Disordered Proteins: From Mechanisms to Therapeutic Opportunities

This GRC will provide a broad overview of the intrinsically disordered proteins (IDP) field and also address the state-of-the-art in several vital, emerging areas. Cutting-edge themes regarding the roles of disordered proteins in both normal cells and disease will be discussed. Disordered proteins are involved in the pathology of numerous diseases, including cancer, neurodegenerative diseases, and infectious diseases (e.g., viral infections) and important discoveries have recently shown that small molecules can alter cellular behavior through interactions with disordered regions of proteins. Owing to the importance of these results in drug discovery, many lectures will address therapeutics- and disease-related themes.

The key scientific objectives of this conference are:

• To address the molecular mechanisms of IDP function. While it is widely appreciated that a large fraction of human proteins exhibit disordered regions, in only a small fraction of cases are the mechanisms of their functions understood. Many lectures will endeavor to fill this knowledge gap. The conference will also address how the molecular mechanisms of disordered protein function are altered in disease.
• To discuss therapeutic opportunities involving disordered proteins. While the concept of "drugging IDPs" was once considered heretical, there are now several published reports on small molecules that exert their biological effects through interactions with disordered and/or flexible regions of proteins. Several lectures will address innovative therapeutic approaches for targeting disordered proteins and/or their interaction partners, with speakers representing academic research groups as well as major pharmaceutical companies.
• To address the role of disordered proteins in membrane-less organelles. Recent discoveries have shown that certain disordered proteins, either individually or together with RNA, weakly self-associate to cause phase separation into liquid-like or gel-like structures within membrane-less organelles. Little is known, however, about the molecular mechanisms of these assembly phenomena and how these assemblies contribute to biological functions. Furthermore, membrane-less organelles have been implicated in disease but the underlying molecular mechanisms are poorly understood. Several pioneers in this emerging field will present lectures at the conference.

We encourage participation in the conference by scientists already working in the disordered proteins field, cell biologists working on IDP-related molecular processes, and pharmacologists seeking new targets but also welcome others less familiar with the pervasive roles of IDPs in biology and disease. We especially encourage young scientists to attend this GRC, and the accompanying GRS, to learn about the scientific challenges and opportunities that await them.