Phase variable epigenetic control of strain fitness of starter cultures and probiotics

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 Horsholm 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 Horsholm 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