But when this process goes awry, the result can be a disease like Alzheimer's disease, Parkinson's disease or even cancer. Because protein folding is such a fundamental process for all living organisms, cells have evolved special machines (themselves also proteins) whose function is to make sure proteins fold correctly. These proteins are aptly called chaperones. In this project, we will study how these chaperones can associate with thousands of diverse proteins but, at the same time, provide unique support to each of them. In particular, we will characterize how so-called co-chaperones, which constantly regulate the function of chaperones, provide specificity to the chaperone machinery inside the cell. We will systematically identify the proteins that each co-chaperone associates with, and use this knowledge to understand how drugs in clinical use affect these associations. The results from this study will help researchers to understand the chaperone/co-cochaperone network in unprecedented detail, biotechnology and pharmaceutical companies to understand how their drugs affect cells, and, ultimately, patients to benefit from more specific and more potent drugs against diverse diseases.