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Using statistical and functional analysis to investigate the contrasting disease specific roles of IL6R and the chr17q12 locus in the development of rheumatoid arthritis and asthma

Faculty of Biology, Medicine and Health

About the Project

The Arthritis Research UK and Respiratory Centres at the University of Manchester have extensive research programmes investigating the genetic components of rheumatoid arthritis (RA) and asthma. This project will initially focus on 2 associated loci; the IL6R gene and a region on chr17q12. It is already established that variants within these regions have opposing effects on the genetic susceptibility to asthma and RA. Because asthma and rheumatoid arthritis are thought to result from different immune responses this is an interesting mechanism in which to study disease causation for both diseases.

This project will uncover the causative genetic variant(s) underlying the associations in chr17q12 with asthma and RA, and explore the differing functional mechanism of the causative variant in IL6R.

The project will involve a wide range of laboratory and analytical techniques. Previously generated genotype data will be statistically analysed to determine the disease associated risk haplotype(s). This information will be used to select samples for downstream functional analysis. Novel genetic variants, including single nucleotide polymorphisms, insertions/deletions as well as transcription isoforms in the region will be catalogued using next-generation sequencing. The relationship between risk haplotype and transcription of genes in the region (eQTL) will be assessed on primary sorted cells (MACS), using techniques such as nanoString, OpenArray and RNA-seq. The mechanism by which the candidate causative genetic variant exerts its effect on the gene will be assessed using techniques such as chromosome conformation change (3C) and chromatin precipitation (ChIP). Publically available bioinformatics resources, including those generated from the encode project and 1000 genomes will be utilised throughout this project.

The project has potential for future clinical impact. Improved annotation of biological pathways important in determining disease susceptibility will lead to; sub grouping patients for better targeting treatments (stratified medicine).

The successful candidate will be trained in a wide-range of research methods such as extensive training in association analysis, next generation sequencing, bioinformatics analysis for sequence data, cell sorting and RNA analysis amongst other areas.

Applicants should hold (or expect to obtain) a minimum upper second class honours degree (or equivalent) in a relevant biological/medical science, molecular biology or related discipline. A Masters qualification in a similar area and/or previous research experience would be advantageous.

This 3-year full-time PhD is open to candidates able to provide evidence of self-arranged funding/ sponsorship and is due to commence from January 2020.

Any enquiries relating to the project and/or suitability should be directed to Dr Curtin. Applications are invited on an on-going basis but early expression of interest is encouraged.

Funding Notes

This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.

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