NotToKill-NotToDie · Unrevealing dry season Plasmodium falciparum replication biology
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-07-01 → 2021-06-30
- EU contribution
- €174,806
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
Unrevealing dry season Plasmodium falciparum replication biology
The Action with acronym “NotToKill-NotToDie” looks into how P. falciparum parasites are able to survive during the long 6 moths’ dry season in of certain malaria endemic regions without being cleared by the immune system. P. falciparum persists at very low parasitemia in close to one third of the children during the dry season without causing symptoms, and representing an essential reservoir of parasites needed to restart transmission as the rainy season ensues and mosquitos re-appear. The research questions on the mechanism/s underneath this important phenomenon, with a special emphasis on unrevealing a potential alteration in the parasite’s intrinsic capacity to replicate. Such topic is important because society needs to propose new and innovative routes to tackle malaria; and prophylactic drugs during the dry season when parasite numbers are low, and the prevalence of infected people much lower than in the transmission season, seems a good way forward for alternative treatment strategies. Not only is there widespread lack of knowledge on the parasite’s intrinsic biology leading to asymptomatic infections under this scenario, but also an uncertainty on how under similar exposure to malaria some people carry parasites triggering severe malaria outcomes during the transmission season while others just remain asymptomatic. Although working during the dry season in a malaria endemic country poses a challenge i, we have been able to address the topic of parasite replication through a variety of innovative approaches. Objectives of this MSCA have been to (1) Characterize dry-season parasites through expression kinetics of parasite replication-associated genes and their phenotype, and (2) Investigate PfCRK4 regulation of P. falciparum cell cycle progression, and its role in dry season transcription modulation. A parallel goal of the MSCA Individual Fellowship (Reintegration) is to foster the development of the individual researcher, achieve a productive international collaboration and disseminate the work in the local society.
Data: CORDIS, © European Union
Project objective
Plasmodium falciparum is responsible for over 200 million yearly malaria cases and the major burden is upon African children. Public health strategies to control and ultimately eradicate malaria are very much needed. In Africa, seasonal transmission of this mosquito-borne parasite is very common. Infections in adults are clinically silent whilst in children it generally leads to clinical disease with nearly half a million deaths each year. The dry season represents a major challenge for the parasite’s survival due to the absence of the transmission vector; yet, P. falciparum seems to be capable of maintaining low parasitemias just enough not to kill but not to die. During the dry season, an important fraction of these children remains clinically silent for months despite the decrease in P. falciparum-specific antibody levels. This low parasitemia reservoir is indispensable to spread transmission in the following rainy season. How do parasites not increase to the point of causing clinical malaria in these children during the dry season? We hypothesize that during the dry season with no mosquitoes available to transmit, continuous rounds of P. falciparum blood stage replication lead to a differential gene expression related to cell cycle progression allowing the maintenance of low levels of parasitemia. The Center for Infectious Diseases, University Hospital Heidelberg has an interdisciplinary and translational orientation and is embedded in partnerships with groups in malaria endemic countries, representing a unique environment to execute the objectives of this project. I offer translational expertise in the malaria from my previous experience in malaria endemic areas of Brazil as well as in state-of-the-art laboratories in the US. This ambitious yet feasible project also offers the opportunity for me to broaden my expertise in malaria by acquiring knowledge in new area, which will allow me to build a solid background from which to become an independent researcher.
Original text from CORDIS.
Participants
- UNIVERSITATSKLINIKUM HEIDELBERG · HeidelbergCoordinatorGermany
Links
- View on CORDIS
- DOI: 10.3030/839998
- https://ec.europa.eu/info/funding-tenders/opportunities/portal/screen/myarea/projects
Data: CORDIS, © European Union