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Understanding Cerebellar Development and Disease

Our research focus is the cerebellum. © © Scientific American
Our research focus is the cerebellum.

Welcome to the Becker Group!

We are interested in discovering the genes and biological mechanisms that regulate the development of the cerebellum and in exploring how the impairment of these mechanisms leads to cerebellar diseases.

Research Summary

The cerebellum is known as the primary centre of motor coordination and learning in the central nervous system. In addition, increasing evidence suggests that the "little brain" also contributes to higher cognitive functions including language, emotion and social reward processing. We understand surprisingly little about the molecular processes that underlie the formation of this complex brain structure 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. In particular, we use multi-disciplinary approaches to better understand the disease mechanisms responsible for disorders such as cerebellar ataxia and autism spectrum disorder. Together, our work is helping to provide a more rigorous understanding of the genes and pathways behind these diseases. We hope that our findings will ultimately help to inspire improved clinical treatments.

Cerebellar Ataxia

The cerebellar ataxias are a genetically and clinically diverse group of neurological conditions that primarily affect the cerebellum. A major challenge is to better understand the specific disease-causing mechanisms underlying this complex group of diseases and to identify common pathological pathways that could be targeted therapeutically. One of the emerging key players in cerebellar ataxia is TRPC3, a calcium-permeable ion channel of the transient receptor potential (TRP) family. We have discovered that mutations in the TRPC3 gene cause cerebellar ataxia in the Moonwalker (Mwk) mouse, as well as in human patients. The latter has been designated Spinocerebellar Ataxia type 41 (SCA41). Our ongoing work focuses on the discovery of additional mutations linked to the TRPC3 pathway and their functional and pathological characterisation. Most recently, we have identified the first dominant mutations in the GRM1 gene, encoding the metabotropic glutamate receptor mGluR1, causing Spinocerebellar Ataxia type 44 (SCA44).


Interestingly, the cerebellum has emerged as one of the key brain areas affected in autism spectrum disorder. However, the molecular mechanisms linking cerebellar function to autism remain largely unknown. We are addressing this important question by investigating the role of autism genes in the development and function of the cerebellum by integrating experimental developmental neurobiology and computational analyses.  Our recent work has shown that a subset of autism genes is highly enriched in developing Purkinje cells.

Induced pluripotent stem cells

Our group is one of the few laboratories worldwide who have developed a robust protocol to generate cerebellar neurons from human induced pluripotent stem cells (iPSCs).  This exciting technology allows us, for the first time, to study the development of human cerebellar neurons in the dish using available cells from healthy people as well as patients with ataxia and autism.  We are combining this technology with CRISPR/Cas9 genome engineering to generate unique and isogenic human cerebellar disease models.iPSC_PC_with title.jpg

sources of Funding

  • The Royal Society
  • The Wellcome Trust
  • John Fell OUP Research Fund
  • Rosetrees Trust
  • National Ataxia Foundation
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key publications

Our team

Related research themes