The interaction of bacterial biofilms with immune cells.

Second Supervisor: Miguel Camara/Paul Williams

Project Overview:
P. aeruginosa (PA) is emerging as major opportunistic pathogen of clinical relevance. Acute PA infection is particularly serious in patients suffering from ventilator-associated pneumonia and chemotherapy-associated neutropenia (1,2). PA also causes chronic infection in cystic fibrosis (CF) patients where the lack of effective mucocilliary clearance and intensive antibiotic treatment provides a unique niche for PA to persist leading to the generation of PA strains highly adapted to the CF lung (3). PA causes a resilient infection difficult to eradicate because of the intrinsic resistance of PA to antibiotics, its ability to produce a wide range of virulence factors including toxins, proteases and lipids and form biofilms (3). Biofilms represent a formidable adversary for innate immune cells responsible for bacterial clearance, macrophages and neutrophils and can lead to the induction of chronic inflammation (4). To better understand the ability of biofilms to modulate the inflammatory response, this project aims to study the interaction of PA biofilms with human immune cells. We will determine how biofilms modulate the activation of human macrophages, dendritic cells and neutrophils by assessing cell survival (5), cytokine production, ability to activate and differentiate T cells, and formation of extracellular nets.
This project builds upon an ongoing research project funded by the MRC to Dr Martinez-Pomares and Profs Miguel Camara and Paul Williams. The student will acquire experience in the generation and characterisation of PA biofilms, purification and culture of primary human immune cells, flow cytometry, confocal and live microscopy, cytokine quantification, carbohydrate and protein purification, SDS-PAGE, Western blotting, molecular biology, qPCR.

The University of Nottingham is one of the world’s most respected research-intensive universities, ranked 8th in the UK for research power (REF 2014). Students studying in the School of Life Sciences will have the opportunity to thrive in a vibrant, multidisciplinary environment, with expert supervision from leaders in their field, state-of-the-art facilities and strong links with industry. Students are closely monitored in terms of their personal and professional progression throughout their study period and are assigned academic mentors in addition to their supervisory team. The School provides structured training as a fundamental part of postgraduate personal development and our training programme enables students to develop skills across the four domains of the Vitae Researcher Development Framework (RDF). During their studies, students will also have the opportunity to attend and present at conferences around the world. The School puts strong emphasis on the promotion of postgraduate research with a 2-day annual PhD research symposium attended by all students, plus academic staff and invited speakers.