Dr Greg Findlay and Professor Satpal Virdee, Principal Investigators in the MRC Protein Phosphorylation and Ubiquitylation Unit, have been awarded Wellcome Discovery Awards. The 8-year funding that totals ~£4.2M will support their research in Intellectual Disability and E3 ligase enzymes, respectively.

This new scheme from the Wellcome Trust ‘provides funding for established researchers and teams from any discipline who want to pursue bold and creative research ideas to deliver significant shifts in understanding that could improve human life, health and wellbeing’.

Greg Findlay

“Intellectual disability is a major mental health problem that affects 1-3% of the world population, which is frequently caused by genetic mutations that disrupt cell communication. In our research programme, we will develop and deploy cutting-edge biochemical approaches in stem cell models of human nervous system development, to understand how defective cell communication causes intellectual disability. This will identify new therapeutic targets, which we hope will eventually lead to treatments for these debilitating conditions,” explained Greg. “This research stems from previous work published by our group in Cell Reports, Developmental Cell and Science Signalling.”

Bustos et al (2018) Cell Reports doi: 10.1016/j.celrep.2018.04.022

Bustos et al (2018) Developmental Cell doi: 10.1016/j.devcel.2020.09.025

Segarra-Fas et al (2022) Science Signalling doi: 10.1126/scisignal.abm5995

Greg was awarded ~£1.9M which will support 3 full-time positions. He will collaborate with researchers from the University of Dundee, University of Glasgow, MRC Mary Lyon Centre at Harwell, Oxford and University of Exeter.

Satpal Virdee

“E3 ligase enzymes regulate virtually all aspects of the cell and their overactivity, or lack thereof, underlies diseases including cancer, neurodegeneration and autoimmunity. E3 enzymes are also central to a promising new class of medicines known as degraders. This Wellcome Discovery will uncover and characterize novel members of this important enzyme family with a view to unlocking new fundamental biology and strategies for treating disease. Technology will also be developed that will facilitate the study of E3 enzymes and the development of medicines that modulate their activity,” explained Satpal. “This work will build upon previous research published by us in Nature Chemical Biology, Cell Chemical Biology and Nature”.

Mabbitt et al. (2020) Nat Chem Biol.. doi: 10.1038/s41589-020-0598-6

Mathur et al. (2020) Cell Chem Biol. doi: 10.1016/j.chembiol.2019.11.013

Pao et al. (2018) Nature, doi:10.1038/s41586-018-0026-1

“E3 ligase enzymes are central to cellular homeostasis and when they go awry this can lead to disease. The biological discoveries and the technology developed with this proposal will shed light on the intricate mechanisms of action and cellular function of E3 enzymes. In turn, this will present new strategies for the creation of new medicines.”

Satpal was awarded ~£2.3M which will support 4 full-time positions and will collaborate with researchers from Institute of Molecular Pathology (Austria).

Dario Alessi, Director of the MRC PPU states “I congratulate Greg and Satpal in securing these prestigious awards that will enable them to develop their research programs, tackle fundamental questions, and develop technology that has strong potential to help with understanding and developing improved diagnosis and treatment for debilitating human diseases."