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KTN CASE BBSRC studentship: Phase variable epigenetic control of strain fitness of starter cultures and probiotics

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  • Full or part time
    Prof Marco Rinaldo Oggioni
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (UK Students Only)
    Funded PhD Project (UK Students Only)

Project Description

Preamble: This is an interdisciplinary KTN CASE BBSRC PhD project supervised jointly by two academic supervisors from the Department of Genetics (Marco R Oggioni) and Mathematics (Andrew Morozov) of the University of Leicester UK and by two industrial supervisors at Chr. Hansen A/S in Hørsholm Denmark (Ana Rute Neves and Jonas Jacobsen). The student will be based at Leicester, but during the four years the student will be hosted for six months at the Chr. Hansen headquarters and research facility at Hørsholm in Denmark.

Background: Phase variable type I restriction modification (R-M) systems have been identified and we have shown that they provide a novel bacterial epigenetic control mechanism that affects both gene expression and important bacterial phenotypes; i.e. in pathogens, these systems were linked to the capacity for generating disease (Manso et al., Nature Communications 2014). The phase variable genetic modules are based on repeated inverted copies of the specificity gene (hsdS) of the R-M system that allows for high frequency recombination conferring the R-M system with multiple different methylation target specificities. These double-hsdS modules are widespread among firmicutes, including bacterial species of industrial relevance for the production of starter cultures or for use as probiotic functional foods. Extensive genomic data is now available, both for bacterial strains already utilised by industry and for strains being screened for their commercial potential. The proposed project will combine the academic partner’s expertise gained by studying the phase variable double-hsdS modules in the lactic acid bacterium Streptococcus pneumoniae (Manso et al., Nature Communications 2014) with the vast expertise in bacterial strain phenotyping at Chr. Hansen (Derkx et al., Microb Cell Fact. 2014) and the large number of sequenced genomes available through the industrial partner.

Aims and objectives: The primary aim of the project is to characterise phase variable double-hsdS modules in firmicutes of commercial interest, especially lactobacilli, and to evaluate their impact on strain fitness and metabolic potential. The long term goal of the whole project would be to produce high level scientific data to allow optimisation of quality control and product efficacy of industrially relevant bacteria harbouring these phase variable epigenetic control systems. To reach this aim the project will be structured around a series of objectives which include:
-Genomic characterisation of phase variable double-hsdS modules.
-Design of double-hsdS allele quantification protocols.
-Phenotypic profiling of sub-clones enriched for a single hsdS allele.
-Evaluation of the epigenetic impact of variations in double-hsdS modules.
-Mathematical modelling of recombination and impact.
-Transfer of the scientific insight to the management of starter cultures and quality control protocols.

Training:
At the University of Leicester the project will provide the student with high quality research training while working in an interdisciplinary team. The methodologies will include bacterial phenotyping, utilisation of multiple “omic” technologies, including genome mining, RNAseq, methylome analysis and metabolomics. The project will have a mathematical component aimed at modelling of phase variable traits. At UOL the student will be in addition be trained in running experimental infection models after having obtained a personal licence. The PhD student on this project will in addition attend the courses on Linux, High Performance Computing to be able to analyse sequence data on bioinformatics software suites running on high performance computing clusters. At Chr. Hansen the student will be hosted at the Dept. of Bacterial Physiology and Improvement and be involved in strain phenotyping and at the Dept. of Fermentation to test observed phenotypes in real world conditions. The variety of research and product development activities ongoing at Chr. Hansen will provide the student with an excellent example of industry lead research and product development, and is expected to increase his/her competitiveness in future career endeavours. In addition to this academic training and the industrial secondment, there will be dedicated training days for the students organised by KTN.

Funding Notes

This is a KTN CASE BBSRC studentship funded through the Knowledge Transfer Network of Innovate UK. The salary of KTN CASE students is slightly higher than for normal PhD fellowships and the expenses of the six month placement abroad are covered by a specific additional budget.
The project requires the student to carry out experimental infections and to obtain a personal licence from the home office. The project importantly requires two periods of placement of about 3 month each in Hørsholm Denmark at the Research facilities of Chr. Hansen.

The interview is expected to be in the week of 25/01/2016.

References

Manso AS, Chai MH, Atack JM, Furi L, De Ste Croix M, Haigh R, Trappetti C, Ogunniyi AD, Shewell LK, Boitano M, Clark TA, Korlach J, Blades M, Mirkes E, Gorban AN, Paton JC, Jennings MP, Oggioni MR. A random six-phase switch regulates pneumococcal virulence via global epigenetic changes. Nat Commun. 2014 Sep 30;5:5055.

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