The 2016 IDP GRC entitled, Disordered Proteins: From Mechanisms to Therapeutic Opportunities, to be held June 26-July 1, 2016, in Les Diablerets, Switzerland, will address emerging themes regarding the biological roles of disordered proteins in both normal and diseased cells. Importantly, disordered proteins are involved in numerous human diseases [e.g., cancer, neurodegenerative diseases, and infectious diseases (e.g., viral infections)]; therefore, the conference will address many disease-related topics. Disordered proteins, or protein regions, constitute ~50% of the human proteome but biological functions and molecular mechanisms of these are poorly understood. While structure/function studies of folded proteins are paradigmic, disordered proteins have been recognized as a branch of structural biology for only ~10 years. Consequently, our understanding of disorder/function relationships is grossly incomplete. Investigating heterogeneous conformations of disordered proteins is still a bottleneck for structural studies and requires further development of specialized methods and conceptual frameworks. A major challenge is to determine the molecular mechanisms of disordered protein function to establish relationships between disorder and function. Consequently, structural investigations must be coupled with analysis of function. Disordered proteins are linked with many different human diseases; therefore, detailed studies into disorder-function relationships will reveal disease mechanisms. An emerging frontier in the field is the concept of drugging IDPs. Recent publications report small molecules that act by modulating the dynamic features of disordered/flexible regions of proteins and show promise as cancer and diabetes therapeutics. This is an emerging branch of disordered proteins research. Finally, also exciting is the realization that disordered segments within proteins can confer the ability to assemble into liquid-like droplets via phase separation. This phenomenon gives rise to various membrane-less organelles within cells. The first papers within this emerging field have been published since 2012 and many other investigators are now jumping into this new branch of the structural biology field. Key objectives for the conference are as follows: Objective 1. To present lectures on the molecular mechanisms of IDP function; Objective 2. To present lectures on therapeutic opportunities involving disordered proteins; Objective 3. To present lectures on the role of disordered proteins in membrane-less organelles and other supra-molecular assemblages. We have also identified the following key organizational objective for the conference: Objective 4. To promote the involvement of women and/or underrepresented minorities who are US citizens or permanent residents in studies of disordered proteins.
Disordered proteins are involved in the mechanisms of numerous diseases, including cancer, neurodegenerative diseases, and infectious diseases (e.g., viral infections). Furthermore, important discoveries have recently been made showing that small molecules can alter cellular behavior through interactions with disordered and/or flexible proteins, ushering in a new era in drug discovery. The 2016 Intrinsically Disordered Proteins (IDPs) Gordon Research Conference (GRC) will place emphasis on, i) the molecular mechanisms of disordered protein function, with focus on how these mechanisms are altered in disease, and ii) therapeutics that target disordered proteins and/or their interaction partners, and, therefore, will be highly relevant to human health.
