Macdonald Campus, McGill University
21,111 Lakeshore Road
Ste. Anne de Bellevue, QC, H9X 3V9
With advances in genome sequence databases, a major issue in biology today is to bridge the gap between information on the genetics of an organism and its biological characteristics, or phenotype. My research focuses on the use of a model host-parasite system to address how the genes an organism possesses influence its biological properties and the interaction between host and parasite.
Ivermectin is a member of the latest class in a series of anti-parasite drugs. Haemonchus contortus is a nematode that parasitizes the stomach of sheep throughout the world. Ivermectin resistance in H. contortus has developed in the field and we have shown that at least 4 genes appear to be involved in producing this resistance phenotype. There are several important aspects of this research.
- A biochemical and functional analysis of two of these genes, which play a fundamental role in the neurobiology of nematodes, allows a dissection of the function of the nematode nervous system.
- Genetic screens for mutations associated with drug resistance are a practical method for early detection and investigation of the evolutionary process that leads to drug resistance.
- P-glycoprotein is a generalized drug pump that seems to be involved in IVM resistance. We have found that mutations in this gene may be a general mechanism by which nematodes achieve resistance to a wide range of different anti-parasite drugs.
- We have now been able to correlate the genotype of individual parasites for these genes with their behaviour in the presence of IVM. In doing so we have demonstrated the effec of individual genetic changes on the biological phenotype of the organism.
The results we have obtained are being applied to filarial parasites that infect humans. In the future we will use this model system to dissect in detail the interaction between genes and phenotype in the nematode nervous system.
Laing R, Hunt M, Protasio AV, Saunders G, Mungall K, Laing S, Jackson F, Quail M, Beech R, Berriman M, Gilleard JS
Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans. PLoS One. 2011;6(8):e23216. Epub 2011 Aug 15.
Neveu C, Charvet CL, Fauvin A, Cortet J, Beech RN, Cabaret J
Genetic diversity of levamisole receptor subunits in parasitic nematode species and abbreviated transcripts associated with resistance. Pharmacogenet Genomics. 2010 Jul;20(7):414-25.
Beech RN, Wolstenholme AJ, Neveu C, Dent JA
Nematode parasite genes: what's in a name? Trends Parasitol. 2010 Jul;26(7):334-40. Epub 2010 May 17.
Rao VT, Accardi MV, Siddiqui SZ, Beech RN, Prichard RK, Forrester SG
Characterization of a novel tyramine-gated chloride channel from Haemonchus contortus. Mol Biochem Parasitol. 2010 Oct;173(2):64-8. Epub 2010 May 13.
Beech R, Levitt N, Cambos M, Zhou S, Forrester SG
Association of ion-channel genotype and macrocyclic lactone sensitivity traits in Haemonchus contortus. Mol Biochem Parasitol. 2010 Jun;171(2):74-80. Epub 2010 Mar 6.