Qualification: PhD

Department: Cardiovascular Sciences

Application deadline: 4 July 2021

Start date: September 2021

Overview

Supervisors:

Project description:

Bicuspid aortic valve (BAV), which affects 1% of the general population, is the most common congenital valvular heart disorder. In affected individuals, the aortic valve (the structure that allows blood to flow from the left ventricle to the aorta) consists of two rather than three leaflets. Despite usually having a benign presentation, BAV is associated with serious cardiovascular complications later in life including aortic valve stenosis, aneurysm of the thoracic aorta and infective endocarditis. More than 50% of patients with BAV need an open-heart surgery during their lifetime.

BAV clusters within families following an autosomal dominant pattern of inheritance and causative mutations in several genes including NOTCH1, TGFBR2, GATA5 and SMAD6 have been identified, however, mutations in these genes only explain a small proportion of BAV cases. In addition, up to 85% of all BAV patients are sporadic i.e. do not have any affected relatives. The reason for this phenomenon has not been elucidated but incomplete penetrance of genetic variants and variable clinical presentation of the disease have been hypothesized.

We have recruited a large cohort of patients with BAV as part of the University of Leicester NIHR Bicuspid aoRtic vAlVe gEnetic research (BRAVE) study. The BRAVE cohort comprises more than 700 patients with sporadic BAV disease and over 20 extended pedigrees with multiple affected members. In this PhD the student will utilise this resource to identify new genes causing BAV via analysis of new sequencing data, perform functional validation and characterisation analyses of novel BAV genes and screen patients with sporadic disease to gain a better understanding of penetrance of BAV causal mutations.

References:

1. Siu SC, Silversides CK. Bicuspid aortic valve disease. J Am Coll Cardiol. 2010.55, 2789-800.
2. Cripe, L., Andelfinger, G., Martin, L. J.. lkt  e. Bicuspid aortic valve is heritable. J. Am. Coll. Cardiol. 2004,44,138–143.
3. Debiec R, Sall H, Samani NJ, Bolger A.  Genetic Insights Into Bicuspid Aortic Valve Disease. Cardiol Rev. 2017.25:158-164.
4. Debiec R, Hamby SE, Jones PD et al. Novel loss of function mutation in NOTCH1 in a family with bicuspid aortic valve, ventricular septal defect, thoracic aortic aneurysm, and aortic valve stenosis. Mol Genet Genomic Med.2020;8:e1437.

 

 

 

 

Funding

Funding

This 3-year The Thomas Herbert Wathes Centenary Scholarship provides;

  • UK/EU tuition fee waiver
  • Annual stipend at UKRI rates (£15,609 for 2021/22)

*Please note that this project is competition funded.

Entry requirements

Entry requirements

Applicants are required to hold/or expect to obtain a UK Bachelor Degree 2:1 or better (or overseas equivalent) in a biological sciences subject.

The University of Leicester English language requirements apply where applicable.

 

Informal enquiries

Informal enquiries

Project enquiries:

Application enquiries:

How to apply

How to apply

To submit your application, please use the 'Apply' button below and select September 2021 from the dropdown menu.

With your application, please include:

  • CV
  • Personal statement explaining your interest in the project, your experience and why we should consider you
  • Degree Certificates and Transcripts of study already completed and if possible transcript to date of study currently being undertaken
  • Evidence of English language proficiency if applicable
  • In the reference section please enter the contact details of your two academic referees in the boxes provided or upload letters of reference if already available.
  • In the funding section please specify that you wish to be considered for The Thomas Herbert Wathes Centenary Scholarship
  • In the proposal section please provide the name of the project supervisors and the project title (a research proposal is not required)

*If you wish to be considered for more than one Thomas Herbert Wathes Centenary Scholarship project, please include all of the relevant project and supervisory details within one application.

Eligibility

Eligibility

UK/EU applicants only