Join the Duke Center for Quantitative Biodesign on Friday, October 4, 2024 at 3:00 pm in Wilkinson 021. Our guest speaker, Dr. Alex Holehouse, is an Assistant Professor of Biochemistry and Molecular Biophysics at Washington University in St. Louis School of Medicine, where he will be discussing “Mapping from sequence to function in intrinsically disordered regions.”
The Holehouse Lab studies how biological function is encoded into intrinsically disordered proteins and how this goes wrong in disease. They use a combination of physics-based models, bioinformatics, deep learning, and quantitative cell biology.
Bio: Alex received his Ph.D. Washington University in St. Louis, Computational Biophysics in 2017, MsC. From Imperial College London, Computer Science in 2011, and his MBioch from University of Oxford, Molecular & Cellular Biochemistry in 2010.
Abstract:Intrinsically disordered protein regions (IDRs) are ubiquitous across all life kingdoms and play various essential cellular roles. Unlike folded domains, which are well-described by one or a small number of structurally similar states, IDRs exist in a collection of structurally distinct conformers known as an ensemble. While IDRs are ‘disordered’, they are not ‘unstructured’ – sequence-specific effects influence intra- and inter-molecular interactions that ultimately dictate biological function. Here, we will discuss recent advances that combine chemical physics, informatics, and deep learning to infer biologically important functions directly from sequence. These approaches offer opportunities for understanding IDR evolution, interpretation of disease-associated variants of unknown significance, and rationally designing functional IDRs with specific functional properties.
