Unravelling the mechanisms behind inherited heart disease through time-resolved microscopy

In the heart, muscle contraction is powered by the molecular motor beta-cardiac myosin. Mutations within cardiac myosin are associated with inherited heart disease. Although we have structures of many stages of the myosin contractile cycle there is a paucity of information on how beta-cardiac myosin mutations that cause cardiac dysfunction affect myosin structure and mode of action throughout the different stages of the contractile cycle. This can be tackled by trapping the different functional states influenced by mutation by time-resolved cryo-EM

Objectives:

 (1) To express and purify a range of cardiac myosin mutants that influence activity and cause disease.

(2) To use time-resolved cryo-EM to trap different catalytic states of different mutated forms.

(3) To integrate the data to produce a detailed model of myosin force generation and mechanism of action in normal and mutated protein.

Experimental Approach: Robust protocols for protein production will be used to generate different mutants. These will be studied by both conventional cryo-EM and new time-resolved methodologies to trap non-equilibrium states. Full training in all aspects is available and you will be part of a large, dynamic and supportive environment with a focus on protein structure/function studies.

Eligibility: 

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

Applicants 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 of Biological Sciences minimum requirements in IELTS and TOEFL tests are:

• British Council IELTS - score of 6.0 overall, with no element less than 5.5
• TOEFL iBT - overall score of 87 with the listening and reading element no less than 20, writing element no less than 21 and the speaking element no less than 22.

How to apply:

To apply for this project applicants should complete an online application form and attach the following documentation to support their application. 

• a full academic CV
• degree certificate and transcripts of marks
• Evidence that you meet the University's minimum English language requirements (if applicable).

To help us identify that you are applying for this studentship please ensure you provide the following information on your application form;

• Select PhD in Biological Sciences as your programme of study
• When asked for source of funding please make it clear that you are applying for a "White Rose BBSRC DTP Studentship"
• Give the full project title and name the supervisors listed in this advert. You can be considered for up to 3 projects in total.

If you have any further queries regarding this opportunity, please contact [Email Address Removed]