Cellular senescence: investigating a novel hijack target of the typhoid pathogen Salmonella Typhi

We hypothesise that Salmonella elicits host senescence responses to reprogramme the infection niche through unidentified proteins in the SASP secretome. By identifying the proteins, the project aims to break new ground in an emerging field on pathogen subversion of cellular ageing and use knowledge gained to elucidate diagnostic biomarkers that can help combat the spread of AMR typhoid.
Objective 1: Identify and characterise the Salmonella-induced host cell secretome during infection of cultured human cells.
Objective 2: Validate the host secretome using clinical samples from individuals with acute typhoid at the Queen Elizabeth Central Hospital in Malawi.
The project combines molecular cell biology, infection, proteomic and immunological approaches. By challenging cultured human cells with toxigenic strains of Salmonella, the project will replicate infection mechanisms underlying typhoid. Proteomics will enable identification of 'senescence biomarkers' in the host secretomes and the investigation of their role in infection using a range of human cell-based techniques (objective 1). Field work at the Malawi Liverpool Wellcome Trust Clinical Research Programme will study and validate the host responses using clinical samples from participants with typhoid fever to maximise impact and clinical importance (objective 2).
The studentship takes advantage of a new and exciting collaboration supported by experts in the typhoid field including primary supervisor Dr. Daniel Humphreys (Sheffield) together with co-supervisors Prof. Melita Gordon (Malawi) and Dr. James Meiring (Sheffield). The project aims to contribute to the fight against typhoid and antimicrobial resistance, and improve the health and wealth of vulnerable communities.