Our research in fundamental and applied disease-related mechanistic microbiology has resulted both in novel therapeutic drug leads and in cancer gene therapy approaches.
Passing on genes in the third domain of life: all organisms need to ensure that their offspring inherit a complete set of genes. To achieve this, cells must not only copy their DNA but the two copies must also be segregated accurately as a cell divides to ensure that each daughter cell has a complete copy of the genetic code. Much is known about how this DNA segregation occurs in organisms such as ourselves and in bacteria. However, little is known about how this critical process occurs in the third domain of life, the archaea. Daniela Barillà’s team here in York, in collaboration with Maria Schumacher at Duke University, USA, has revealed the machinery that performs this function in archaea. Surprisingly, this archaeal system combines components found in bacteria with those found in organisms such as ourselves, suggesting the principles of DNA segregation are conserved across all three domains of life.
Generating new antimicrobials by combining different antibiotic biosynthesis pathways: antibiotics revolutionised medicine in the 20th century but the increasing prevalence of resistant bacteria now presents a major threat. There is therefore a need for novel antibiotics to combat these resistant bacteria. One approach to generating new antibiotics is to use genes from two different antibiotic pathways to form a novel antimicrobial compound. A team led by Maggie Smith in York, in collaboration with Isomerase Therapeutics in Cambridge, has created a suite of new genetic tools to make it much easier to exploit genes from two different antibiotic biosynthesis pathways. These genetic tools will greatly accelerate our ability to test antibiotic biosynthesis genes in a variety of combinations to see whether they can generate a new antibiotic.
Dr Daniela Barillà, Senior Lecturer: the molecular mechanisms and dynamics of prokaryotic DNA segregation, partition cassettes in bacteria and archaea.
Professor Michael Brockhurst, Anniversary Chair: the effects of rapid contemporary evolution in microbes.
Professor Neil C Bruce, Professor of Biotechnology: microbial metabolism; biocatalysis and environmental biotechnology; understanding how microorganisms utilise xenobiotic compounds for growth.
Dr James Chong, Senior Lecturer: DNA replication and cellular proliferation in methanogenic archaea; molecular mechanisms of replicative helicases; microbial population dynamics in anaerobic digestion.
Dr Julia Ferrari, Lecturer: how symbionts affect their hosts’ ecology; the interaction and co-evolution of multiple partners in these systems.
Professor Alastair H Fitter, CBE, FRS: plant and microbial behaviour in a changing world; below ground ecology and functional ecology of roots and mycorrhizal symbioses; carbon cycling in soil especially in relation to mycorrhizas.
Dr Paul Fogg, Sir Henry Dale Fellow, The impact of mobile genetic elements on bacterial evolution; The role of gene transfer agents (GTAs) in the spread of antibiotic resistance and virulence genes; Fundamental mechanisms of GTA activity; Applications of bacteriophages and bacteriophage-derived proteins.
Dr Ville Friman, Lecturer in Evolutionary Biology: Experimental evolution, Predator-prey interactions, Host-parasite interactions, coevolution, virulence, competition cooperation, community ecology, trade-offs, eco-evolutionary dynamics, antibiotic resistance, ecosystem functioning, phage therapy, rhizobiomes
Dr Thorunn Helgason, Lecturer: the role of arbuscular mycorrhizal fungi as a conduit for mineral nutrients between plants and soil.
Dr Angela Hodge, Reader: plant-soil-microbe interactions; mycorrhizal fungi and nutrient cycling in soil systems using mechanistic and ecological approaches.
Professor Norman J Maitland, Director of the YCR Cancer Research Unit: novel biotherapies for prostate cancer based on targeted and stealthed viral vectors; engineering of tumour-specific viruses (oncolytics).
Professor Jeremy Mottram, Chair of Pathogen Biology: Leishmania, African trypanosomes, parasite genetic manipulation, macrophages, peptidases,protein kinases.
Fabiola Martin, Senior Clinical Lecturer in HIV medicine: prevention of mother to child transmission of HIV; the natural history and management of HTLV-1 associated myelopathy.
Professor Peter McGlynn, Reader: the causes and consequences of malfunctions in the complex protein machines that copy DNA; the repair of broken DNA replication machines to minimise corruption of the genetic code.
Dr James W B Moir, Reader: understanding the organisation and regulation of metabolic processes (particularly respiration) in pathogenic Neisseria species; how microbial metabolism influences the function of microbial communities in the human body.
Professor Jennifer R Potts, Professor of Molecular Biophysics: mechanisms of host-pathogen interactions that play an important role in the maintenance and dissemination of infection.
Professor Deborah F Smith, OBE: novel therapeutic targets against the causative agents of human leishmaniasis; genetic, cellular and biochemical studies of Trypanosoma brucei, the causative agent of African sleeping sickness.
Professor Maggie Smith: adaptations of phages that infect the antibiotic-producing, mycelial bacteria, Streptomyces; phage integrases as tools for DNA integration and assembly in microbes, plants and animals; evolution of phage genomes and the diversity of phage defence systems in bacteria.
Dr Gavin H Thomas, Reader: mechanisms used by pathogenic bacteria to utilise host-derived sialic acid; constraint-based modelling of obligate symbiosis between bacteria and insect hosts such as Buchnera aphidicola and aphids.
Dr Marjan van der Woude, Reader: bacterial adaptions to exploit local environmental conditions; heritable (epigenetic) gene regulation via DNA methylation and phase variation; the relevance of these processes to bacterial pathogenesis and biofilm formation.
Professor J Peter W Young: population genetics, molecular phylogeny and comparative genomics of rhizobia and other bacteria; molecular ecology and diversity of mycorrhizal fungi.
Temperate phages both mediate and drive adaptive evolution in pathogen biofilms. Brockhurst et al. 2016 PNAS
Multiplexed Integrating Plasmids for Engineering of the Erythromycin Gene Cluster for Expression in Streptomyces spp. and Combinatorial Biosynthesis. Smith et al. 2015 Applied and Environmental Biology
Structures of archaeal DNA segregation machinery reveal bacterial and eukaryotic linkages. Schumacher et al. 2015, Science
Spatial and temporal organisation of the bacterial outer membrane and its link to protein turnover. Rassam et al. 2015, Nature