Transcending Scales of Protein Disorder from Molecules to Medicines

This GRC focuses on providing a broad overview of the field of intrinsically disordered proteins (IDPs). IDPs have emerged as a major class of proteins that are involved in diverse cellular processes ranging from stress response to the regulation of organelle assembly, RNA availability, and transcription. IDPs have also been implicated in diseases spanning cancer, neurodegenerative disorders and viral infection. In spite of ubiquitous nature of IDPs, a general understanding of the evolution and underlying functional mechanisms of IDPs remains poorly understood in all but a few systems.

Thus, the overarching goal of this meeting is to bring together scientists from diverse fields with the focus of developing a comprehensive and synoptic understanding of how IDPs can facilitate such a wide range of functions, and how dysfunction of these proteins is associated with disease.

The key objectives of this conference are:

• To elucidate the range of molecular mechanisms of IDP function. The hallmark feature of IDPs is that the functional state is an ensemble of often very different structural states. This poses unique challenges for experimentally investigating IDPs. Many lectures will focus on experimental characterization of IDPs in order to uncover the molecular mechanisms of function and disease etiology.
• To investigate the role of IDPs in the function of membrane-less organelles. Membrane-less organelles have various components, often containing RNA, and often being regulated through post-translational modifications. Several lectures will focus on phase transitions in IDPs, how they can be regulated, and their relationship to the properties of membrane-less organelles, and where relevant how these are related to disease.
• To elucidate the complex structure-function relationships in IDPs and their evolution. Because IDPs have high sequence variability, identifying the sequence determinants of functional changes has been challenging, as has been determining the evolution of new functions. Several presentations will address the emergent properties of IDPs and their evolution.

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.