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Identification of blood biomarkers for antenatal diagnosis of a common congenital heart defect, Tetralogy of Fallot.

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  • Full or part time
    Dr I Dykes
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Almost 1 in every 100 babies born in the UK has a congenital heart defect (CHD). CHD is the leading cause of infant mortality and affected children often require surgery at birth. Early antenatal detection provides the opportunity for parents to make informed decisions and can result in better clinical outcomes. Diagnosis is normally based on a cardiac ultrasound scan, which is offered universally in the UK at ~20 weeks. Invasive screening, such as chorionic villus sampling, carries a risk of miscarriage and thus is not routinely offered. Despite improvements in rates of antenatal detection, 50% of CHDs are currently undiagnosed until birth. There is a clinical need for an accurate non-invasive maternal blood test.

The aim of this project will be to identify biomarkers of CHD present in the blood of pregnant women which will allow development of a non-invasive blood-based antenatal CHD diagnostic test that will enable early diagnosis without endangering the unborn child. Pregnant women carrying babies with the congenital condition Tetralogy of Fallot (commonly known as a hole in the heart) will be recruited at the antenatal clinic at Alder Hey Children’s Hospital. Maternal blood samples will be collected, together with matched patient heart tissue discarded during corrective surgery at Alder Hey, and compared to blood from women carrying healthy pregnancies.

Exosomes have proven potential as disease biomarkers in cancer and cardiovascular medicine. Exosomes are small membrane-bound extracellular vesicles present in blood and other body fluids which function in endocrine signalling during both health and disease. Increased exosome levels are associated with pregnancy. Exosomes carry a cargo of micro RNA (small RNA molecules which regulate gene expression), and express glycoprotein epitopes on their surface. Both of these may be exploited as biomarkers. We will extract exosomes from plasma before analysing micro RNA (e.g. qRT-PCR, Nanostring profiling) and glycoprotein epitope expression (e.g. immuno flow cytometry).

The successful applicant will benefit from a multidisciplinary supervisory team including both basic scientists and clinicians. The director of studies, Dr. Iain Dykes, is an expert in the molecular biology and genetics of embryonic heart development. The team also includes Dr. Andrew Powell, a biochemist with expertise in immunoassays and bioanalytical methods, Dr. Robyn Lotto an expert in clinical practise with extensive experience in NHS patient recruitment, and Mr. Attilio Lotto, a congenital heart surgeon based at Alder Hey Children’s hospital. All are members of the recently created Liverpool Centre for Cardiovascular Science, a collaboration between Liverpool John Moores University, Liverpool University and several local hospitals.


Eligibility requirements

Applicants are invited who possess a B.Sc. (minimum 2:i) or M.Sc. in a relevant subject area. We are seeking a highly motivated candidate who is committed to pursuing a career in academic research. Due to funding restrictions, only UK & EU citizens are eligible to apply for this studentship.

How to Apply

For an informal discussion about this position please contact Dr. Iain Dykes ([Email Address Removed]).

Applications should include a CV, a covering letter detailing your motivation in applying for the project, and the contact details of two referees. Applications should be sent directly to Dr. Iain Dykes ([Email Address Removed]) by 1st December 2019.

We expect to conduct interviews early in December, and the successful applicant will start on 7th February 2020.

Funding Notes

This studentship is funded by the Faculty of Science, Liverpool John Moores University and was created to celebrate the opening of the Liverpool Centre for Cardiovascular Science. The studentship covers full tuition fees for the three year duration of the award, together with of a stipend paid at UK Research Council rates (currently £15,009 p.a., tax free).

References

Dykes, I. M. (2017). Exosomes in Cardiovascular Medicine.
Cardiology & Therapy 6, 225-237. doi:10.1007/s40119-017-0091-9

Lotto, R. R., Jones, I. D., Guerrero, R., Dhannapuneni, R. & Lotto, A. A. (2019)
Congenital cardiac surgery and parental perception of risk: a qualitative study.
Cardiology in the Young, 1-7. doi:10.1017/S1047951119002087.

Powell, A. K., Ahmed, Y. A., Yates, E. A. & Turnbull, J. E. (2010)
Generating heparan sulfate saccharide libraries for glycomics applications.
Nature Protocols 5, 821-833, doi:10.1038/nprot.2010.17



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