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Structural and functional studies on proteins required for vision

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  • Full or part time
    Dr J.J.B. Cockburn
    Prof Colin Johnson
    Prof N A Ranson
  • 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

Rod and cone cells in the retina detect light using an elaborate photoreceptor, allowing us to see. Development and maintenance of the photoreceptor outer segment requires proteins located at its base that form a specialized structure called the connecting cilium. Mutations in these proteins are a major cause of childhood and adult-onset blindness.

Working jointly between the Cockburn, Johnson and Ranson groups at the University of Leeds, you will use the latest cutting-edge structural biology and imaging techniques (X-ray crystallography, cryo-EM, super-resolution imaging, soft X-ray tomography, correlative light and electron microscopy) to solve structures of connecting cilium proteins and their complexes, and place these structures into the cellular context. This will provide the first molecular-level insights into the connecting cilium architecture, which will be essential to realize the full therapeutic potential of gene therapies and drugs to treat hereditary blindness and other inherited disorders associated with ciliary dysfunction.

The Astbury Centre for Structural Molecular Biology brings together over 60 research groups across the University of Leeds, from biological sciences, physics and chemistry, who work towards understanding the molecular basis of living processes. The Centre is a major hub for structural biology in the UK, with world-class facilities and a vibrant, highly interdisciplinary research environment.

Funding Notes

White Rose BBSRC Doctoral Training Partnership in Mechanistic Biology
4 year fully-funded programme of integrated research and skills training, starting Oct 2019:
• Research Council Stipend
• UK/EU Tuition Fees
• Conference allowance
• Research Costs

Requirements:
At least a 2:1 honours degree or equivalent. We welcome students with backgrounds in biological, chemical or physical sciences, or mathematical backgrounds with an interest in biological questions.
EU candidates require 3 years of UK residency in order to receive full studentship

Not all projects advertised will be funded; the DTP will appoint a limited number of candidates via a competitive process.

https://biologicalsciences.leeds.ac.uk/directory/research-opportunities

References

Cockburn JJB, Hesketh SJ, Mulhair P, Thomsen M, O’Connell MJ, Way M. Insights into kinesin-1 activation from the crystal structure of KLC2 bound to JIP3. Structure 2018 Nov 6;26:1-13. https://doi.org/10.1016/j.str.2018.07.011).

Hesketh EL, Meshcheriakova Y, Dent KC, Saxena P, Thompson RF, Cockburn JJ, Lomonossoff GP, Ranson NA. Mechanisms of assembly and genome packaging in an RNA virus revealed by high-resolution cryo-EM. Nat Commun. 2015 Dec 10;6:10113. doi: 10.1038/ncomms10113.

Buskin A*, Zhu L*, Chichagova V*, Basu B*, Mozaffari-Jovin S*, …34 others… Grellscheid S-N+, Johnson CA+, Lako M+ (2018). Disrupted alternative splicing for genes implicated in splicing and ciliogenesis causes PRPF31 retinitis pigmentosa. Nat Commun in press

Wheway G*, Schmidts M*, Mans DA*, Szymanska K*, Nguyen T-MT*, ...69 others... Doherty D+, Mitchison HM+, Roepman R+, Johnson CA+ (2015). An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes. Nat. Cell. Biol. 17: 1074-87

(* joint first authors, + joint corresponding authors)

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

Research output data provided by the Research Excellence Framework (REF)

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