Hoffmann Research Laboratory
Schistosome parasites locate a definitive mammalian host, penetrate the skin barrier, enter a blood or lymphatic vessel, pass through the lungs and eventually establish residency in the vasculature surrounding the liver, intestines or bladder. During this time, schistosomes evade damaging immune responses, feed on host blood, absorb biomolecules across their protective tegument and interact with diverse tissues and cells as they undergo complex developmental processes. This programme of evolutionary fine-tuned events leads to sexual maturation of the dimorphic adults culminating in the cross-tissue transmission of the pathogenic egg.
We are interested in identifying parasite gene products that are associated with these processes and have focused our studies on molecules that may have a role in invasion, migration, intravascular survival and egg transmission. Parallel to this interest, we are also fascinated by the underlying molecular, genetic and epigenetic mechanisms utilised by schistosome parasites that enable long-term survival in the bloodstream of immuno-competent hosts.
The following research areas are being investigated in our laboratory:
- The role of SmVALs (Schistosoma mansoni venom allergen like molecules) and other developmentally-regulated parasite gene products in host/schistosome interactions.
- The function of epigenetic regulators during schistosome lifecycle progression.
- Host immunomodulation by schistosome biomolecules.
- Schistosome sexual maturation.
It is the ultimate goal of these investigations to identify novel anti-schistosomal targets for combating schistosomiasis. More fundamentally however, we anticipate these studies to provide new insights into the development of parasitism, bilateral symmetry, immune-evasion strategies, sexual reproduction and organogenesis.
- Hoffmann/Chalmers/Swain labs visit the Wellcome Trust Sanger Institute (September 17-18, 2013).
- Hoffmann/Chalmers labs host the 1st England/Wales schistosomiasis conference in Gregynog (October 25-27, 2013).
Geyer, K. K., Chalmers, I. W., MacKintosh, N. D., Hirst, J. E., Geoghegan, R., Badets, M., Brophy, P. M., Brehm, K. & Hoffmann, K. F. Cytosine methylation is a conserved epigenetic feature found throughout the phylum Platyhelminthes. 9 Jul 2013. BMC Genomics. 14, 462.
Chalmers, I.W. and Hoffmann, K.F. Platyhelminth venom allergen-like (VAL) proteins: revealing structural diversity, class-specific features and biological associations across the phylum. Parasitology. 2012 139(10): 1231-1245.
Martin T. Swain, Denis M. Larkin, Conor R. Caffrey, Stephen J. Davies, Alex Loukas, Patrick J. Skelly, and Karl F. Hoffmann.Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery. Trends in Parasitol. 2011 27(12): 555-564.