Migraine pain: unravelling the mechanisms driving central sensitization in chronic migraine

Details

Are you passionate about advancing our understanding of migraine pain and contributing to the development of effective treatments? We invite applications for a fully-funded interdisciplinary PhD studentship at the university of Sheffield, supported by the Neuroscience Institute. Migraine is a pervasive, debilitating, multi-symptom disorder, characterised by pain and associated symptoms such as aura, nausea, vomiting, and extreme sensitivity to light, sound, movement and touching the skin. It poses a significant societal challenge due to the increasing incidence of migraine sufferers, the limited treatment options and the increasing progression to chronic migraine. This project aims to delve into the mechanisms of central sensitisation, a key player in the progression from episodic to chronic migraine. Trigeminovascular-mediated central sensitisation is implicated in severe headache, cutaneous allodynia, and resistance to certain medications. Yet, the underlying mechanisms remain elusive.

This research aims to identify subtypes of neurons affected in preclinical migraine, by investigating the mechanisms involved in the central sensitisation and the chronification of migraine, driven by the following research aims:

• Characterization of Neuronal Phenotypes: Investigate the responses of trigeminal and dorsal root ganglion neurons to acute migraine triggers using a range of methods including electrophysiology, calcium imaging, qPCR, western blot and immunocytochemistry.
• Identification of Neuronal Phenotypes for Chronification: Explore neuronal phenotypic changes associated with the chronification of migraine.
• In Vitro Migraine Modeling: Develop an in vitro model using the MED17.11 cell line to study migraine, providing an alternative to primary sensory neuron cultures.

Bringing together a dynamic interdisciplinary team with the expertise in migraine, electrophysiology, calcium imaging, cell biology, and neuroscience the findings of this project could pave the way for the development of new and effective targets for migraine treatment.

Student support and development: The PhD student will receive training in the development and usage of molecular, cellular, functional, histological, and in vivo approaches. Including cell culture, calcium imaging, molecular biology assays, immunocytochemistry, and in vivo behaviours, which will equip them with a desirable and highly competitive skillset. They will also be trained in isolation of trigeminal dorsal root ganglia. The PhD student working on this project will receive comprehensive support in their scientific training and career development, including support with conference attendance, writing and presentation skills development; the latter via weekly journal club meetings and lab meetings, at which the student will have ample opportunities to present their work in a supportive and constructively critical environment. The University, the School of Clinical Dentistry, the School of Biosciences, and the Neuroscience Institute organise many seminars and workshops that the student can benefit from and contribute to. The University also provides mentoring and career services and runs several active programmes supporting PhD students towards research independence.

Interviews are likely to be held between 4 – 15 March. Students must be able to start by October 2024.

Applications are open to students from both the UK and overseas. 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).

Please ensure you pick the Department/Division of Neuroscience when filling in your application form, regardless of where your first supervisor sits.