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Prof Les Baillie 


General

Research Interests

Evolution, ecology and the role of bacteriophages in horizontal gene transfer:

My working hypothesis is that B. anthracis evolved from a strain of B.cereus through the horizontal acquisition of virulence factors from other bacilli. Using a number of molecular approaches, we have generated considerable data in support of this hypothesis. The presence of conserved prophages in the genome of every isolate of B.anthracis examined to date (>300 isolates) points to phages, in addition to plasmids, playing a role in gene transfer and evolution. Our recent isolation of phages capable of infecting B.anthracis and other members of the B.cereus group will enable use to determine the environmental conditions under which gene transfer occurs

 

Detection of Anthrax

Given the threat posed by B. anthracis in the context of Bioterrorism there is an urgent need to develop detection assays capable of detecting spores in the environment and diagnosing infection. An ideal assay would be highly specific, could be used with minimal sample preparation and little if any support equipment, give rapid results in <60 sec, be highly stable at room temperature and could be used repeatedly. In collaboration with colleagues in the department of Microbiology and Immunology, University of Maryland in Baltimore we are working to develop thermal stable single chain antibodies from sharks for the detection of anthrax spores and toxin. Shark produced antibodies have been shown to maintain there antibody binding capacity following prolonged heat treatment thus raising the possibility of developing extremely stable assays (Stanfield et al., 2004). In collaboration with Dr Chris Geddes, a fellow faculty member at MBC we are also developing assays based on metal enhanced flourescence which can detect nanogram levels of anthrax biomarkers in human blood in as little as 30 seconds.

 

Pathogenecity of Anthrax

I have a particular interest in understanding the cellular event following the infection of macrophages by B.anthracis spores. My recent data suggests that even though the spore triggers a number of pathogen pattern recognition receptors, it is still able to ameliorate antibacterial killing mechanisms such as nitric oxide. Following successful intracellular germination the organism expresses a complex network of virulence factors which enable it to escape from the cell. I have a long term interest in understanding the mechanisms which regulate in vivo virulence factor expression and am currently investigating the role of the inducible PlcR virulence regulon with leading US and Russian researchers based at the NIH campus in Bethesda, Maryland.

 

Anthrax - Host immune responses

I have a long term interest in understanding the immune response of immunized and infected individuals as a means of identifying mechanisms of protection. In collaboration with clinicians in Turkey where anthrax is endemic, we have characterized the immune response of infected and immunized individuals, and have shown antibodies to be the key mediator of protection. I am scientific advisor to two international companies currently developing antibody based therapies. I am also investigating the role of human memory B cells with colleagues at Emory Medical School in Atlanta. In a related effort I am working on a project with the UK MOD to optimize the immunization schedule of the UK vaccine. Finally I am a collaborator in a multi-national US NIH funded project lead by Imperial College, London to develop DNA vaccines expressing B and CD4 T cell epitopes which confer protection against anthrax and plague.

 

Vaccines against Anthrax

The development of vaccines against anthrax has been a central strand of my research career. I have developed two anthrax vaccines, one based on recombinant protein (UK MOD) and the other a DNA vaccine (US Navy) both of which have progressed to clinical trials. My current effort is focused on developing needle free vaccine delivery platforms such as micro-encapsulation and attenuated strains of Salmonella capable of conferring protection following oral dosing.

 

Therapeutic antibodies

Preformed antibodies can confer instant protection against infectious agents. Working with colleagues in Holland we have successfully isolated human monoclonal antibodies from immunised humans and demonstrated their ability to confer protection in animal models. In addition we have developed plant based systems which express human antibodies as a low cost production system.

 

Collaborators

Evolution, ecology and the role of bacteriophages in horizontal gene transfer

  • Dr Tim Read, US Navy, Washington, USA
  • Professor Gus Priest, Heriot Watt, Edinburgh

Detection

  • Professor Chris Geddes, University of Maryland Biotechnology Center, Baltimore, MD, USA

Pathogenesis

  • Dr Andrei Pomerentsev National Institute of Health, Bethesda, MD, USA
  • Professor Alan Cross, University of Maryland Medical School, Baltimore, MD, USA
  • Professor Gerald Rosen, University of Maryland School of Pharmacy, Baltimore, MD,USA
  • Professor Colin Harwood, University of Newcastle, UK

 Host immune responses

  • Dr Hugh Dyson, Dstl Porton Down, UK
  • Dr Andy Simpson, Dstl Porton Down, UK
  • Dr Di Williamson, Dstl Porton Down, UK
  • Professor Danny Altmann, Imperial College, UK
  • Professor John Robinson, University of Newcastle, UK

Vaccines

  • Dr Helen Atkins, Dstl Porton Down, UK
  • Dr Marcela Parseti, University of Maryland Medical School, Baltimore, MD USA
  • Dr Vidadi Yusobov, Fraunhofer USA, Delware, USA
 Antibodies
  • Dr Vidadi Yusobov, Fraunhofer USA, Delware, USA
  • Dr Mark Albrecht, Naval Medical Research Center, Washington, US
  • Dr Herman Groen, IQ Corporation, Groeningen, The Netherlands,

 

Key Expertise

Working with Containment level 3 micro-organisms, bacterial spores, bacteriophages, molecular biology, vaccine expression and delivery systems, DNA vaccines, antibody assays, immune signalling, innate immunity

 

Current Research Funding

  • US National Institute of Health - Rational Design of an Anthrax Toxin Neutralizing Vaccine.
    The major goal is to construct an oral, single dose vaccine based on a strain of Salmonella typhimurium.
  • US National Institute of Health - Large Scale antibody and T cell epitope discovery program.
    The major goal is to identify the human CD4 T cell epitopes within the anthrax and plague lead vaccine antigen candidates
  • Marie Curie International Reintegration Grants (IRG)FP7-PEOPLE-2007-4-3-IRG. The contribution of the exosporium of Bacillus anthracis to survival