Most of our applied research has been driven by problems from the life sciences and biomedicine (DNA microarray data analysis related to cancer, genome-wide association studies; next-generation sequencing; for older papers, see here).

1. Analysis of transcriptomic changes due to vaccination against bovine tuberculosis [NEW]

This new project is a collaboration with IBERS, University of Aberystwyth, UK.

2. Protein extraction and identification in Park Grass Experiment soil

Quinn G.A., Abdelhameed A., Banat I.M., Berrar D., Doerr S., Dudley E., Francis L.W., Gazze S.A., Hallin I., Matthews P., Swain M.T., Whalley R., and van Keulen G. (2020) Parallel protein extraction methods increase the diversity of protein identification in Park Grass Experiment soil. Under review.

3. Transcriptomics and epigenetics of S.mansoni

In a collaboration with the Hoffmann Lab at IBERS, University of Aberystwyth, UK, we are investigating the molecular biology of the pathogenic parasite Schistosoma mansoni. Schistosoma is the genus of a parasitic worm that causes schistosomiasis, an acute and chronic disease that currently affects more than 234 million people [1], notably in sub-Saharan Africa but also in many tropical and subtropical regions in south-east Asia. Schistosomiasis is one of the most serious neglected tropical diseases, causing an estimated 200,000 deaths per year [1]. Schistosomiasis is caused by three major blood fluke species within the phylum Platyhelminthes, genus Schistosoma: S.japonicum, S.haematobium, and S.mansoni [3]. When these worms come in contact with humans in infested waters, they penetrate the skin and complete their life cycle in their human host. The liver is the primary site for the worm’s eggs, which can cause potentially fatal liver cirrhosis. Poor and rural communities without adequate access to sanitation are most affected by schistosomiasis, and children are particularly vulnerable. Currently, there exist no prophylactic vaccines against this chronic and debilitating disease. One of the main drugs for treating infections is currently Praziquantel. However, there is growing concern that the parasite could develop drug resistance, so research on new anthelmintic drugs and vaccines is urgently needed [2].

A particularly challenging problem is the fact that the worm's susceptibility to drugs depends on the worm's developmental stage. For example, worm larvae occupy different locations in the human host than adult worms, and the efficiency of a drug depends on this location. Gaining deeper insights into the transcriptome and epigenetics of schistosoma at different developmental stages could hold the key to the development of new drugs and vaccines, and ultimately lead to the eradication of schistosomiasis.

We have recently [4] found that:

• The ribonucleoside 5-azacytidine (5-AzaC) inhibits schistosome egg production.

• 5-AzaC modulates schistosome transcription and translation.

• Schistosome stem cell proliferation and maintenance are affected by 5-AzaC.

References

[1] Reimers N., Homann A., Höschler B., Langhans K., Wilson R.A., Pierrot C., et al. (2015) Drug-induced exposure of schistosoma mansoni antigens SmCD59a and SmKK7. PLoS Neglected Tropical Diseases 9(3):e0003593. doi:10.1371/journal.pntd.0003593.

[2] Swain M., Larkin D.M., Caffrey C.R., Davies S.J., Loukas A., Skelly P.J., Hoffmann K.F. (2011) Schistosoma comparative genomics: integrating genome structure, parasite biology and anthelmintic discovery. Trends Parasitology 27(12):555-64.

[3] Geyer K.K., Rodríguez López C.M., Chalmers I.W. et al. (2011) Cytosine methylation regulates oviposition in the pathogenic blood fluke Schistosoma mansoni. Nature Communications 2, Article: 424; doi:10.1038/ncomms1433.

[4] Geyer K.K., Munshia S.E., Vickers M., Squance M., Wilkinson T.J., Berrar D., Chaparroe C., Swain M.T., Hoffmann K.F. (2018) The anti-fecundity effect of 5-azacytidine (5-AzaC) on Schistosoma mansoni is linked to dis-regulated transcription, translation and stem cell activities. International Journal for Parasitology: Drugs and Drug Resistance. available at https://www.sciencedirect.com/science/article/pii/S2211320718300150