This studentship is focused on understanding the molecular basis of neurodegeneration through the study of molecular motors, with the aim of opening up new avenues for intervention in disease. You will be part of a multidisciplinary collaboration between the Twelvetrees lab in the Sheffield Institute for Translational Neuroscience (SITraN) and the Craggs lab in the Department of Chemistry at the University of Sheffield.
Neurons form complex extended cellular structures. For example, motor neurons have cell bodies in the spinal cord, but extend axons down to the muscles of the hands and feet. This length presents a problem for neurons, as most of their newly synthesized protein is made in the cell body and then transported long distances down the axon to its site of use. Consequently, defects in transport are observed in many neurodegenerative conditions, including Alzheimer’s, Parkinson’s, Huntington’s and ALS, and understanding the mechanism of axonal transport is crucial to providing new avenues for therapeutic intervention. Polarised long-range transport along the microtubules in neuronal axons is powered by kinesin motors. The goal of this project is to understand how disease-causing mutations in kinesin disrupt its structure and ability to transport axonal cargo.
This project represents a truly unique opportunity to integrate neuronal models of disease with biochemical & biophysical approaches, exploring the molecular basis of transport by kinesin across systems and scales. The research groups linked to this project encompass expertise in the structural, biophysical and neuronal cell biology of kinesin mediated axonal transport.
You will be trained in advanced real-time imaging and analysis (single molecule FRET; single particle tracking); biophysical approaches (in vitro reconstitution); biochemistry (protein expression; labelling; purification); and neuronal cell biology. There is also potential to develop super-resolution microscopy (DNA-PAINT) and CRISPR/Cas9 genome editing approaches to support the project. This research will provide fundamental insights into axonal transport, with translational outcomes for neurodegenerative diseases.
Creative individuals with an eye for detail are encouraged to apply. The successful applicant will be based in the Sheffield Institute for Translational Neuroscience, whilst working closely with both labs involved. You will be supervised by Dr Alison Twelvetrees (Dept of Neuroscience, Sheffield) and Dr Timothy Craggs (Dept of Chemistry, Sheffield). As an interdisciplinary project, applications from people from a diverse range of scientific backgrounds are welcomed e.g. cell biology, biophysics, neuroscience, biochemistry, chemistry, structural biology and biomedical sciences. Interested applicants should contact Dr Twelvetrees to discuss the project ([Email Address Removed]) with more details available on our lab website twelvetreeslab.co.uk.
Project supervisors
Dr Alison Twelvetrees; twelvetreeslab.co.uk; @dozenoaks; @TwelvetreesLab
Dr Timothy Craggs; craggs-lab.com; @Craggs_Lab
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme and how to apply can be found on our website:
http://www.dimen.org.uk/how-to-apply/application-overview
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