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Epigenetic mechanisms in atrial fibrillation – the role of developmental regulators and chronic stress

Blizard Institute

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Dr D Villar Lozano , Prof A Tinker No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

This is an exciting opportunity for a PhD studentship within the supportive learning environment of the Blizard Institute and the wider Barts and The London School of Medicine and Dentistry (SMD) at QMUL. Applications are invited for a four-year PhD studentship to support an ambitious student with a strong background in molecular biology and genetics. Applicants should have a good Honours degree in Biochemistry, Molecular Biology or related disciplines (minimum 2(i) or equivalent), experience of conducting research (either experimental or computational) and a strong interest in molecular genetics and genomics. Previous experience with genomic technologies, bioinformatics or animal disease models would be advantageous.

Project background:

The development of cardiac arrhythmias is associated with an increased susceptibility to heart diseases with a high societal burden, such as heart failure and sudden cardiac death. Atrial fibrillation is the most common form of arrhythmia (affecting around 2% of the general population), and recent population-wide research indicates it has a high genetic heritability. New knowledge of the regions in our DNA associated to susceptibility of this disease point to an important role of gene regulatory processes, yet the molecular mechanisms leading to atrial fibrillation are poorly understood. Moreover, the disease often occurs in patients presenting with cardiac and respiratory stress, such as sleep apnea and chronic obstructive pulmonary disease. However, it is unclear how these pre-existing conditions may affect arrhythmia susceptibility.

The project aims to improve the mechanistic understanding of atrial fibrillation. To achieve this, it will focus on addressing the contributions of gene regulatory processes to disease development and progression. Specifically, the student will conduct and integrate genomic experiments across patient samples (from our NIHR BRC) and several models of atrial heart muscle function, with the following objectives:

(i) to measure epigenetic changes in atrial fibrillation patients, associate them with gene expression changes, and computationally identify candidate disease-associated regions.

(ii) to interrogate the role of transcription factors genetically linked to the disease in humans, by exploiting an in vitro differentiation model of atrial development and CRISPR/Cas9 epigenetic editing.

(iii) to assess the interaction between atrial fibrillation and chronic hypoxia, combining in vitro and in vivo models.

These studies will be conducted in a multi-disciplinary and collaborative learning environment across the QMUL SMD, which includes an excellent training and support network within the Blizard Institute. Over the course of the studentship there will be ample opportunities for interaction with epigenetics experts (QMUL Epigenetics Hub), cardiovascular geneticists (co-supervisor Prof. Andrew Tinker) and clinical specialists (Prof. García Rio).

Interviews are planned for March 2020.

Funding Notes

The studentship is fully funded for 4 years by the Barts Charity and will commence on or around Spring 2020 (start date will be discussed with individual applicants). Funding includes university fees, £7,000 annual consumables and a minimum tax-free stipend of £24,000 per annum.
This studentship is open to UK and European Economic Area citizens.
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