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Genetic and immunological basis of rare primary immunodeficiency diseases

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  • Full or part time
    Dr P Arkwright
    Dr T Briggs
    Prof T Hussell
  • Application Deadline
    Applications accepted all year round

Project Description

Objective: To understand the genetic and explore the functional immune basis of rare primary immunodeficiency diseases

Background: Royal Manchester Children’s Hospital is the main referral centre for children with confirmed or suspected immunodeficiency disorders. Over the last ten years, we have been part of the team which has used new generation sequencing to identify novel immunogenetic disorders in over fifty children. Our database still contains a group of a further fifty children where the diagnosis remains elusive. We have DNA stored on all these patients and cells lines for further functional work on many. The aim of this PhD project is the revisit the genetic and biological basis of these patients’ diseases using the latest genomic, bioinformatic and functional assays available in our recently formed Immunology Institute.

Methods: Whole exome and genome sequencing will be undertaken, or available data reviewed, in clinically affected individuals. Using an established bioinformatic pipeline, analysis will be undertaken to identify candidate variants in novel disease-causing genes. Sanger sequencing to allow variant confirmation and segregation analysis will then be performed. Relevant transcriptomic and proteomic studies will be undertaken to assess the consequence of the identified candidate genetic variant on RNA and protein expression. Depending on the genes affected we will interrogate the functional consequences on relevant immune cells. For example, previously we have identified defects in a gene that has predominant activity in neutrophils. The ability of neutrophils with the gene modification were examined for their ability to recognise and engulf bacteria. We also determined any influences on inflammatory mediator production.

Potential outcomes: The expected outcome is the identification of the genetic and biological basis of new immune disorders causing serious infections or inflammatory responses. It is expected that these findings will be presented at relevant national and international meetings and published in high impact journals.

Entry Requirements: Candidates are expected to hold (or be about to obtain) a minimum upper second-class honours degree (or equivalent) in the general area of genetics, bioinformatics or immunology and preferable have completed an MSc in one of these areas. Candidates with experience or an interest in molecular biology and immunology are encouraged to apply. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website ( Informal enquiries may be made directly to the primary supervisor.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit

Funding Notes

Applications are invited from self-funded students. For UK/EU tuition fees are £20,000 and International are £34,500 for 2018/19 academic year.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.


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2. Cuchet-Lourenco D et al. Biallelic RIPK1 mutations in human cause severe immunodeficiency, arthritis, and intestinal inflammation. Science 2018, Aug 24.
3. van De Geer A et al. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest 2018;128:3957-3975.
4. Israel L et al. Human adaptive immunity rescues an inborn error of innate immunity. Cell 2017168;789-800.
5. Martin E et al. CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature 2014;510:288-92.

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