Greg Findlay and Francisco Bustos awarded Tenovus Scotland Research Grant

Francisco Bustos and Greg Findlay
Francisco Bustos and Greg Findlay

Greg Findlay and Francisco Bustos, a postdoctoral researcher in Greg’s group, were recently awarded a £20,000 Tenovus Scotland Research Grant to engineer an RNF12 E3 ligase substrate degrader as a therapeutic strategy in Tonne-Kalscheuer Syndrome (TOKAS) intellectual disability.

Development of effective treatments for intellectual disability syndromes is an urgent challenge for biomedicine. TOKAS is a neurodevelopmental disorder caused by mutations in the RNF12/RLIM gene, which disrupt the E3 ubiquitin ligase activity of its gene product, RNF12. This results in defective RNF12 activity and accumulation of its substrate REX1, causing abnormal differentiation of neuronal cells that likely underpins TOKAS aetiology.

The generous award of this grant will allow Francisco and Greg, in collaboration with Gopal Sapkota from the MRC-PPU and Alejandro Rojas-Fernandez (UACH, Chile), to engineer an Affinity-directed Protein Missile (AdPROM) to specifically restore REX1 ubiquitylation in order to normalise REX1 expression in TOKAS mutant cells. This approach for selective destruction of a key RNF12 substrate will be a significant initial step towards development of treatments for TOKAS and other ubiquitin-system-related intellectual disabilities.

Grant: Tenovus Scotland Research Grant Application T19-25

‘Engineering an RNF12 E3 ligase substrate degrader as a therapeutic strategy in Tonne-Kalscheuer Syndrome (TOKAS) intellectual disability’

Principal Investigator

Lab Member