The University of Sheffield
Faculty of Medicine, Dentistry & Health
Department of Infection and Immunity
INVESTIGATING CONTROL OF MACROPHAGE FUNCTION BY CLEARANCE OF
APOPTOTIC CELLS USING DROSOPHILA MELANOGASTER
Supervisor: Dr Iwan Evans
Project:
Inappropriate immune cell responses cause or exacerbate a wide range of human diseases including
autoimmunity, atherosclerosis, cancer and chronic inflammatory conditions. An important function
of the white blood cells known as macrophages is to remove and degrade cells undergoing
programmed cell death (apoptosis). This process can suppress pro-inflammatory responses of
macrophages and is linked to the resolution of inflammation.
Fruit flies (Drosophila melanogaster) contain a population of highly migratory macrophages, called
hemocytes. The genetic tractability and unparalleled live imaging possibilities of this system
enables us to study the cell biology of apoptotic cell clearance by macrophages in vivo. This project
will study how clearance of apoptotic cells affects the subsequent behaviour of macrophages, with a
strong focus on regulation of their motility and inflammatory responses. We will also characterise
how interactions between apoptotic cells and macrophages influences signalling and phenotype
within the latter in order to understand how apoptotic cells can dampen inflammatory responses in
vivo. Tissue culture approaches will also be used to test the relevance of mechanistic findings to
mammalian macrophages.
This project is ideal for a candidate with strong interests in cell biology and the use of model
organisms to study human disease-relevant questions in vivo. Knowledge of cell migration is
desirable, but an enthusiasm for science and an enquiring mind is far more important. No prior
knowledge of Drosophila is required, since the successful candidate will be given intensive training
in the use of Drosophila as a genetic platform to study cell biology in vivo. This will involve a
significant amount of dynamic imaging of macrophage behaviour in vivo using confocal
microscopy, alongside standard cell biological techniques such as whole mount immunostaining
and in situ hybridisation.
For further information see:
I. Evans, P. Ghai, V. Urbancic, K.-L. Tan and W. Wood (2013). SCAR/WAVE-mediated
processing of engulfed apoptotic corpses is essential for effective macrophage migration in
Drosophila. Cell Death and Differentiation. 20(5):709-20.
I. Evans, W. Razzell, P. Martin and W. Wood (2013). Calcium flashes orchestrate the wound
inflammatory response through DUOX activation and hydrogen peroxide release. Curr Biol.
23(5):424-9.
I. Evans and W. Wood (2011). Drosophila embryonic hemocytes. Curr Biol. 21(5):R173-4.
Evans lab website
Entry Requirements:
Candidates must have a first or upper second class honours degree or significant
research experience.
Enquiries:
Interested
candidates
should
in
the
first
instance
contact
Iwan
Evans
(i.r.evans@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.
Website: http://www.sheffield.ac.uk/faculty/medicine-dentistryhealth/graduateschool/prospectivepg/vacancies/ii
Closing date: To be agreed