Abstract

Grzegorz Kudla is a Professor at the MRC Human Genetics Unit in Edinburgh, where his group develops methods to measure the functional impact of genetic variants at scale. Using multiplex assays of variant effects (MAVEs), they map how mutations alter enzymatic activity, protein stability, and cell signalling in genes linked to rare and common diseases. Most recently, they have focused on Parkinson’s risk genes GBA1 and Parkin, using mechanistic assays to reveal structural defects that alter enzyme function and drive pathogenicity. In parallel, the lab investigates how synonymous mutations disrupt gene expression through unexpected effects on splicing and translation. By combining high-throughput mutagenesis with biochemical assays and RNA analysis, Kudla’s work aims to decode how genotype shapes molecular phenotype and to develop tools for interpreting variants of uncertain significance. He trained with Maciej Zylicz (Warsaw), Joshua Plotkin (Harvard) and David Tollervey (Edinburgh), and co-developed RNA methods including CRAC , CLASH, and COMRADES .