Understanding Cerebellar Development and Disease
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.
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.
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
Join the lab
We are a young and enthusiastic group. Enquiries from motivated and talented students and post-docs to discuss available research projects and funding possibilities are always welcome. Get in touch
Opportunities for DPhil/PhD projects in the Becker group are available through a number of graduate programmes:
- Wellcome Trust Doctoral Programme in Neuroscience
- OXION Programme
- Interdisciplinary Bioscience Doctoral Training Partnership
Nov 2016: MSc student Alexandra Soca joins us from Nijmegen - Welcome!
Oct 2016: Liam passed his transfer viva - Congratulations!
Oct 2016: Congratulations to Lauren, who has been awarded a prestigious Fulford Junior Research Fellowship from Somerville College!
June 2016: Maggie has been accepted into the Young Investigator Training Programme at FENS 2016 - Congratulations!
April 2016: MSc Neuroscience student Libby Bamber joins the lab - Welcome!
Dec 2015: MSc student Danique Beijer from Nijmegen joins the lab - Welcome!
Nov 2015: Maggie passed her transfer viva - Congratulations!
Oct 2015: Welcome to our new DPhil student Liam Argent!
May 2015: Congratulations! Our poster "From mice to men: TRPC3 in cerebellar ataxia" won the "best poster" award at the Oxford Rare Disease Initiative Conference
Jan 2015: Welcome to post-doctoral fellow Lauren Watson!
Reaching out to the public
Find out more about the Becker Group and the Functional Genomics Unit's public engagement here.
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.