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Research Associate
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Research Associate
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Research Associate
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Research Associate
6 months ago
Applications are invited for a Research Associate role funded by both UKRI and an industry award. You will work on a multi-component research effort project aimed at developing a number of cell-based systems for drug discovery and testing, alongside work investigating the mechanism of action of the typhoid toxin of Salmonella Typhi, with the long-term aim of combatting drug-resistant typhoid and chronic carriage in humans. The project aims to contribute to the fight against typhoid and antimicrobial resistance, and improve the health and wealth of vulnerable communities.
Salmonella Typhi is a major pathogen in the global fight against antimicrobial resistance. Increasing rates of multi
- and extensively drug-resistant typhoid are found among the ~27 million cases each year. A critical barrier to controlling typhoid and antimicrobial-resistance is chronic Salmonella carriage, which refers to chronically-infected individuals who contaminate the food-chain with S. Typhi and drive transmission. Understanding how chronic infection develops, and identifying effective diagnostic, treatment and prevention strategies to detect carriers is vital to typhoid elimination efforts.
A major virulence factor implicated in chronic carriage is the typhoid toxin of S.Typhi. In a recent Nature Communications article (doi: 10.1038/s41467-019-12064-1), we discovered that the toxin induces a peculiar form of DNA damage in human cells - the RING phenotype - which hijacks DNA repair machines. We found that the RING phenotype accelerates an ageing-like process called senescence, which drives Salmonella infection. These data suggest a mechanism by which the typhoid toxin induces senescence to establish chronic carriage.
The successful applicant will join Dr. Daniel Humphreys and Prof Carl Smythe at the School of Biosciences to establish cell based systems for drug discovery and to investigate DNA damage responses in clinical samples from human participants infected with Salmonella Typhi. Findings will be investigated using cultured human cells, which will be infected with Salmonella Typhi.
Applicants must have a good honours degree and PhD in a relevant biological discipline (or equivalent experience) along with experience in a range of biochemical, molecular biology and in vitro cell culture approaches. Significant experience with molecular techniques, including qRT-PCR, western blotting and ELISA and proficiency in microscopy techniques with experience using confocal and Widefield microscope are also essential.
Salmonella Typhi will be studied within a high-security containment level 3 laboratory (CL3) at the University of Sheffield. To work with Salmonella Typhi, the applicant will need to be vaccinated against typhoid fever, bacterial meningitis and hepatitis B (i.e. experimental pathogens in the CL3) to gain a HM 50d: Fitness for Special Projects Certificate and start the project. It is desirable that applicants have experience in studying typhoid, host-pathogen interactions, analysing large data sets, DNA damage and senescence (a PhD is essential) in addition to associated functional assays including qPCR, immuno-cytochemistry, cytotoxicity, and viability assays.
We’re one of the best not-for-profit organisations to work for in the UK. The University’s Total Reward Package includes a competitive salary, a generous Pension Scheme and annual leave entitlement, as well as access to a range of learning and development courses to support your personal and professional development.
We build teams of people from different heritages and lifestyles from across the world, whose talent and contributions complement each other to greatest effect. We believe diversity in all its forms delivers greater impact through research, teaching and student experience.
