Diaphragmatic function in malignant hyperthermia

Project description

Malignant hyperthermia (MH) is a potentially fatal hypermetabolic reaction during general anaesthesia. Genetic predisposition to develop MH is associated with variants in genes encoding proteins involved in skeletal muscle calcium homeostasis. The gene most frequently implicated is RYR1 but variants in CACNA1S have also been described. Involvement of the diaphragm in MH has not been investigated but diaphragmatic dysfunction would be associated with reduced ventilator capacity and therefore an inability to eliminate the excessive carbon dioxide generated by the hypermetabolic response. This might contribute to resistance to therapeutic intervention and explain why fatalities still occur from MH. This project will utilise knock-in murine models of MH in which variants in either RYR1 or CACNA1S have been introduced. Studies will involve in vitro responses to MH triggering drugs, single muscle fibre studies of mitochondrial function, investigation of calcium entry mechanisms using fluorescent calcium indicators and analysis of expression levels of key gene transcripts. The effects of potential therapeutic agents will be investigated.

Entry requirements

This project is available immediately to both Home/EU rate applicants and International applicants who are able to self-fund their studies. Students must be able to provide the appropriate level of fees based on their fee status plus laboratory consumables costs per year. This is in addition to the provision of personal living expenses.

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.

Candidates whose first language is not English must provide evidence that their English language is sufficient to meet the specific demands of their study, the Faculty minimum requirements are:

• British Council IELTS - score of 6.5 overall, with no element less than 6.0
• TOEFL iBT - overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.

Applicants with sufficient funding must still undergo formal interview prior to acceptance in order to demonstrate scientific aptitude and English language capability.

How to apply

Applications can be made at any time. Potential applicants are welcome to contact Professor P M Hopkins with informal enquiries about this research project.

To formally apply for this project applicants should complete a Faculty Scholarship Application form and send this alongside a full academic CV, degree transcripts (or marks so far if still studying) and degree certificates to the Faculty Graduate School.

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly by email

If you have already applied for other scholarships using the Faculty Scholarship Application form you do not need to complete this form again. Instead, you should email fmhgrad@leeds.ac.uk to inform us you would like to be considered for this scholarship project.