MALART
Financiado
Cellular basis of Artemisinin resistance in malaria parasites
Blood stages of the protozoan parasite Plasmodium falciparum are responsible for malaria, a disease that kills more than 400'000 people annually. During its development in red blood cells the parasite internalises a large part of...
Blood stages of the protozoan parasite Plasmodium falciparum are responsible for malaria, a disease that kills more than 400'000 people annually. During its development in red blood cells the parasite internalises a large part of the host cell cytosol (hemoglobin) in an endocytic process and digests it in its food vacuole. We recently identified a critical connection of this hemoglobin endocytosis with resistance of the parasite to the current frontline drug Artemisinin, revealing the mechanism of resistance. Artemisinin is activated by hemoglobin degradation products and we found that Artemisinin resistant parasite endocytose less. Using a toolbox of recently established approaches to carry out functional studies in malaria parasites, we identified an entire series of proteins involved in endocytosis that are involved in resistance to Artemisinin. This included Kelch13, the molecular marker of Artemisinin resistance in field samples. This provides us with a unique opportunity (i) to elucidate how these molecules orchestrate endocytosis, a prominent essential process in these parasites that so far is not understood on a molecular level, (ii) to specifically understand the role of Kelch13 in this process and in resistance, and (iii) to elucidate the reason for the fitness cost that is associated with Artemisinin resistance and the compensatory mechanisms the parasite uses to mitigate them. We expect this research program to not only elucidate so far elusive key aspects of the cell biology of this important parasite, but also to identify critical constraints of Artemisinin resistant parasites and possible ways to circumvent ART resistance.
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Duración del proyecto: 63 meses
Fecha Inicio: 2021-08-26
Fecha Fin: 2026-11-30
Fecha Fin: 2026-11-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-08-26
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-ADG:
ERC ADVANCED GRANT
Cerrada
hace 4 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
BERNHARDNOCHTINSTITUT FUER TROPENMEDIZIN
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
417.32K€ |
Participante