Research Fellow, Centre for Experimental Medicine
Application closing date 01/07/2019
Salary £33,199 - £34,189 per annum
Job category/type Research
Queen's University Belfast is one of the leading universities in the UK and Ireland, with a distinguished heritage and history. With over 24,000 students, 3,700 staff and an annual turnover of some GBP 300m, Queen's University Belfast plays a unique leadership role in Northern Ireland. As a member of the Russell Group of UK research-intensive universities, Queen's University Belfast combines excellence in research and education with a student centred ethos.
The Centre for Experimental Medicine is an interdisciplinary research centre which is committed to the highest quality scientific endeavour, with over 250 basic and clinical scientists working on site. Our mission is to understand the mechanisms of disease and use that understanding to develop innovative new treatments and therapies to improve patient outcomes.
A Postdoctoral Research Fellow position for a PhD with training and demonstrated abilities in cell biology/cellularimmunology/cellular microbiology is available in the Valvano group to investigate the inflammasome in human CFTR-defective macrophages and monocytes.
Infection and chronic inflammation in patients with cystic fibrosis (CF) lead to progressive lung damage. CF-defective macrophages fail to kill engulfed opportunistic pathogens such as Burkholderia cenocepacia. Engulfed pathogens disarm macrophages and counteract immunity by deploying proteins (effectors) that alter central cellular pathways including actin cytoskeleton remodelling. Pathogen-induced disorganization of the actin cytoskeleton is both a remarkable anti-host strategy and a danger signal driving inflammation and cell death. However, the actin cytoskeleton dynamics in the context of the CF defect has not been explored. We hypothesize that intracellular opportunistic pathogens engulfed by macrophages, in combination with the CF genetic defect, induce disorganization of the actin cytoskeleton that leads to a highly proinflammatory state. Our research established B. cenocepacia as a model organism for cellularmicrobiology. We discovered that a B. cenocepacia type VI-secretion system(T6SS) disrupts the macrophage's actin cytoskeleton and elicits pyroptosis (proinflammatory cell death), and we recently identified TecA as the T6SSprotein responsible for these phenotypes by causing the direct inactivation ofRho GTPases, which in turn activates the Pyrin inflammasome and the ASC complexformation. We will investigate here the relationship between inflammation andB. cenocepacia-mediated modulation of macrophages' actin cytoskeleton inCFTR-defective human monocytic macrophages. We will address 2 specific aims:(1) To assess the status of the pyrin inflammasome in B. cenocepacia-infected,CFTR-defective peripheral monocytes; and (2) To evaluate the role of the B.cenocepacia T4SS and T2SS systems in the activation of ASC-dependent inflammasomes upon infection in human macrophages.
The successful candidate will work in partnership with members of the Valvano group, plan and perform experiment and will also be involved supervision and training of junior lab members.
This post is available for 12 months initially.
For further information contact Dr Julia Monjaras Feria: J.MonjarasFeria@qub.ac.uk
Further information on the Lab can be found via the link below: http://publish.uwo.ca/-mvalvano/