Functional analysis of disease genes causing cerebellar disorders

The cerebellum is a fascinating brain structure. While it has traditionally been regarded solely as a regulator of motor function, recent studies have demonstrated additional roles for the cerebellum in higher-order cognitive functions such as language, emotion, reward, social behaviour and working memory. Accordingly, cerebellar dysfunction is linked to motor diseases such as ataxia, dystonia and tremor, as well as cognitive affective disorders such as autism spectrum disorders and language disorders.

We understand surprisingly little about the molecular processes that underlie the formation of the cerebellum and that, when disrupted, lead to disease. The goal of our research is to provide fundamental insights into the genetic, molecular and cellular mechanisms that govern the development and different diseases of the cerebellum with the  ultimate desire to develop novel treatment options for these disorders.

The project will focus on the functional characterization of novel gene mutations causing cerebellar disorders, with particular emphasis on the effects of disease genes on the dendritic arborisation of developing Purkinje cells in the cerebellum. The approach will be multi-disciplinary and employs a variety of methods including functional experiments in cell lines and primary neurons, as well as modelling of identified patient mutations and their effects using stem cells combined with genome engineering. The project is supervised by two experienced investigators with complementary expertise. Research in the Hammer group at NIH will focus on introducing mutations of interest into primary Purkinje cells and to investigate dendritic phenotypes. Research in the Becker group at Oxford will include further functional analyses in Purkinje cells from mutant mouse models, as well as in human induced pluripotent stem cells.

Becker Group website:
https://www.ndcn.ox.ac.uk/research/cerebellar-disease-group

Hammer Group website:
https://irp.nih.gov/pi/john-hammer