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Engineering bacterial therapeutics with enhanced metabolic properties


Project Description

Our understanding of the human gut microbiome is increasing at a rapid pace, to the point where important metabolic interplay between components of the community are now understood. Antibiotic treatment, which selectively removes subset of species from the gut, results in metabolic imbalances of sialic acid and other sugars that can be exploited by important pathogens such as Clostridium difficile and Salmonella enterica to enable colonization. The development of CHAIN Biotech’s Clostridium Assisted Drug Delivery (CADD) platform relies on the delivery and germination of spores in the human gut leading to cell growth enabling the synthesis and delivery of a payload. In this BBSRC iCASE project, we will study the metabolic potential of the species C. butyricum, which includes the CADD organism, through comparative genomic analysis of metabolic pathways and metabolic phenotyping to assess which gut-relevant carbon or nitrogen sources are likely being used for outgrowth in the anaerobic colon and subsequent colonization. The specific energy sources used by the organism are currently unknown, but will likely include monosaccharides, peptides, amino acids and fatty acids. This information can then be used to engineer or evolve strains that might enable prolonged or alternatively reduced residence time of the CADD organism in the gut. Specifically, we will engineer the ability to rapidly uptake and catabolize sialic acid to short chain fatty acids and will then investigate the potential of CADD to deliver this novel metabolic payload to help prevent pathogen colonization post-antibiotic treatment. These experiments will also allow us to learn more about transport and catabolic pathways for sialic acids in the human gut and will use a combination of microbiological, biochemical and bioinformatics techniques used widely in the Thomas lab.

Funding Notes

This is a 4 year fully-funded industrial CASE studentship part of the BBSRC White Rose Doctoral Training Partnership in Mechanistic Biology. The studentship covers: (i) a tax-free stipend at the standard Research Council rate (around £15,000 per year), (ii) tuition fees at UK/EU rate, (iii) research consumables and training necessary for the project. The industrial partner for this project is CHAIN Biotech.

References

Eligibility: The studentships are available to UK and EU students who meet the UK residency requirements. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award. Further information about eligibility for Research Council UK funding

Entry requirements: At least an upper second class honours degree, or equivalent in any biological, chemical, and/or physical science. Students with mathematical backgrounds who are interested in using their skills in addressing biological questions are also welcome to apply.

How good is research at University of York in Biological Sciences?

FTE Category A staff submitted: 44.37

Research output data provided by the Research Excellence Framework (REF)

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