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Investigating host-microbial crosstalk, immunity and tissue repair at the intestinal barrier

  • Full or part time
  • Application Deadline
    Sunday, December 01, 2019
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Fully funded 3.5 year PhD programme available in the lab of Dr. Chris Schiering at the London Institute of Medical Sciences. This position provides the opportunity to undertake a PhD project in a highly dynamic, scientifically stimulating and interactive research environment and will enable you to make novel contributions to scientific knowledge and understanding.

Our group studies the gastrointestinal tract with a particular focus on host-microbiota interactions, tissue homeostasis and barrier immunity. Environmental factors, such as diet and intestinal microbiota, are important modulators of intestinal physiology yet little is known about how these cues are integrated at the cellular and molecular level. We investigate the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor capable of sensing dietary components and microbial metabolites. We and others have demonstrated that genetic deficiency in AHR is associated with compromised intestinal barrier integrity, altered microbiota composition and dysregulated host responses to pathogens and injury. Importantly, genome-wide association studies have identified AHR as susceptibility locus in inflammatory bowel disease, highlighting the relevance of this pathway to human disease.

The aim of this project is to explore the complexity and function of newly discovered AHR-dependent cell-types in the gastrointestinal tract using a variety of approaches. Firstly, you will gain experience with in vivo models of enteric infection, intestinal tissue injury and metabolic disease. Secondly, you will use single cell RNA-sequencing to generate high-resolution AHR-responsive cellular networks of distinct intestinal compartments and disease states. Thirdly, you will perform genome-wide mapping of AHR binding sites by ChIP-seq on specific cell-types within their native tissue microenvironment. Finally, you will become proficient in multiparameter flow cytometry, confocal microscopy as well as standard molecular biology techniques.

Together, your findings will provide important insights into the regulation of intestinal physiology by AHR and may facilitate the discovery of novel therapeutics for the treatment of chronic inflammatory diseases.

Skills covered in this project:

• RNA-seq, ChIP-seq, single cell RNA-seq,
• Multiparameter flow cytometry
• Confocal microscopy
• Enteric infection models
• Intestinal injury and repair models
• Cell culture and molecular biology techniques


Feel free to contact Chris directly with questions about the project: or

To Apply: Please visit our website (https://lms.mrc.ac.uk/study-here/phd-studentships/lms-3-5yr-studentships/) to download an application form.

Funding Notes

This project is one of multiple available projects potentially funded by the MRC. If successful the studentship would cover all tuition fee payments and includes a tax-free stipend amounting to £21,000pa (paid in monthly installments directly to the student) for 3.5 years.

Whilst this funding is available to students worldwide, due to the higher tuition fee rate of overseas students competition is higher and so only exceptional OS applicants will be considered.

References

Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, Omenetti S, Henderson CJ, Wolf CR, Nebert DW, Stockinger B. (2017). Feedback control of AHR signalling regulates intestinal immunity. Nature 542: 242-5

Schiering C, Krausgruber T, Chomka A, Frohlich A, Adelmann K, Wohlfert EA, Pott J, Griseri T, Bollrath J, Hegazy AN, Harrison OJ, Owens BM, Lohning M, Belkaid Y, Fallon PG, Powrie F. (2014). The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature 513: 564-8

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