Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The Z-disk is not only a crucial structural part of the sarcomere, but also thought to be a signalling hub for sensing and responding to biomechanical stress. This is highlighted by the fact that mutations in Z-disk proteins can cause inherited heart or skeletal muscle disease, however the underlying signalling pathways are poorly understood.

We have identified missense mutations in Z-disk proteins causing cardiomyopathies. In vivo animal models carrying these mutations will be generated and cardiac phenotyping be performed. Additionally the models will be challenged by e.g. chronic stimulation of adrenergic pathways or through aortic constriction. Ex vivo studies on the hearts from these models will be used to gain insight into disturbance of Z-disk structure and signalling functions. In addition to hypothesis-driven experiments, RNAseq and mass spectrometry approaches will generate novel hypotheses how disturbed Z-disk signalling results in cardiac disease. Newly identified pathways will also be explored in skeletal muscle should the animals display a skeletal muscle phenotype.

Training Opportunities

Work with in vivo models (mouse) of human disease: Assessment of cardiac function in vivo by echocardiography and invasive haemodynamic measurements; chronic administration of drug. Ex vivo characterisation of a molecular phenotype: qPCR, Western blotting, immunofluorescence, histology, electron microscopy Hypothesis-generating approaches: RNAseq and mass spectrometry Data generation, analysis, interpretation and presentation

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford. Students are also able to attend the Methods and Techniques course run by the MRC Weatherall Institute of Molecular Medicine. This course runs through the year, ensuring that students have the opportunity to build a broad-based understanding of differing research techniques.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to support the careers of female students and staff.

Publications

1 Ribeiro Ede A, Pinotsis N, Ghisleni A, Salmazo A, Konarev PV, Kostan J, Sjöblom B, Schreiner C, Polyansky AA, Gkougkoulia EA, Holt MR, Aachmann FL, Zagrović B, Bordignon E, Pirker KF, Svergun DI, Gautel M, Djinović-Carugo K. 2014. The structure and regulation of human muscle α-actinin.Cell,  159 (6), pp. 1447-60. - http://www.ncbi.nlm.nih.gov/pubmed/25433700
2 Hastings R, de Villiers CP, Hooper C, Ormondroyd L, Pagnamenta A, Lise S, Salatino S, Knight SJ, Taylor JC, Thomson KL, Arnold L, Chatziefthimiou SD, Konarev PV, Wilmanns M, Ehler E, Ghisleni A, Gautel M, Blair E, Watkins H, Gehmlich K. 2016. Combination of Whole Genome Sequencing, Linkage, and Functional Studies Implicates a Missense Mutation in Titin as a Cause of Autosomal Dominant Cardiomyopathy With Features of Left Ventricular Noncompaction.Circ Cardiovasc Genet,  9 (5), pp. 426-435. - http://www.ncbi.nlm.nih.gov/pubmed/27625337

Research Themes, Tools and Technologies

Supervisors

Key Dates for October 2018 Entry

Application deadline:  12 noon GMT on Monday 8 January 2018

Interviews for shortlisted candidates: Week commencing Monday 22 January 

Find out more

How to apply

To apply for a place on the DPhil in Medical Sciences you will need to submit an application using the online application form.

Find out more