Project 1: Signal transduction in the gonads
Signal transduction in the gonads of S. mansoni
A vaccine against schistosomes is not available yet. Furthermore, there is a pressing need to develop new antihelmintics due to the possibility of emerging resistance against the commonly used drug Praziquantel. Against this background understanding of essential physiological and developmental processes of schistosome biology will uncover new strategies for intervening in such processes and may reveal new ways to control the parasite1.
Towards this end, one possibility is to study the unusual reproduction biology of schistosomes. They are the only trematodes (blood flukes) which have evolved separate sexes. Beyond that, a nearly unique phenomenon in nature is the continuous pairing-contact which is essential for the development of the reproductive organs of the female.
Studies, among others from our lab, have shown that so-called signal transduction processes play important roles in this context. Molecules such as protein kinases, which can occur as cytoplasmic or transmembrane molecules, are involved in controlling important differentiation processes in the ovaries or the vitellaria of females or in the testes of males of S. mansoni 2-4. We have demonstrated that inhibiting such molecules has negative and in part fatal impact on physiological processes in adult schistosomes, including egg production5-8 (see also project 6A).
1Cioli D, Pica-Mattoccia L, Basso A, Guidi A. (2014) Schistosomiasis control: praziquantel forever? Mol Biochem Parasitol. 195(1):23-9.
2Knobloch, J., Beckmann, S., Burmeister, C., Quack, T., and Grevelding C.G. (2007) Tyrosine kinase and cooperative TGFbeta signaling in the reproductive organs of Schistosoma mansoni. Exp Parasitolo. 117:318-336.
3Beckmann, S., Quack, T., Burmeister, C., Buro, C., Long, T., Dissous, C., Grevelding C.G. (2010) Schistosoma mansoni: Signal transduction processes during the development of the reproductive organs. Parasitology 137, 497-520.
4Vanderstraete, M., Gouignard, N., Cailliau, K., Morel, M., Hahnel, S., Leutner, S., Beckmann, S., Grevelding, C.G., Dissous, C. (2014) Venus kinase receptors control reproduction in the platyhelminth parasite Schistosoma mansoni. PLoS Pathog. 10(5): e1004138.
5Gelmedin, V., Dissous, C., Grevelding, C.G. (2015) Re-positioning protein kinase inhibitors against schistosomiasis. Fut Med Chem. 7(6):737-752.
6Doerig, C. and Grevelding, C.G. (2015) Importance of kinases in Plasmodium and Schistosoma. Biochem Biophysical Acta 1854:1637–1643.
7Morel, M., Vanderstraete, M., Hahnel, S., Grevelding, C.G., Dissous, C. (2014) Receptor tyrosine kinases and schistosome reproduction: new targets for chemotherapy. Front Genet.5: 238.
8Gelmedin, V., Morel, M., Hahnel, S., Cailliau, K., Dissous, C., Grevelding, CG. (2017) Evidence for Integrin - Venus Kinase Receptor 1 Alliance in the Ovary of Schistosoma mansoni Females Controlling Cell Survival. PLoS Pathog. 13(1):e1006147.