PhD Studentship in Epigenetics - Using chromatin interaction analysis and CRISPR-Cas9 mediated genomic editing to identify the target genes of osteoarthritis-associated transcriptional regulatory elements

Number of awards:

1

Start date and duration:

September 2018 for 3 years.

Overview:

Osteoarthritis (OA) is a chronic musculoskeletal disease that affects the synovial joints, including hips and knee. OA is the leading cause of chronic disability in the UK, affecting 8.5 million people. There are currently no disease modifying drugs available, and in order to aid diagnosis and identify new therapeutic targets, increased understanding of the molecular mechanisms underlying the disease process is required.

Changes in epigenetic mechanisms of regulating gene expression, including altered DNA methylation, have been identified as a significant contributing factor to the pathogenesis of OA. DNA methylation levels in enhancer regulatory elements are known to reflect their activity. Previous genome-wide analysis comparing healthy and OA tissue has identified that the majority of OA-associated DNA methylation changes map to non-coding intronic or intergenic regions of the genome with enhancer features. However, the target genes of these putative enhancers are largely unknown as regulatory regions often do not regulate the nearest gene.

This project will use a range of molecular biology techniques and bioinformatics analysis to identify the target genes of these enhancers and what affect the OA- associated DNA methylation changes have on gene expression. The student will perform chromatin interaction analysis using Capture-C, a technique used to identify DNA loci that physically interact, to identify the promoters that interact with the OA-associated enhancers. To validate the function if the enhancers, cutting edge CRISPR/Cas9 nuclease genome editing technology will be employed to genetically ablate and epigenetically modify the regulatory element and evaluate if these perturbations affect the expression levels of the target genes.

This exciting studentship will derive valuable new molecular insights into OA pathogenesis by identifying genes subject to OA-associated epigenetic changes, some of which may be novel diagnostic and therapeutic targets.

Sponsor:

Newcastle University, Faculty of Medical Sciences

Name of supervisor(s):

Dr Louise Reynard (https://bitly.im/ApZpW), Institute of Genetic Medicine (https://bitly.im/PY3Rc)

Dr Daniel Rico, Institute of Cellular Medicine (http://www.ncl.ac.uk/icm/people/profile/danielrico.html#background)

Professor David Young, Institute of Genetic Medicine (http://www.ncl.ac.uk/igm/staff/profile/davidyoung.html#background)

Eligibility Criteria:

You must have, or be expected to have a First class BSc (Hons) or a Masters degree in biomedicine, biological sciences, or a related area.

This award is available to UK/EU applicants. To study this course you need to meet the following English Language requirements: IELTS 6.5 overall (with a minimum of 5.5 in all other sub-skills).

How to apply:

You must apply through the University’s online postgraduate application system (https://bitly.im/Bfkt2). To do this please ‘Create a new account’.

Only mandatory fields need to be completed. However, you will need to include the following information:
•insert the programme code 8300F in the programme of study section
•select ‘PhD in the Faculty of Medical Sciences – Medicine Genetics as the programme of study
•insert the studentship code GM002 in the studentship/partnership reference field
• attach a covering letter and CV. The covering letter must state the title of the studentship, quote the studentship reference code GM002 and state how your interests and experience relate to the project
•attach degree transcripts and certificates and, if English is not your first language, a copy of your English language qualifications.