Gruppe Hemphill

THE PATHOGEN(S):

We are dealing with cyst-forming apicomplexan parasites. These include:

• Neospora caninum, which causes abortion and stillbirth in a variety of animals, and is economically most important in cattle.
• Toxoplasma gondii, which is closely related to N. caninum, and besides its outstanding importance as a veterinary pathogen, causes toxoplasmosis in humans, such as in immune-compromised individuals and upon primary infection during pregnancy affecting the fetus and the newborn.
• Besnoitia besnoiti, closely related to Neospora and Toxoplasma, and causing besnoitiosis in cattle, an emerging disease in the Mediterranean region, which is spreading into Central and Eastern Europe.

MAIN PROJECTS:

SNF project 310030_184662:

Effects of a double-edged sword: exploiting the interaction between immunity and chemotherapy in murine and ovine models of congenital neosporosis and toxoplasmosis (01.05.2019-30.04.2023)

We are interested in the development of novel therapies (drugs) and prevention strategies (vaccines) against diseases caused by apicomplexan parasites. We have identified a number of compounds that are highly effective in mouse and sheep models of Neospora and Toxoplasma infection, but do not act parasiticidal when applied at high concentrations in vitro. As these pathogens exhibit an extraordinary capacity to adapt to high drug concentrations in vitro within a relatively short time frame, we are studying the underlying mechanisms leading to the development of drug tolerance, and we are also interested in the cross-talk between chemotherapy and immune response and the impact on infection. We apply comparative proteomics with the aim to identify proteins that are upregulated in drug-adapted strains, to apply these potential vaccine candidates using suitable mouse models.

Sinergia project CRSII5_173718:

Ruthenium complexes for the treatment of protozoan diseases of medical and veterinary importance (01.09.2017-31.08.2021)

This is a collaborative project with PD Dr. Julien Furrer (Dept. of Chemistry, Bern), and Prof. Gilles Gasser (Paris-Chimietech). The chemists design and synthesize novel ruthenium-based organometallic complexes that are then first investigated for in vitro activity against T. gondii, and those exhibiting interesting properties (high anti-parasitic efficacy and low host cell toxicity), are then further studied in terms of embryotoxicity in a zebrafish embryo development model, and for in vivo activity in the Toxoplasma mouse model. In collaboration with other groups, promising compounds are also assessed in additional protozoan parasites including Trypanosoma, Theileria, Eimeria, Giardia and others.

SNF project IZSTZ_191762:

The molecular basis of adaptation of Aedes mosquitoes, vectors of viral diseases, to saltwater environments.

This project is a collaborative undertaking with Prof. Noble Surendran, University of Jaffna, Sri Lanka, and Prof. Isabel Roditi and Dr. Arunasalam Naguleswaran from the Institute of Cell Biology, Bern. The project studies Aedes mosquitoes, which transmit many viral diseases including Yellow Fever, Dengue, Zika, and Chikungunya. Aedes usually undergoes development in sweet water. However, our Sri Lankan partners have found that these insects can also develop in brackish water with higher salt content. We investigate the molecular mechanisms that enable Aedes to adapt to salt water, and study the corresponding changes by transcriptomics, immunohistochemistry and TEM. The project finances two PhD positions in Sri Lanka, and will also enable these students to spend time in Swiss laboratories to perform recombinant protein expression and TEM. In addition, a bioinformatics workshop for PhD students will be held in Sri Lanka.