Uncontrolled inflammation is known to be a major driver of pathology in many common disabling diseases, including common and debilitating lung diseases such as Chronic Obstructive Pulmonary Disease (COPD), which causes over 3 million deaths globally each year (WHO). There is a pressing need for pro-resolution therapies that target persisting inflammatory neutrophils, while leaving circulating neutrophils able to respond to infectious threats. We seek to determine the molecular mechanisms behind regulation of neutrophil function and to identify drug targets to develop their translational potential.
Although neutrophils are resistant to the anti-inflammatory effects of current treatments, our lab has shown that targeting neutrophil phenotype can drive inflammation resolution. Gene transcription, through regulation of RNA stability, is important in controlling neutrophil phenotype. We have shown that the RNA stabilising protein, ELAVL1, controls the inflammatory phenotype of the neutrophil by regulating expression of pro-inflammatory gene products. You will use in vivo (zebrafish) and in vitro (human neutrophils) models to manipulate neutrophil phenotype to reveal the downstream targets of ELAVL1, identifying new drug targets for the treatment of inflammatory disease.
Zebrafish are an excellent model for in vivo studies of neutrophil function, since their genes are easily manipulated, which allows the genes controlling neutrophil recruitment and resolution of inflammation to be identified. Using our model of tailfin transection, we can visualise the behavioural dynamics of neutrophils at wound sites in several transgenic zebrafish lines and various live stains.
Ours is a lively, fun and exciting lab to work in. There are lots of post-docs around to help. We strongly encourage students attendance international conferences, and we operate a publication-focussed lab culture that allows students to publish manuscripts at an early stage.
Please note, this project is also being advertised under China Scholarship Council scheme.
Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience.
How to apply:
Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying
Please clearly state the prospective main supervisor in the respective box and select 'Infection, Immunity and Cardiovascular Disease' as the department.
Enquiries:
Interested candidates should in the first instance contact Prof Steve Renshaw, [Email Address Removed]
Closing date - Wednesday 26th January 2022 at 5pm.
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