Welsh School of Pharmacy

Career Profile

Current

• Professor of Microbiology, Welsh School of Pharmacy since 2007-12-06

• Honorary Professor Heriot Watt University since  2006

• Associate Professor, Director Biodefense Initiative, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland, since 2002

• Adjunct Assistant Professor, Microbiology and Immunology Department, University of Maryland at Baltimore, Medical School since 2003

 Previous

• Department Head, Biodefense Medical Countermeasures, Biological Defense Research Directorate, US Naval Medical Research Center, Washington D.C., USA. From 2003 to 2007

• Principal Scientist, Chemical and Biological Sciences, Defence Science and Technologies Laboratory,  Porton Down (MOD),  Salisbury, UK.  From 1993 to 2002

Research Interest

The principal focus of my research career has been the organism B.anthracis and its illicit use as a bio-weapon. Early work was driven by the need to develop detection assays and medical countermeasures for MOD, much of which I have been unable to publish for security reasons. In recent years, I have broadened my interests and am currently addressing the following research questions;  

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 approaches, including MLST typing and analysis of the nucleotide sequence of the B.anthracis genome, a multi-national effort that I lead, 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 and the emergence of pathogenic strains of B.cereus expressing virulence factors  thought to be unique to B. anthracis lends further support to this premise. While there is data to support the idea of horizontal gene transfer the precise mechanisms and conditions under which it occurs have yet to be defined. Outside of an infected host, B.anthracis persists in the environment as a dormant spore and as such is unable to transfer genetic material. Little is known about the environmental signals which trigger germination and support replication, essential events if gene transfer is to occur. I am using soil microcosms to determine the factors which trigger germination and to demonstrate the feasibility of environmental phage mediated gene transfer.  

Spore Structure: I was one of the first researchers to investigate the fine structure of the exosporium which comprises the outer surface of the B.anthracis spore. Rather than being inert, I have shown, with colleagues at the University Maryland Medical School, that the exosporium is decorated with enzymes which play a role in the early stages of germination and infection.

Pathogenicity: 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.

Host immune response: 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: 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.