Epilepsy can affect all ages, but it is more prevalent in the elderly and often induced by traumatic brain injury (TBI) and neurodegenerative disease. What makes the ageing and TBI brain more vulnerable to seizures and epilepsy is unknown.
Various subcellular changes have been described for neurons in the ageing brain, amongst them the deterioration of the microtubule cytoskeleton. Microtubules are key mediators of neural communication, essential for synaptic organisation and function. Microtubule alterations are also observed in brain trauma and neurodegeneration including Alzheimer’s and Parkinson’s. Even though microtubule decay occurs in several conditions known to increase risk of epilepsy, microtubule decay has not been properly explored as a common cause in adult epilepsy.
The aim of this studentship is to investigate a novel pathological path of adult-onset epilepsy, through the study of microtubule decay as a key mechanism that increases the risk to develop epilepsy during ageing, TBI and neurodegenerative conditions. You will be part of a multidisciplinary collaboration between 3 experienced groups at the Institute of Systems, Molecular & Integrative Biology (ISMIB, University of Liverpool), the York Biomedical Research Institute (University of York) and the Division of Neuroscience at the School of Biological Sciences (University of Manchester).
You will use Drosophila, a highly efficient and well-established model for ageing and epilepsy research. Drosophila neurons show characteristic ‘human-like’ ageing pathologies in few weeks, have highly conserved microtubule regulators, and their epilepsy-related synaptic proteins are conserved to a degree that human anti-epileptic drugs can effectively suppress seizures. The project will be broken down into four objectives: a) To validate our preliminary results that ageing and neurodegenerative conditions increase the incidence of epilepsy; b) to prove that microtubule deterioration is a potential causative factor for epilepsy; c) to establish whether aberrant axonal transport and localisation of synaptic proteins are key epilepsy-inducing factors, downstream of microtubule decay; d) to explore the use of microtubule-stabilising interventions as potential antiepileptics. Investigating this novel trio of ageing, epilepsy and the microtubule cytoskeleton will advance our understanding of adult-onset epilepsy.
This studentship represents a unique opportunity to receive training in timely techniques. With its multidisciplinary approach, the student will be trained on behavioural tests consisting of seizure-induction assays as well as motility assays and whole-organism electrophysiology.
We will use advanced live imaging techniques combined with cellular biology. The student will also be trained in genetic and/or pharmacological manipulation and anatomical studies of the brain in vivo.
Creative individuals with an eye for detail are encouraged to apply. The successful applicant will be based in Liverpool, at the Institute of Systems, Molecular & Integrative Biology supervised by Dr. Sanchez-Soriano, whilst working closely with Dr Ines Hahn at the Department of Biology in York, and Prof. Richard Baines at the University of Manchester. Applications from candidates, ideally with some background in cell biology or genetics and neuroscience are welcome. Interested applicants should contact Dr Sanchez-Soriano to discuss the project: firstname.lastname@example.org.
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: https://www.dimen.org.uk/blog
Further information on the programme and how to apply can be found on our website: https://www.dimen.org.uk/how-to-apply
Open to students worldwide
Studentships are fully funded by the Medical Research Council (MRC) for 4yrs. Funding will cover tuition fees, stipend (£18,622 p.a. for 2023/24) and project costs. We also aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of full studentships to international applicants. Please read additional guidance here: View Website
Studentships commence: 1st October 2024
- Voelzmann, A., et al. (2016). "Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking." eLife 5.
- Mattison, K. A., et al. (2023). "ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy." Brain 146(4): 1357-1372.
- Dyson, A., et al. (2022). "Loss of NF1 in Drosophila Larvae Causes Tactile Hypersensitivity and Impaired Synaptic Transmission at the Neuromuscular Junction." The Journal of neuroscience : the official journal of the Society for Neuroscience 42(50): 9450-9472.
- Mulroe, F., et al. (2022). "Targeting firing rate neuronal homeostasis can prevent seizures." Dis Model Mech 15(10).
- Hahn, I., et al. (2021). "Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons." PLoS Genet 17(7): e1009647. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009647