Nociceptin mediated microvascular inflammation during sepsis

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The University of Sheffield
Faculty of Medicine, Dentistry & Health
Department of Infection and Immunity
Using in vivo imaging in the transparent zebrafish to understand the fate of inflammatory
cells.
Supervisor: Dr Stephen Renshaw and Dr Philip Elks
Project:
Being able to see every inflammatory cell as inflammation proceeds is a uniquely powerful
way to understand this fundamentally important biological process. Using transparent
zebrafish expressing fluorescent proteins in various immune cells, we have pioneered new
ways to see and understand immunity where it counts – in living systems. Using these
systems we have shown how neutrophils are recruited as the body’s first line of defence
against injury and invading pathogens. Once the infectious challenge has been neutralised,
however, it is critical that inflammation resolves and neutrophils are removed, since chronic
inflammation leads to tissue damage and scarring – important in many diseases. Previously,
highly successful PhD students in the lab have shown that resolution of neutrophilic
inflammation can be brought about by a new drug treatment they identified, which causes
neutrophils to migrate away from the inflammatory site, a process known as reverse
migration (Elks et al., 2011 and work in submission). The two most interesting questions
however remain unanswered. In this PhD studentship, the successful candidate will use our
unique approaches to investigate (1) how neutrophil removal from wounds is controlled at
a molecular level and (2) what happens to neutrophils that have reverse migrated away
from wounds. Are reverse migrated neutrophils fully functional? Do they carry with them
some memory of their inflammatory encounter? This is likely to reveal exciting information
of relevance to our understanding and treatment of inflammatory diseases. Students in our
labs are well looked after and have fun, as well as publishing well and getting fantastic
training in cutting-edge microscopy techniques, molecular biology and in vivo modelling.
References:
Elks PM, van Eeden FJ, Dixon G, Wang X, Ingham PW, Whyte MKB, Walmsley SR and
Renshaw SA. Activation of hypoxia-inducible factor-1α (Hif-1α) delays inflammation
resolution by reducing neutrophil apoptosis and reverse migration in a zebrafish
inflammation model. Blood. 2011 Jul 21;118(3):712-22. Epub 2011 May 9.
Entry Requirements:
Candidates must have a first or upper second class honors degree and demonstrate
a passion for cutting edge science, enthusiasm and creativity.
Enquiries:
Interested candidates should in the first instance contact Stephen Renshaw
(s.a.renshaw@sheffield.ac.uk) or Philip Elks (p.elks@sheffield.ac.uk).
How to apply:
Please complete a University Postgraduate Research Application form and attach at
least two references to your application. To complete the application form please
visit: www.shef.ac.uk/postgraduate/research/apply.
Please clearly state the prospective main supervisor in the respective box and select
‘Infection & Immunity’ as the department.
'The Medical School has received a Silver Athena SWAN award
for promoting gender equality’
Website: http://www.sheffield.ac.uk/faculty/medicine-dentistryhealth/graduateschool/prospectivepg/vacancies/ii
Closing date: 3rd February 2014
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