Project supervisors: Dr Christophe Corre - School of Life Sciences / Chemistry
University of Registration: University of Warwick
Non-Academic partner: Dr Nick Allenby - Demuris Ltd, Newcastle
Project title: Rhodococcus bacteria as a source of novel antibiotics
Rhodococcus bacteria are well-known biodegraders of organic pollutants including polychlorinated biphenyls (PCBs) and are widely used in industrial biotechnology processes. However this genus is still very poorly characterised and underexploited.
Since the first genome of a Rhodococcus species became available in 2006, the genomic DNA of 25 Rhodococcus species has been sequenced and deposited in public databases. Bioinformatic analyses of these genomes revealed that everyone of these species has the ability to produce tens of cryptic (unknown) antibiotic-like natural products. For instance the genome of the model organism Rhododoccus RHA1 (9.7 Mb) contains an unexpected 24 non-ribosomal peptide synthetase (NRPS) systems and 7 polyketide synthase (PKS) genes. NRPS and PKS are biosynthetic machineries typically involved in the assembly of antibiotic-like molecules.
This genetic potential is analogous to that of another group of actinomycete bacteria known as Streptomyces which have yielded over 4500 antibiotics, which is approximately two thirds of all those known. Over the last 10 years, advances in genomics and analytical chemistry have renewed academic and industrial interest in antibiotic discovery from such microbial sources. However most of the biosynthetic systems encrypted at the DNA level are typically not expressed in the laboratory environment as they are tightly controlled by transcription factors.
One fundamental aim of our research is to understand how the expression of metabolic pathways for antibiotic production is controlled in these Gram-positive bacteria. We have recently made great advances by discovering and characterising a pathway-specific regulatory system that induces antibiotic production in Streptomyces bacteria. The genomes of Rhodococcus bacteria also contain analogous regulatory systems which we have identified and that, we propose, control the expression of antibiotic-like compounds.
The aim of this project is therefore to understand and exploit pathway-specific regulation in Rhodococcus bacteria to unlock the production of novel antimicrobial compounds.
By combining Dr Corre’s group expertise in pathway-specific microbial regulation and Demuris’ expertise in the discovery of antibiotics from actinomycetes, the specific objectives of the project are: i/ to identify and characterise rhodococci signalling molecules in model Rhodococcus species; ii/ to exploit our understanding of the biological role of these signalling systems in Demuris’ unique biological resources of over 700 Rhodococcus strains; iii/ to isolate and elucidate the structure of newly identified compounds exhibiting antimicrobial activity and to assess their potential as clinically relevant antibiotic drug lead.
Closing date for applications: 8th January 2017
iCASE students must fulfil the MIBTP entry requirements and will join the MIBTP cohort for the taught modules and masterclasses during the first term. iCASE students can then start their PhD project in Jan 2018 but must complete a 3-month miniproject (at a non-home institution) before the end of their first year. They will remain as an integral part of the MIBTP cohort and take part in the core networking activities and transferable skills training. MIBTP iCase.