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Exploring the structural basis of inherited heart disease with cryo-electron microscopy, mass spectrometry and modelling

Faculty of Biological Sciences

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Dr C A Scarff , Dr SA Harris , Dr J.R. Ault No more applications being accepted Funded PhD Project (UK Students Only)

About the Project

Hypertrophic cardiomyopathy is an inherited heart disease affecting more than 1 in 500 people and is the most common cause of heart failure in the young. The link between inherited mutation and disease outcome is poorly understood so we can only treat the symptoms and not the cause. Most mutations resulting in disease are found in key structural proteins of the heart muscle, such as myosin and myosin-binding protein c, but the interactions and organisation of these proteins is not completely understood at the molecular level. Increasing this understanding could lead to new therapeutic avenues for inherited heart disease.

This project will investigate the interactions of muscle thick filament proteins and test how small molecules and mutations influence these interactions. The project will use a combination of molecular and structural biology, and biophysical methods, to fulfil these aims. These will include molecular cloning, protein expression and purification, electron microscopy, hydrogen-deuterium exchange mass spectrometry, computational modelling, and in silico-based drug design. Through this combination of structural biology and biophysical techniques, we can significantly improve our understanding of interactions within the muscle thick filament in health and disease. This work has the potential to lead to new therapeutic avenues for inherited heart disease. The candidate will benefit from working in a vibrant community of students and postdocs within structural and molecular biology, cardiovascular science, and biophysics.

Funding Notes

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”. This is a fully funded studentship, providing UK/EU fees plus stipend for 3.5 years

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