A Postdoctoral Research Fellow position for a PhD withtraining and demonstrated abilities in cell biology/cellularimmunology/cellular microbiology is available in the Valvano group toinvestigate the inflammasome in human CFTR-defective macrophages and monocytes.
Infection and chronicinflammation in patients with cystic fibrosis (CF) lead to progressive lungdamage. CF-defective macrophages fail to kill engulfed opportunistic pathogenssuch as Burkholderia cenocepacia. Engulfed pathogens disarm macrophages andcounteract immunity by deploying proteins (effectors) that alter centralcellular pathways including actin cytoskeleton remodelling. Pathogen-induceddisorganization of the actin cytoskeleton is both a remarkable anti-hoststrategy and a danger signal driving inflammation and cell death. However, theactin cytoskeleton dynamics in the context of the CF defect has not been explored. We hypothesize that intracellular opportunistic pathogens engulfed bymacrophages, in combination with the CF genetic defect, induce disorganizationof the actin cytoskeleton that leads to a highly proinflammatory state. Ourresearch 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-dependentinflammasomes 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