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SUMMARY:The RSC Jeremy Knowles Award Lecture - Adapting the Chemistry and/
 or Biology of Proteostasis to Ameliorate Protein Aggregation Diseases  - J
 effery W. Kelly\, Departments of Chemistry and Molecular Medicine\, and Th
 e Skaggs Institute of Chemical Biology\, The Scripps Research Institute\, 
 10550 North Torrey Pines Rd.\, La Jolla\, CA 92037
DTSTART:20180223T163000Z
DTEND:20180223T173000Z
UID:TALK101536@talks.cam.ac.uk
CONTACT:Priyanka Joshi
DESCRIPTION:The cellular protein homeostasis\, or proteostasis network\, r
 egulates proteome function by controlling ribosomal protein synthesis\, ch
 aperone and chaperonin mediated protein folding\, protein trafficking\, pr
 otein degradation and related processes. Stress responsive signaling pathw
 ays match proteostasis network capacity with demand in each subcellular co
 mpartment to maintain or alter cellular homeostasis. The beginning of the 
 seminar will focus on how the proteostasis network can be adapted pharmaco
 logically through stress responsive signaling to alleviate the gain-of-tox
 ic-function diseases\, including light chain amyloidosis and the transthyr
 etin amyloidosis\, where excessive secretion of misfolding and aggregation
  of proteins leads to a degenerative phenotypes. We will also cover our ef
 forts towards the discovery of autophagy activators for ameliorating the T
 auopathies. These drug candidates are envisioned to be generally useful fo
 r ameliorating multiple neurodegenerative diseases based on human genetic 
 evidence. These  strategies will be contrasted with high affinity small mo
 lecule binding to the normally folded structural ensemble of an aggregatio
 n-prone protein inside and/or outside of the cell to stabilize the native 
 state\, lowering the population of misfolded\, misassembly competent state
 s that lead to aggregates\, including amyloid fibrils. Our progress toward
 s discovering light chain and transthyretin kinetic stabilizers will be co
 vered. \n
LOCATION:Wolfson Lecture Theatre\, Department of Chemistry
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