A large portion of the Molecular Helminthology Laboratory is currently engaged in research projects on schistosomes. The schistosome surface is the site of intimate host-parasite interaction; nutrients are taken up across the body surface of parasites in the bloodstream and environmental sensing occurs at the surface. There is great interest in identifying and characterizing molecules at the host-exposed parasite surface for two main reasons:
- To gain a better understanding of surface biochemistry and cell biology.
- To identify molecules accessible to host immune effectors at the parasite surface. These molecules are important vaccine candidates as well as novel drug targets.
The laboratory has long history of research work characterizing the schistosome host-interactive surface and this work continues with a focus in two areas:
Characterization of Host-interactive Schistosome Surface Proteins
Published proteomic data together with bioinformatic analysis and the characterization of our recombinant anti-tegumental antibodies from schistosome infected rats have identified host-interactive membrane proteins that we hypothesize are essential for schistosome survival in the mammalian host. Currently, the Molecular Helminthology Laboratory is investing much of its effort to study schistosome membrane proteins that we predict are necessary to protect the parasites from host immune and hemostatic responses. We are also seeking to identify the most abundant schistosome tegumental proteins that are exposed to the host on the surface of schistosomula and adult worms. Recombinant antibody reagents are being developed and recombinant eukaryotic host expression systems employed for the functional characterization of these putative schistosome immune and hemostatic modulators. Hypotheses that result from these studies are subsequently tested in schistosomes using RNAi.
The Molecular Helminthology Laboratory first described RNA interference (RNAi, gene silencing) in schistosomes in 2003. The lab is currently optimizing RNAi protocols for use with different schistosome life cycle stages and using the methodology for functional genomics with particular emphasis on the host-interactive parasite surface. In addition, we are using bioinformatic analysis to guide studies seeking to characterize the molecular machinery that enables RNAi in schistosomes.
For more information about the Molecular Helminthology Laboratory's research with this model species please see the Schistosome Publications below.
A large portion of the Molecular Helminthology Laboratory is currently engaged in research projects on schistosomes.
- Angeli, A., Pinteala, M., Maier, S.S., Simionescu, B.C., Da’dara, A.A., Skelly, P.J., Supuran, C.T. 2020. Sulfonamide inhibition studies of an Î±-carbonic anhydrase from Schistosoma mansoni, a platyhelminth parasite responsible for schistosomiasis. International Journal of Molecular Sciences.
- Pirovich, D., Da'dara, A.A., Skelly, P.J. 2019. Why Do Intravascular Schistosomes Coat Themselves in Glycolytic Enzymes?. BioEssays.
- Da’dara, A.A., Angeli, A., Ferraroni, M., Supuran, C.T., Skelly, P.J. 2019. Crystal structure and chemical inhibition of essential schistosome host-interactive virulence factor carbonic anhydrase SmCA. Communications Biology.
- Elzoheiry, M., Da'dara, A.A., Nation, C.S., El-Beshbishi, S.N., Skelly, P.J. 2019. Schistosomes can hydrolyze proinflammatory and prothrombotic polyphosphate (polyP) via tegumental alkaline phosphatase, SmAP. Molecular and Biochemical Parasitology.
- Elzoheiry, M., Da'Dara, A.A., Delaforcade, A.M., El-Beshbishi, S.N., Skelly, P.J. 2018. The Essential Ectoenzyme SmNPP5 from the Human Intravascular Parasite Schistosoma mansoni is an ADPase and a Potent Inhibitor of Platelet Aggregation. Thrombosis and Haemostasis.
- Wang, Q., Da'Dara, A.A., Skelly, P.J. 2018. The blood fluke Schistosoma mansoni cleaves the coagulation protein high molecular weight kininogen (HK) but does not generate the vasodilator bradykinin. Parasites and Vectors.
- Elzoheiry, M., Da'dara, A.A., Bhardwaj, R., Wang, Q., Azab, M.S., El-Kholy, E.-S.I., El-Beshbishi, S.N., Skelly, P.J. 2018. Intravascular Schistosoma mansoni Cleave the Host Immune and Hemostatic Signaling Molecule Sphingosine-1-Phosphate via Tegumental Alkaline Phosphatase. Frontiers in immunology.
- Wang, Q., Da'dara, A.A., Skelly, P.J. 2017. The human blood parasite Schistosoma mansoni expresses extracellular tegumental calpains that cleave the blood clotting protein fibronectin. Scientific Reports.
- Skelly, P., LoVerde, P.T. 2017. Editorial. Molecular and Biochemical Parasitology.
- Da'dara, A.A., Siddons, G., Icaza, M., Wang, Q., Skelly, P.J. 2017. How schistosomes alter the human serum proteome. Molecular and Biochemical Parasitology.
- Krautz-Peterson, G., Debatis, M., Tremblay, J.M., Oliveira, S.C., Da’dara, A.A., Skelly, P.J., Shoemaker, C.B. 2017. Schistosoma mansoni Infection of Mice, Rats and Humans Elicits a Strong Antibody Response to a Limited Number of Reduction-Sensitive Epitopes on Five Major Tegumental Membrane Proteins. PLoS Neglected Tropical Diseases.
- Da’dara, A.A., de Laforcade, A.M., Skelly, P.J. 2016. The impact of schistosomes and schistosomiasis on murine blood coagulation and fibrinolysis as determined by thromboelastography (TEG). Journal of Thrombosis and Thrombolysis.
- Da’dara, A.A., Skelly, P.J. 2015. Gene suppression in schistosomes using RNAi. Methods in Molecular Biology.
- Figueiredo, B.C., Da'dara, A.A., Oliveira, S.C., Skelly, P.J. 2015. Schistosomes Enhance Plasminogen Activation: The Role of Tegumental Enolase. PLoS Pathogens.
- Da'Dara, A.A., Skelly, P.J. 2014. Schistosomes versus platelets. Thrombosis Research.
- Figueiredo, B.C., Assis, N.R.G., Morais, S.B., Ricci, N.D., Pinheiro, C.S., Martins, V.P., Bicalho, R.M., Da'dara, A.A., Skelly, P.J., Oliveira, S.C. 2014. Schistosome Syntenin Partially Protects Vaccinated Mice against Schistosoma mansoni Infection. PLoS Neglected Tropical Diseases.
- Skelly, P.J., Da'dara, A.A., Li, X.-H., Castro-Borges, W., Wilson, R.A. 2014. Schistosome Feeding and Regurgitation. PLoS Pathogens.
- Da’dara, A.A., Bhardwaj, R., Skelly, P.J. 2014. Schistosome apyrase SmATPDase1, but not SmATPDase2, hydrolyses exogenous ATP and ADP. Purinergic Signalling.
- Da'dara, A.A., Bhardwaj, R., Ali, Y.B.M., Skelly, P.J. 2014. Schistosome tegumental ecto-apyrase (SmATPDase1) degrades exogenous pro-inflammatory and pro-thrombotic nucleotides. PeerJ.
- Skelly, P.J. 2013. The use of imaging to detect schistosomes and diagnose schistosomiasis. Parasite Immunology.