Investigation of HINT-1 involvement in calcium cellular signaling in Plasmodium falciparum

• Grant number: 15/07182-2
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2015
• End date: April 30, 2017
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Marcos Leoni Gazarini Dutra
• Grantee: Mayrim Machado Gomes Smaul
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil

Abstract

Malaria is a major public health problem, responsible for many deaths annually worldwide. The parasite responsible for this disease belongs to the genus Plasmodium. It is well known that Plasmodium proteolytic enzymes are crucial in the development and survival of the parasite within a host. Many Plasmodium cell events are regulated by calcium and the redox system. Both cell signaling mechanisms are important modulators of proteolytic activity , which subsequently control important functions of the parasite cycle . For a better understanding of the biochemical and cellular mechanisms it is necessary the study of different proteins which regulate a parasite`s intracellular signaling. The protein Hint1 is of a unknown function in the parasite , but described as a tumor suppressor and apoptosis-inducing factor in other organisms . This protein also has similar properties to calmodulin and other proteins that bind calcium, but the possible role of this protein in the calcium signaling regulation is not yet fully understood. Hint 1 has been identified for our group as a candidate of calmodulin binding in affinity column in P. falciparum . The goal of the project is to characterize the function of Hint1 in cell signaling events, proteolysis , redox system and calcium homeostasis in Plasmodium and their relationship , during the development of the intraerythrocytic cycle.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GOMES SMAUL, MAYRIM MACHADO; BUDU, ALEXANDRE; MONTAGNA, GEORGINA NURI; DA SILVA FERRARA, TAISE FERNANDA; MALUF, SARAH EL CHAMY; BAGNARESI, PIERO; FERREIRA MACHADO, MARCELO MARCONDES; DOS SANTOS, FELLIPE BRONZE; DE AZEVEDO, MAURO FERREIRA; CARMONA, ADRIANA KARAOGLANOVIC; et al. Plasmodium falciparum histidine triad protein and calmodulin modulates calcium homeostasis and intracellular proteolysis. Biochemical and Biophysical Research Communications, v. 503, n. 2, p. 722-728, SEP 5 2018. (12/24278-5, 16/15298-3, 14/07138-0, 16/02412-2, 15/19316-3, 13/12913-0, 15/00689-4, 15/11861-2, 15/07182-2, 11/20941-9)

BUDU, ALEXANDRE; GOMES, MAYRIM M.; MELO, POLLYANA M.; MALUF, SARAH EL CHAMY; BAGNARESI, PIERO; AZEVEDO, MAURO F.; CARMONA, ADRIANA K.; GAZARINI, MARCOS L.. Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum. CELLULAR SIGNALLING, v. 28, n. 3, p. 125-135, MAR 2016. (11/14403-4, 13/12913-0, 15/07182-2)