MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

Understanding dominant mutations that cause misassembly of cytoskeletal proteins: from patient genetics to cellular mechanisms

Dr Joe Marsh

Marsh research 2

Secondary Supervisors: Julie Welburn (WTCCB), Ann Wheeler 

Mutations of cytoskeletal proteins are associated with a variety of human disorders. However, the mechanisms underlying pathogenesis can be profoundly different than for other proteins: they often show dominant inheritance related to the misassembly of mutant proteins into cytoskeletal filaments or molecular motors. In this project, the student will first use computational analyses to identify pathogenic mutations and prioritise mutations incorrectly predicted by current approaches. Next, they will investigate the molecular mechanisms of disease using cell biology, single molecule reconstitution and structural biology as suitable. Finally, they will use machine learning to develop new models for predicting pathogenic mutations.