13 jul 2022 - 14:40 CET
Our collague David Arranz-Solís has been awarded with a UNA4CAREER postdoctoral Fellowship for the next three years.
UNA4CAREER is a programme funded by the Marie Skłodowska-Curie COFUND Programme at the Complutense University that aims to recruit excellent and experienced researchers.
ABSTRACT OF THE PROPOSAL
Toxoplasma gondii is a major cause of abortion in humans and livestock, thereby producing a significant public health hazard and economic losses. Most of Toxoplasma’s virulence factors have been explored using mouse models; however, the murine immune response differs significantly from that of humans and farm animals. Thus, despite Toxoplasma’s enormous economic and health implications, little is known about the parasite factors that cause foetal mortality and vertical transmission. In an effort to dissect the pathogenic mechanisms responsible for the abortion caused by Toxoplasma, an innovative approach that extends from the molecule to the animal will be adopted in the present project. To this end, we will first explore the molecular mechanisms underlying the parasite-induced pathogenesis of early abortion by investigating the infection dynamics, clinical outcome, lesions, parasite burden and both local and peripheral immune response in a pregnant sheep model of toxoplasmosis. Since inflammation in the placenta has been associated with early abortions in humans and animals, we will subsequently investigate the role of one of the parasite effectors responsible for the induction of host inflammation in these abortions in our characterised model by using knockout parasites generated by CRISPR-Cas9 gene editing techniques. This multidisciplinary project constitutes an innovative challenge in Toxoplasma host-parasite interactions, as the in vivo effect of knockout strains for specific virulence factors has not been reported before in an animal model relevant for humans. The results derived from this proposal will significantly advance the understanding of the mechanisms of Toxoplasma early abortions and help in the design of transmission-blocking vaccines or drugs. Because Toxoplasma has been associated with women who had spontaneous abortions, these results will not only produce economic savings in the livestock industry but will also directly improve human health.