Pathogenesis of neurodegeneration
The project will investigate the role of transglutaminase 6 in the cerebellum and analyse its link to causing ataxia as an associated pathology.
Cerebellar ataxias are a heterogeneous group of neurodegenerative diseases characterized by progressive imbalance and limb movement deficits. A form of adult onset spinocerebellar ataxia (SCA35) has recently been linked to mutations in the transglutaminase 6 (TG6) gene. Taken together with our demonstration of neuronal expression of TG6 and the presence of autoantibodies to TG6 in immune-mediated ataxia (1,2) this suggests that TG6 plays an important role in neurons involved in motor control and in particular, cerebellar functioning. However, the physiological function of this enzyme remains to be elucidated.
It is crucial to establish the underlying disease causing mechanism(s) as this will identify potential approaches to therapeutic intervention. A combination of structural and cell biological studies are used by our laboratory to determine whether the activity of the multifunctional enzyme is indispensable for neuronal survival or is mis-regulated and ultimately causes neurotoxicity. Within this context, a number of opportunities exist for PhD studies for which we are looking for enthusiastic candidates that are determined to pursue a career in cutting-edge molecular bioscience.
The successful applicant will join an international team of experts with collaborators in specialist clinics and industry, and have access to state-of–the art technology to address these research questions.
More information on the Matrix Biology & Tissue Repair Research Unit.