Join a team of experts to investigate the molecular mechanisms that underlie neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis. This project focuses on two common molecular mechanisms that underlie neuronal dysfunction and degeneration in each disease; axonal transport dysfunction and DNA damage repair. We are seeking a creative individual with an eye for detail to explore the potential of newly discovered functions of the NuMA protein.
Ageing-related neurodegenerative diseases lead to a decline in cognitive and motor function and death. Each disease is characterised by loss of specific subsets of neurons, and symptoms unique to each disease are used for diagnosis. Despite these differences, common molecular mechanisms underlie neuronal dysfunction and degeneration in each disease. Two molecular mechanisms with key pathogenic roles in neurodegeneration, axonal transport (Twelvetrees) and DNA damage repair (El-Khamisy), are the focus of the supervisory team. Axonal transport supports the continuous supply of critical cellular machinery synthesised in the cell body, and is powered by motor proteins walking along microtubule filaments. Disruptions to axonal transport machinery are extensively linked to neurodegenerative disease, and axonal transport declines with age. DNA damage can occur due to oxidative stress, exposure to toxic chemicals, and normal cellular processes, leading to alterations in gene expression that contribute to neurodegeneration. Genetic mutations that affect the DNA damage response, including genes involved in DNA repair, increase the risk of developing neurodegenerative diseases.
This project will focus on the protein NuMA. NuMA was originally identified as a critical component of the mitotic spindle. In recent work by the team of Prof El-Khamisy, it was discovered that NuMA is essential for repairing the damage to DNA caused by oxidative stress. NuMA has also recently been linked to microtubule organisation in the axon. These discoveries highlight a new possibility, that NuMA could be key to both axon maintenance and the DNA damage response in ageing neurons.
As a PhD student on this project, you will gain training in quantitative and computational skills, applied to analysing real-time imaging and single-molecule data. In parallel you will also receive training in advanced tissue culture techniques and cellular and molecular neurobiology. You will be part of a new, multidisciplinary collaboration between the Twelvetrees lab (twelvetreeslab.co.uk) at the Sheffield Institute for Translational Neuroscience (SITraN) and the El-Khamisy lab (elkhamisylab.com) in the School of Biosciences at the University of Sheffield.
This interdisciplinary project welcomes applicants from a diverse range of scientific backgrounds, including but not limited to cell biology, biophysics, neuroscience, biochemistry, chemistry, and biomedical sciences. Join us in discovering new possibilities for therapeutic intervention and promoting healthy neuronal ageing. Interested applicants should contact Dr Twelvetrees to discuss the project ([Email Address Removed]).
Further background information can be found on our lab websites:
twelvetreeslab.co.uk
elkhamisylab.com
----------------------------------------------
Please see this link for information on how to apply: https://www.sheffield.ac.uk/postgraduate/phd/apply. Please include the name of your proposed first supervisor and the title of the PhD project within your application.
Interviews will likely be held in April. Students must be able to start by October 2023.
Applications are open to students from both the UK and overseas, though we note that due to funding constraints the availability of positions for students with overseas fee status will be more limited. We anticipate competition for these studentships to be very intense. We would expect applicants to have an excellent undergraduate degree in a relevant discipline. We would also expect applicants to have completed or be undertaking a relevant master’s degree to a similar very high standard (or have equivalent research experience).
Continue with Facebook
