Location: | London |
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Salary: | £43,205 per annum, including London Weighting Allowance. |
Hours: | Full Time |
Contract Type: | Fixed-Term/Contract |
Placed On: | 12th March 2024 |
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Closes: | 26th March 2024 |
Job Ref: | 085873 |
Job Description
The Odendall Laboratory studies both sides of interactions between the host and enteric bacterial pathogens. We seek to understand the interplay between the bacteria Salmonella and Shigella and type I and III interferons (IFNs).
Type I and III IFNs are induced, along with other cytokines, upon detection of microbes. They have a direct effect on the tissue, inducing hundreds of interferon-stimulated genes (ISGs), with diverse antimicrobial functions. While the functions of type I/III IFNs in antiviral immunity are extensively studied, if/how IFNs and their ISGs protect against bacterial infection is poorly understood.
We have recently reported that bacterial factors translocated by the Shigella type III secretion system (T3SS) block IFN receptor signalling (Alphonse et al, Cell, 2022), and the induction if ISGs. This suggests the importance of this pathway in host defence against bacteria. Indeed, IFNs were protective against Shigella infection in cellular and animal models of infection.
Similarly, we have found that IFN restricted intracellular infection with Salmonella, an enteric pathogen with similarities with Shigella. In particular, IFN affected the subcellular localisation of Salmonella, preventing its access to the cytosol, where the bacteria normally replicate. Through an ISG screen, we identified a few key host proteins that may directly mediate the effects of IFN in epithelial cells. Additionally, preliminary screens have revealed that Salmonella may have also evolved effectors that target IFN signalling pathways.
This exciting MRC-funded project will determine the molecular mechanisms through which IFNs and their ISGs affects the Salmonella intracellular lifecycle in cellular models of infection. The stability of the Salmonella containing vacuole will be visualised by live cell imaging. The transcriptome of cytosolic and vacuolar bacteria will be analysed in the presence or absence of IFN via RNA sequencing.
The successful candidate will have a PhD in microbiology, cellular biology, cellular microbiology or immunology. They will be hardworking with a proven track record of publication as a primary author of scientific paper(s) in well-regarded scientific journals, and have a particular interest in tackling fundamental questions regarding host-pathogen interactions.
This post will be offered on an a fixed-term contract until February 2026.
This is a full-time post.
Skills, knowledge, and experience
Extensive experience in microscopy will be required. Experience in innate immunity or cellular microbiology will be desirable but not required.
Essential criteria
Desirable criteria
* Please note that this is a PhD level role but candidates who have submitted their thesis and are awaiting award of their PhDs will be considered. In these circumstances the appointment will be made at Grade 5, spine point 30 with the title of Research Assistant. Upon confirmation of the award of the PhD, the job title will become Research Associate and the salary will increase to Grade 6.
Further Information
Informal inquiries are strongly encouraged. Please do not hesitate to contact Dr Charlotte Odendall (charlotte.odendall@kcl.ac.uk) for further details.
Closing date: 26th March 2024
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