Project description
A novel target for malaria treatment
Malaria remains one of the most prevalent parasitic diseases. The emergence and spread of drug-resistant parasites threatens existing treatments and necessitates the constant development of anti-malaria drugs against new targets. The EU-funded SUBUN project will direct inhibitor development towards the Plasmodium-specific subtilisin SUB1, a protease implicated in the egress of the parasite from human infected cells. Researchers combining expertise in medicinal chemistry, biochemistry, structural biology and parasitology aim at identifying potent and selective SUB1 inhibitors, which are expected to have both prophylactic and therapeutic values. Most importantly, they will be able to target all stages of the parasite life cycle, fulfilling the WHO criteria on antimalaria agents.
Objective
The Researcher AK Puszko will be in charge of the development of peptidase inhibitors with potential interest in the treatment of Malaria.
Malaria is the most important human parasitic disease and multi-resistant parasites seriously threaten its treatment and control. The situation strengthens the constant need to fuel the antimalarials pipeline with candidates active on new targets, expressed at essential stages of Plasmodium. The egress of merozoites from infected host cells is such a pivotal step that strictly depends upon parasite proteases, including a novel highly promising target, the Plasmodium-specific subtilisin SUB1, for which no useful inhibitor has been discovered yet. SUB1 plays a key role in the egress from hepatocytes and erythrocytes, including for male gametes (involved in parasite’s transmission via the Anopheles vector), indicating that an inhibitor would have both prophylactic and therapeutic value and obey to most severe WHO’s criteria of future anti-malarials, i.e. targeting all stages of parasite life cycle. Based on Hosts’ promising results, including the resolution of crystallographic structures of SUB1-inhibitor complexes, the SUBUN project aims at identifying highly potent and selective SUB1 inhibitors, active against parasite growth in vitro and in vivo. Such innovative pre-lead candidate(s) will be patented before results dissemination within academia, industry and to wider audience.
This project will combine expertise in molecular design, medicinal chemistry, biochemistry, structural biology and parasitology. In this multidisciplinary context, the project will benefit AK Puszko who will gain extensive knowledge in new fields well established in the Host and secondment Host laboratories. This, together with scientific and transferable trainings, opportunities to develop network, communication to non-scientific audience, will strengthen her ability to become a leader in the new topic and establish her own research group in the future.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
75794 Paris
France