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Genetic fine-mapping and functional investigation of the asthma-associated MUC5AC/MUC5B region

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  • Full or part time
    Dr K Fawcett
    Dr E Hollox
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Asthma is a common, complex disease estimated to affect over 300 million individuals worldwide. There is a need for new medicines for asthma, particularly for severe, refractory disease where current medications are not effective. In the largest genetic study of moderate-severe disease to date, we identified SNPs upstream of the MUC5AC and MUC5B genes associated with greater risk of developing severe asthma. These genes encode the two principal components of airway mucus and have altered expression and organisation in asthma patients. This studentship aims to advance these findings by; i) fine-mapping the MUC5AC/MUC5B region to identify potentially causal single nucleotide and structural variations using next-generation sequencing data from UK Biobank, ii) identifying SNP markers of structural variation and conducting a phenome-wide association study of each signal in UK Biobank to provide mechanistic insights into the association with asthma, iii) testing signals for association with clinical and immunological features of asthma using UK Biobank and specific asthma cohorts, e.g. Genetics of Asthma Severity (GASP) and iv) using in vitro models of bronchial epithelial cells collected from asthma patients and CRISPR/Cas9 genome editing to investigate the mechanisms of action of causal variants.

Entry requirements:
You must hold (or be about to obtain) a First or an Upper Second Class UK undergraduate degree or an equivalent degree from a recognised EU institution, in an area relevant to the projects you are applying for.

Qualifications (or a combination of qualifications and experience) which demonstrate equivalent ability and attainment will also be considered.

For example, a less than sufficient first degree may be enhanced to meet the requirements by the acquisition of a Distinction at Masters level or significant research experience gained from employment).

Informal enquiries:
If you have any questions or would like to find out more about IMPACT, please get in touch.
Email us at [Email Address Removed]

Eligibility:
UK/EU applicants only

To apply:
Please refer to https://more.bham.ac.uk/mrc-impact/phd-opportunities/

Funding Notes

The Studentship provides 3.5 years of Stipend at UKRI rates and Tuition fees at UK/EU rates.

References

1. Shrine N, et al. Lancet Respir Med. 2019 Jan;7(1):20-34.



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