Download Nociceptin mediated microvascular inflammation during sepsis

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
([email protected]) or Stephen Renshaw ([email protected])
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