A novel family of type VI-secreted toxins subverting macrophages

*FUNDING CONFIRMED*

Successful pathogens overcome innate immune barriers such as macrophages, which engulf and trap bacteria in membrane-bound vesicles. Engulfed pathogens disarm macrophages and counteract immunity by deploying proteins (effectors) that subvert key cellular pathways. The host cell cytoskeleton’s plays a critical role in both detection of bacterial pathogens and mobilization of antibacterial responses. Not surprisingly, pathogen-induced disorganization of the actin network is a remarkable anti-host strategy. The actin network in the context of chronic diseases that impair macrophage functions (e.g. cystic fibrosis, diabetes, chronic obstructive pulmonary disease) has not been extensively explored. We discovered that cystic fibrosis (CF) gene-defective macrophages fail to clear engulfed bacteria and play a central role in maintaining the chronic inflammation state associated with disease.

We will use the intracellular opportunistic CF pathogen Burkholderia cenocepacia, which carries a type VI- secretion system (T6SS-Bc) that disrupts the actin network and elicits exaggerated proinflammatory responses. These phenotypes depend on TecA, a novel toxin that inactivates Rho GTPases. We will address 3 questions: (i) How TecA is secreted by the T6SS-Bc?
(ii) How defective actin polymerization is sensed by the inflammasome? and (iii) What is the status of the inflammasome in B. cenocepacia infected CF gene-defective human peripheral monocytes? Understanding how pathogens modulate the macrophages’ actin network to drive inflammation will enable the discovery of new checkpoints for controlling dysregulated inflammation secondary to bacterial infection.

REQUIREMENTS

Candidates should have or expect to obtain a 2:1 or higher Honours degree or equivalent in a relevant biomedical or life sciences subject.

English Language

Candidates applying from countries where the first language is not English should produce evidence of their competence through a qualification such as IELTS or TOEFL score.

The minimum recommended score for the School of Medicine, Dentistry and Biomedical Science is:
• IELTS score of 6.0 with not less than 5.5 in each of the four component elements of listening, reading, speaking and writing taken within the last 2 years;
• TOEFL score of 80+ (internet basted test), taken within the last 2 years, with minimum component scores of; Listening 17, Reading 18, Speaking 20, Writing 17);
• A valid Certificate of Proficiency in English grade A or B;
• A valid Certificate of Advanced English grade A; or
• A first or upper second class honours degree from a university based in the UK, Republic of Ireland or other suitably quality assured location in a country deemed by the UK Border Agency to be majority English speaking.

For a list of English Language qualifications also accepted by the School and University please see the following link:
http://www.qub.ac.uk/International/International-students/Applying/English-language-requirements/

The English Language Unit (ELU) offers both pre-sessional and in-sessional courses in English for academic purposes and study skills. Courses vary in length and full information can be obtained from the ELU http://www.qub.ac.uk/tefl/