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Using structural biology to develop drugs and improve genetic testing for polycystic kidney disease


   Faculty of Biological Sciences

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  Dr J.J.B. Cockburn, Prof Colin Johnson  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

Are you looking for a PhD in structural and computational biology applied to drug development for human diseases?

This PhD project will investigate the molecular causes of autosomal recessive polycystic kidney disease (ARPKD), a rare inherited disorder that causes severe defects in kidney development. Around one third of live ARPKD births die within 4 weeks, but those surviving beyond this display a varied clinical course typically ending in kidney failure by the age of 20. This provides a treatment window that could allow medicines to improve the lives and outlook of such “survivors”. However, there are no licenced treatments for ARPKD.

ARPKD is caused by mutations in a gene called PKHD1 that encodes fibrocystin, a very large membrane protein found in cilia. Survivors harbour PKHD1 mutations that alter the sequence of fibrocystin, but the effect on the structure and function of the protein are unknown. In addition to known pathogenic mutations, there are over 700 PKHD1 mutations with unknown effects. This limits the effectiveness of genetic testing in families with a history of the disease, thus reducing the clinical utility of genetic counselling, carrier screening, prenatal testing and prognostic testing.

In this project you will investigate the structure of fibrocystin using X-ray crystallography and computational modelling and identify which mutations alter its structure and thus potentially cause disease. Furthermore, you will use X-ray crystallography, NMR and computational methods to identify small molecules that correct defects in protein structure caused by the most commonly occurring disease-causing mutation. These molecules will serve as start points to develop drugs to treat ARKPD survivors.

This Kidney Research UK-funded project will thus provide a solid training in structural and computational biology, drug development and inherited disorders, and will significantly impact the community by aiding therapeutic drug development and facilitating improvements to genetic counselling.

Eligibility

Applicants should have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. A Masters degree is desirable but not essential.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.

How to apply

To apply for this scholarship opportunity applicants should complete an online application form and attach the following documentation to support their application. 

  • a full academic CV
  • degree certificate and transcripts of marks
  • Evidence that you meet the University's minimum English language requirements (if applicable)
  • If you are an International applicant please provide evidence of additional funding to covet the deficit in academic fees

To help us identify that you are applying for this scholarship project please ensure you provide the following information on your application form;

  • Select PhD in Biological Sciences as your programme of study
  • Give the full project title and name the supervisors listed in this advert
  • For source of funding please state you are applying for a Kidney Research UK Scholarship

As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Within the Faculty of Biological Sciences we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+; and people with disabilities. Applicants will always be selected based on merit and ability. 

For further information about this scholarship please contact the Faculty Graduate School 

e: [Email Address Removed]


Funding Notes

This scholarship will attract an annual tax-free stipend of £16,062 for up to 3 years, subject to satisfactory academic progress. The award will also cover the academic fees at the UK fee rate. If you are an International fee rated applicant you may still apply, and you will be responsible for funding the difference in academic fees between the UK and International rate (approximately £21,000 per annum). Please provide evidence of this additional funding with your application.

References

Goggolidou, P. & Richards, T. The Genetics of Autosomal Recessive Polycystic Kidney Disease. Biochim Biophys Acta Mol Basis Dis. 2

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