Dr Colin Berry
The Insecticidal Toxins of Bacillus sphaericus and Bacillus thuringiensis
Some strains of the bacterium Bacillus sphaericus produce a variety of toxins that act specifically against mosquito larvae with few effects on non-target organisms and no harmful effects on humans. This makes it a useful agent for the biological control of mosquito populations which may constitute major pests and vectors of a range of extremely serious human diseases (including malaria, elephantiasis, yellow fever and dengue fever). Research in Dr Berry's group includes investigations of toxin mode of action, new toxin discovery, regulation of toxin gene expression and strain improvement for enhanced biological control. A recent collaboration has resulted in the complete sequencing of a Bacillus sphaericus genome and this will enhance our understanding of this biological control agent.
In order to study the genetics of the insecticidal toxins of Bacillus thuringiensis israelensis, a collaboration with the Sanger Centre was also established, which led to the elucidation of the complete sequence of the entire virulence megaplasmid (approx. 128kb) that encodes all known toxins (and helper proteins) in this bacterium. Further studies on the influence of this plasmid on its host bacterium are underway.
Parasite Aspartic Proteinases
Aspartic proteinases perform critical functions in many parasites that cause serious human or livestock diseases and are thus excellent targets for the design of novel anti-parasitic drugs. Such functions include roles in invasion of the host or as part of the parasite's digestive system. Dr Berry's group is studying these enzymes from a range of protozoan and helminthic parasites as targets for inhibitor design. The malaria parasite Plasmodium falciparum may produce up to ten aspartic proteinases (the plasmepsins). Some of these plasmepsins are involved in parasite digestion of host red cell haemoglobin and inhibition of these enzymes can lead to parasite death. Dr Berry's group has cloned and expressed plasmepsins I and II in recombinant form and has completed their full kinetic characterisation with a series of synthetic substrates and a number of inhibitors. With industrial collaborators, a compound which kills parasites in red blood cells in culture and shows selective inhibition of plasmepsin I has been identified. The results of these studies will facilitate the design of new inhibitory compounds as potential anti-malarial drugs.
Dr Berry's work has received funding from a variety of sources including The Royal Society, the UK research councils, the Welsh Development Agency, the World Health Organisation, the Leverhulme Trust, the Wellcome Trust, the British Council, the Welsh Assembly Government, the Cardiff Partnership Fund & various industrial sponsors.
- Prof Esther Alonso Becerra and Alexander Padrón, Faculty of Chemistry, University of Havana
- Dr Daniel Bur, Actelion Ltd, Switzerland
- Prof Maya Chávez, Centro de Estudio de Proteínas, University of Havana, Cuba
- Dr Ana Domingos, Instituto Nacional de Engenharia e Tecnologia Industrial, Lisbon, Portugal
- Prof Brian Federici and Dr Margaret Wirth, University of California, Riverside, USA
- Dr James McCarthy, Queensland Institute of Medical Research, Brisbane, Australia
- Dr Rose Monnerat, EMBRAPA, Brasilia, Brazil
- Dr Christina Nielsen-LeRoux, Institut Pasteur, Paris, France
- Dr David Powell, GlaxoSmithKline, Harlow, UK
- Dr Maria Helena N.L. Silva-Filha, Centro de Pesquisas Aggeu Magalhães-FIOCRUZ, Recife, Brazil
- Dr Marcelo Soares, Bthek Biotechnologia, Brasilia, Brazil
- Dr Zhiming Yuan, Wuhan Institute of Virology, Wuhan, China
- Prof Arieh Zaritsky, Ben Gurion University of the Negev, Israel