Analysis of cerebellar disease mechanisms using stem
Supervisor: Dr Esther Becker
The cerebellum is the primary center of motor coordination and learning in the central nervous system. Interestingly, this brain structure is also increasingly implicated in higher cognitive functions. Despite our knowledge of the general anatomy and function of the cerebellum, we understand surprisingly little about the molecular processes that govern the formation of this complex brain structure and that, when disrupted, lead to cerebellar disease.
Our lab studies the molecular mechanisms that underlie cerebellar dysfunction in neurological diseases including cerebellar ataxia and autism. The recently developed induced pluripotent stem cell (iPSC) technology offers the exciting possibility to investigate the molecular and cellular disease mechanisms in cerebellar disease using stem cells derived from accessible patient tissues. The main aim of this project will be to establish valuable cell models of ataxia and autism by generating neurons from patient-derived iPSCs. The differentiated neurons will be extensively characterized using a combination of microscopy, electrophysiology and cell biology. Subsequently, the molecular events leading to neuronal dysfunction in these cells will be analysed using a variety of advanced approaches including transcriptomics and proteomics, which can be tailored to the student’s interests. All findings will be validated using post-mortem patient cerebellar tissue and available animal models.
The enthusiastic student will join a stimulating and multidisciplinary research environment. A dedicated studentship for this project is not available and applicants are expected to compete with local studentships or apply for external studentships. Please contact Dr. Esther Becker if you would like to discuss further details about this or related projects and funding possibilities.
Funding: Applicants are expected to compete for local studentships
Contact details: Esther Becker
Applications by: 4th January 2013 https://apply.embark.com/grad/Oxford/16/
Han SS et al. Constructing and deconstructing stem cell models of neurological disease. Neuron 2011, 70:626-44. Cundiff PE and Anderson SA. Impact of induced pluripotent stem cells on the study of central nervous system disease. Curr Opin Genet Dev 2011, 21:354-61. Becker EB et al. Candidate screening of the TRPC3 gene in cerebellar ataxia. Cerebellum 2011, 10:269-9. Becker EB et al, A point mutation in TRPC3 causes abnormal Purkinje cell development and cerebellar ataxia in moonwalker mice. Proc Natl Acad Sci U S A. 2009, 106:6706-11.