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Using multi-omics data to understand the links between DNA and disease

  • Full or part time

    Prof E Pearson
  • Application Deadline
    Friday, April 26, 2019
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Genome-wide association studies have produced thousands of associations between DNA loci and risk of disease, but in most cases the immediate processes are unclear. To address this problem, a number of consortia have collected multiple omics phenotypes, to understand how genetic variation affects cellular processes and the downstream consequences for disease. The aim of this project will be to develop methods to combine genetic data, high dimensional omics data and information on disease status to elucidate the causal pathways. This will be done using publicly available data and as part of consortia that we are involved in. Initially there will be a focus on the genetics of Type II diabetes, due to the experience within the department in this disease and the role we play in the DIRECT consortium, which has gene expression and proteomics data from a diabetes case control study.

Future lines of inquiry include:
Co-localisation analysis of omics and disease associations.
Methods for mapping causal variants using high dimensional data.
Developing transcriptome wide association methods in case control cohorts.
Context dependent genetic effects.
Heritability and genetic correlations between omic phenotypes.

Requirements

The candidate should have:
A strong desire to work on disease related questions using high dimensional data and computational methods.
A willingness to interact with people from many specialities, including biologists, clinicians, computer scientists and statisticians.
Keeness to present their research findings within consortia and at international meetings.

Some background in the following areas would be an advantage, but are not necessary, as attaining a level of fluency in these areas is expected over the course of the PhD:

Genetic regulation of gene expression or protein levels.
Genetic studies into disease.
Type II diabetes.
Computer programming with either high or low level languages.
Statistics and knowledge of a statistical programming language.

Benefits of pursuing a PhD in the University of Dundee
The University of Dundee aims to become Scotland’s leading University in all it chooses to do and be recognised internationally for the quality of our graduates and the impact of our research. These research and teaching strengths have led to the University being named as Scottish University of the Year in both 2016 and 2017 in The Times & Sunday Times Good University Guide, and named the 16th best university in the world under 50 years old (Times Higher Education World University Rankings 150 under 50 2016).

Dundee, the City of Discovery, is a modern and vibrant city set in a stunning location at the mouth of the River Tay on the east coast of Scotland with a population of approx. 148,000. The city benefits from a central geographic location, with 90% of Scotland within 90 minutes’ drive. The “thriving, creative” city of Dundee was rated one of the best places in Europe to visit by Lonely Planet (2018). Dundee, the Lonely Planet said, deserves its place in the top ten because of its head-turning transformation and “nationally important museums and attractions”.

Future prospects
Data science is an area into which both the public and private sectors are putting a great deal of resources, and the ability to discover patterns in high dimensional data is a highly employable skill. The University of Dundee is one hub of the network of Health Data Research-UK sites that the government has set up to facilitate the sharing of data for clinical research. Pharmaceutical companies are also exploring how sequencing data can be integrated into their drug pipelines: GlaxoSmithKline has entered into a partnership with 23andMe for just this purpose, using many of the methods that will be explored in this project. As such, we would expect by the end of the research programme that the individual selected would be well placed to pursue a career either in academia or in the private sector.

Apply
Applicants wishing to apply should submit a one-page covering letter which describes your background, your reasons for applying, and your future career aspirations and also a full CV and contact details for two referees to Dr. Andrew Brown,

Funding Notes

This is a 3 year fully-funded PhD studentship which covers fees, a stipend and a budget for consumables and travel.

References

Brown et al. Predicting causal variants affecting expression using whole genome sequence and RNA-seq from multiple human tissues. Nature genetics, 2017.
The GTEx Consortium. Genetic effects on gene expression across 44 human tissues. Nature, 2017.
Ongen et al. Estimating the causal tissues for complex traits and diseases. Nature genetics, 2017.
Brown et al. Genetic interactions affecting human gene expression identified by variance association mapping. eLife, 2014.

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