The University of Sheffield

Faculty of Medicine, Dentistry & Health

Department of Infection and Immunity

Inflammation and Infection; competing two immune cell stimuli in the transparent zebrafish model

Supervisor: Dr Philip Elks and Dr Stephen Renshaw

Project:

Immune cells are constantly patrolling the body, ready to react to injury or infection when required. Their activity must be tightly controlled by cell signalling pathways in order that they don’t become activated inappropriately leading to damage and scarring to surrounding, healthy, tissues. We have uncovered an immune cell activating role for a genetic signalling pathway involved in oxygen sensing, Hif signalling, in a zebrafish model. Zebrafish embryos are transparent and uniquely allow us to follow the behaviour of fluorescently labelled immune cells in the whole, in vivo, organism. We have previously demonstrated that activating neutrophils with Hif signalling helps the zebrafish fight a bacterial infection by increasing aspects of their immune activity (Elks et al., in press). Conversely, during inflammation, increased Hif leads to an over-activated neutrophil response leading to persisting inflammation, a process detrimental to the body (Elks et al., 2011). Hif represents a potentially exciting, novel therapeutic target for both infection and inflammation, however more needs to be understood about how these processes are regulated before drugs targeting Hif can be considered for human use. Using the unique opportunities the zebrafish model allows the successful candidate will investigate how immune cells behave when zebrafish are exposed to both infection and inflammation signals in the context of Hif. Do immune cells preferentially tackle infection over inflammation, or does the inflammation response take precedence over the immune cells leading to wider-spread, uncontrolled, infection? What happens to these responses when these immune cells are activated using Hif signalling? Using cutting edge microscopy and molecular biology techniques the successful candidate will investigate these questions in a highly successful and social lab.

References:

Elks PM, Brizee S, van der Vaart M, Walmsley SR, van Eeden FJ, Renshaw SA and Meijer AM. Stabilisation of hypoxia inducible factor-1α (Hif-1α) decreases bacterial burden of Mycobacterium marinum infection in an inducible nitric oxide synthase (iNOS) dependent mechanism. In press, Plos Pathogens

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 Philip Elks () or Stephen Renshaw ()

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-dentistry-health/graduateschool/prospectivepg/vacancies/ii

Closing date: 3rd February 2014