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MRC DTP 4 Year PhD Programme: Mendelian Randomisation Approaches to defining the Underlying risk factors for the Dementias.

  • Full or part time
    Dr A Doney
  • Application Deadline
    Saturday, January 11, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

This project is offered as part of the University of Dundee 4-year MRC DTP Programme “Quantitative and Interdisciplinary approaches to biomedical science”. This PhD programme brings together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its very high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK. A wide range of projects are available within this programme crossing exceptional strengths in four key areas: Infection and Disease; Responses to Cellular Stresses; Development, Stem Cells and Neurobiology; and Big Data and Translation. All students on this programme will receive training in computational biology, mathematical biology and statistics to equip with the quantitative skills in tackling complex biological questions. In the 1st year, students will carry out 3 rotation projects prior to selection of the final PhD project.

Our brain defines who we are and keeping the brain healthy as we get older is one of the most urgent of all social and medical challenges. Alzheimer’s disease together with other dementias are by far the most common causes of reduced brain health and have become the leading cause of long-term disability and death in the UK. Unfortunately, attempts to find treatments to cure dementia once it has started have not been successful. The focus of research is shifting towards identifying major long-term health conditions such as high blood pressure or being over-weight that drive the risk for developing dementiain the future. This may allow established medicines used to manage these conditionstobe repurposed to slow down or prevent dementia from developing. Many thousands of people in Scotland over many years have contributed to bioresources where their genetic information is linked to their health care records. Many of these people have aged and have now developed dementia. We have been using these resources to investigate the risk factors for the development of dementia making use not only of clinical information in the medical records but also information contained in the human genome. Genetic information is being increasingly used to undertake “Mendelian Randomisation” studies. This powerful approach relies on the random process by which we inherit the genetic variants we carry through life. This makes it is possible to conduct the equivalent of randomised controlled trials to investigatethe clinical effect of a medicine ona clinical conditions or outcomesby exploitingthe specific phenotypic effects of inherited genetic variants.

In this PhD the candidate will work within an experienced team with access to a large and internationally renowned bioresource. Extensive genomic data will be linked to high density long term biomedical data anda series of powered Mendelian randomisation studieswill be undertaken,making use of polygenic risk scores,to explore the clinical and molecular determinants of future brain health. This will inform on futureopportunities for doctors to manage dementia risk pharmacologicallyand through lifestyle to maximise and preserve brain health in the long term.

References

Recent work from the lab can be found in the following references:

Doney, A. S. F. et al.Investigating the Relationship Between Type 2 Diabetes and Dementia Using Electronic Medical Records in the GoDARTS Bioresource. Diabetes Care42, 1973–1980 (2019).

Tornio, A. et al.Investigating Real-World Clopidogrel Pharmacogenetics in Stroke Using a Bioresource Linked to Electronic Medical Records. Clin. Pharmacol. Ther.103, 281–286 (2018).

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