Combining pharmacology & AI to identify novel targets controlling proteostasis in neuronal cells

Lead Research Organisation: Queen Mary, University of London
Department Name: William Harvey Research Institute

Abstract

Neurodegenerative diseases (NDs) are debilitating conditions linked with aberrant health aging, a
key BBSRC focus. Whilst the molecular origins for NDs are multiple, the dysregulation of protein
homeostasis -or proteostasis- network, involving protein synthesis, folding & trafficking, is central
to the progression of NDs. This results in cellular stresses leading to cell death. At the molecular
level, it is assumed that the accumulation of pathological aggregates result from non-physiological
aggregation of proteins prone to misfolding, accumulating due to age-related deficits in proteostatic
systems, including the proteasome, mitochondrial dysfunction, stress & autophagic system.
Our hypothesis is that although each ND involves distinct culprit proteins; common
regulatory nodes exist driving changes in protein homeostasis. Our aim is to use previously
developed iPS cell models of NDs to identify targets for modulating proteostasis in neuronal
cells. We will achieve this by harnessing Sosei-Heptares' in house AI & drug discovery
platform coupled with well defined in house proprietary compounds.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/T008709/1 30/09/2020 29/09/2028
2725951 Studentship BB/T008709/1 25/09/2022 29/09/2026 Ambegoda Amarasinghe Perera