Targeted Protein Degradation: From Small Molecules to Complex Organelles

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ABSTRACT Support is requested for a Keystone Symposia conference entitled Targeted Protein Degradation: From Small Molecules to Complex Organelles, organized by Drs. Sascha Martens, Tim Clausen and Judith Frydman. The conference will be held in Vienna, Austria from June 6-9, 2021. Targeted protein degradation plays a critical role in regulating nearly all cellular functions, and as such, its dysfunction is associated with severe pathologies including diseases like cancer, neurodegeneration and age- associated diseases. Therefore, fundamental insights into protein clearance pathways might be harnessed for therapeutic applications against a wide range of diseases. While much progress has been made in revealing mechanisms of autophagy and the ubiquitin-proteasome system, the major protein degradation pathways defined thus far, these fields continue to remain isolated from each other despite the interconnection of these processes. This separation is now leading to an urgent need to discuss the interplay of these pathways at the molecular and cellular levels to integrate our understanding of these processes and how they contribute to disease pathology. This conference will bring together researchers from these different fields, who do not typically interact, to build a holistic and integrated vision of protein degradation. Such an integrative conference highlighting the connections between the different branches of protein degradation research does not yet exist, so this Keystone Symposia conference will be the first of its kind to reshape how these fields interact and collaborate to yield transformative insights into both basic science and disease processes. Topics of discussion will include: (1) Substrate recognition and processing by energy-dependent proteases, autophagy and lysosomal pathways; (2) Signals targeting proteins to distinct degradation pathways; (3) Interplay between proteolytic systems and chaperone pathways; (4) Reprogramming degradation with small molecules for therapeutic applications; (5) Degradation programs driving global proteome remodeling. Attendees will be exposed to novel perspectives, as well as methods, techniques and approaches, that will advance research within their field, and across the many different components in the protein degradation landscape.