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Decoding Plasmodium signaling at molecular level as a new tool to the development of new antimalarials

Grant number: 17/08684-7
Support type:Research Projects - Thematic Grants
Duration: February 01, 2019 - January 31, 2024
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Célia Regina da Silva Garcia
Grantee:Célia Regina da Silva Garcia
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Fabio Trindade Maranhão Costa ; Maria Regina D'Império Lima
Associated scholarship(s):19/08974-0 - Maintenance of Cell Biology Laboratory and culture of HEK293T cells, BP.TT
19/09490-7 - Screening of novel ligands for PfSR1, a putative GPCR-like receptor and identification of potential IP3 receptor in calcium signaling in the Plasmodium falciparum, BP.PD


Malaria stands as the third most dangerous infectious disease after HIV/AIDS and tuberculosis that afflict mankind. The last decade studies pointed that pathogens have developed sophisticated cell signaling networks that allow for both cell-cell communication as well as sensing the external environment. In this direction, single cell protozoan parasites have to develop systems to withstand relatively large alterations in their external environments, including existing in the mammalian host with complex defense systems. In addition to depicting a complex biology, with a sexual and asexual developmental stages, malaria parasite, is exposed to distinct microenvironments within the vector cycle as well as during its development inside a vertebrate. The overall objective of this project is to understand how the parasite detects signaling from its milieu, what are the molecular components involved in transducing this signaling. We recently reported that purinergic signaling could be involved in TNF perception by P. falciparum. We plan to dissect the involvement of purinergic receptor signaling in P. falciparum cell cycle thus unraveling what is the participation of a P2X7 receptor in TNF signaling. We will use the PfGCaMP3 parasites as well as other molecular and cellular tools to understand signaling pathways in malaria parasite aiming to disrupt this signaling. (AU)