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The role of Myh10 (Non-Muscle Myosin IIB) in epicardial-myocardial cross talk during coronary vessel development.


Faculty of Biology, Medicine and Health

About the Project

During cardiac development the coronary vessels form from the epicardium, which is the outer epithelial cell layer of the heart. Formation of the coronary vasculature is a critical event in cardiac development, since the vasculature is required to nourish the cardiac muscle and maintain cardiac function throughout life. We have recently discovered that the gene Myh10, which encodes the protein non-muscle myosin IIB, is needed for epicardial cells to migrate onto the heart and form the coronary vessels. During this process there are signalling events between the epicardium and underlying muscle tissue of the myocardium, that direct epicardial cell migration and differentiation into vascular cell types. Signalling molecules travel through the extracellular matrix between the epicardium and myocardium, and epicardial cells migrate through the extracellular matrix to reach the heart. Interactions between the epicardium and myocardium, in the form of cross-talk, are therefore critical for the coronary vessel developmental programme.

Our characterisation of Myh10 mutants has revealed abnormalities in the production of the extracellular matrix between the epicardium and myocardium in this model. Due to the multiple functions of non-muscle myosin, it is not clear whether altered cell polarity, failed secretion, abnormal cytoskeletal structure, or abnormal composition of the extracellular matrix contributes to epicardial/myocardial signalling defects and coronary vessel failure in Myh10 mutants. In this project we seek to further understand how loss of Myh10 impacts upon the coronary vessel development process. We will evaluate signalling pathways required for coronary vessel formation and determine which are defective in Myh10 mutants. Epicardial cell polarity and secretion will be evaluated to determine if these aspects of epicardial cell function are impaired in Myh10 mutants. Overall, our studies of Myh10 mutants with abnormal coronary vasculature will determine the role of Myh10 in coronary vessel development.


Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject including developmental biology, genetics, or biomedical sciences. Candidates with experience in animal models or with an interest in cardiovascular development and disease are encouraged to apply.

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select PhD Developmental Biolody

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk



Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

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Bergeron A, Brezai A, Shukr R, Villeneuve L, Allen BG, Qureshi WMS, Hentges KE, Calderone A. Filamentous nestin and nonmuscle myosin IIB are associated with a migratory phenotype in neonatal rat cardiomyocytes. J Cell Physiol. 2020 Jul 11. doi: 10.1002/jcp.29934.

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