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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. Moreover, this "little brain" is also increasingly implicated in higher cognitive functions including language, emotion and executive function. 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. 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 recently discovered that mutations in the TRPC3 cause cerebellar ataxia in the Moonwalker (Mwk) mouse, as well as in human patients. The latter has been designated Spinocerebellar Ataxia type 41 (SCA41). Moreover, TRPC3 is a key player in a pathway that is linked to several other forms of cerebellar ataxia, thus making this channel an attractive target for pharmacological modulation and potential therapies. Our ongoing work focuses on the discovery of additional mutations linked to the TRPC3 pathway and their functional and pathological characterisation.

Interestingly, the Mwk TRPC3 mutation does not only lead to neurodegeneration but also causes impairments during cerebellar development. Our recent studies are beginning to reveal the principal molecular mechanisms including aberrant lipid metabolism that link activated TRPC3 signaling to abnormal Purkinje cell development and cerebellar ataxia.


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.

Induced pluripotent stem cells

One of our research aims is the generation and characterisation of cerebellar neurons derived from human induced pluripotent stem cells (iPSCs).  This exciting technology will allow 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.

sources of Funding

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

Our team

  • Esther Becker
    Esther Becker

    Associate Professor of Neurobiology

  • Friederike Winter

    Postgraduate Student

  • Maggie Wong

    Postgraduate Student

  • Lauren Watson
    Lauren Watson

    Postdoctoral Research Scientist

  • Liam Argent

    Postgraduate Student

Reaching out to the public

  • MRC FGU Public engagement

    Find out more about the Becker Group and the Functional Genomics Unit's public engagement here.

  • Empowered Women

    Esther was one of the invited keynote speakers at the "Empowered Women" event in April 2014 that was hosted by the Charity Wishful Smiles together with Barry Gardiner MP at the Houses of Parliament.

Related research themes