Morphologic analysis of the apicoplast formation in Plasmodium falciparum

• Grant number: 14/23330-9
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2016
• Effective date (End): December 26, 2019
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Carsten Wrenger
• Grantee: Marleen Linzke
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The malaria parasite Plasmodium falciparum possesses organelles such as mitochondrion and the chloroplast-like compartment named apicoplast which is absent in the human host. Interference with metabolic pathways present in the latter one have been proven be lethal for the parasite. During schizogony P. falciparum need to distribute this organelle to the newly generated merozites which requires the presence of specific proteins. We already identified an enzyme, MinD, belonging to the Min protein of plants. The protein is predicted to be trafficked to the apicoplast and to act as a phosphatase. The aim of the proposed application is to biochemically characterise the recombinant plasmodial enzyme and identify its role in organelle distribution by employing transgenic parasites over-expressing Strep-tagged MinD enzymes. Further mutagenic modifications of PfMinD over-expressing cells will be used to visualise morphological changes of the apicoplast of GFP expressing parasites. The discovery of proteins involved in organelle distribution is very likely to identify novel drug targets, which will be restricted to the parasite.

Scientific publications

(4)

(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)

BATISTA, FERNANDO A.; BOSCH, SORAYA S.; BUTZLOFF, SABINE; LUNEV, SERGEY; MEISSNER, KAMILA A.; LINZKE, MARLEEN; ROMERO, ATILIO R.; WANG, CHAO; MUELLER, INGRID B.; DOMLING, ALEXANDER S. S.; GROVES, MATTHEW R.; WRENGER, CARSTEN. Oligomeric protein interference validates druggability of aspartate interconversion in Plasmodium falciparum. MICROBIOLOGYOPEN, v. 8, n. 7 JUL 2019. Web of Science Citations: 0.

LUNEV, SERGEY; BUTZLOFF, SABINE; ROMERO, ATILIO R.; LINZKE, MARLEEN; BATISTA, FERNANDO A.; MEISSNER, KAMILA A.; MUELLER, INGRID B.; ADAWY, ALAA; WRENGER, CARSTEN; GROVES, MATTHEW R. Oligomeric interfaces as a tool in drug discovery: Specific interference with activity of malate dehydrogenase of Plasmodium falciparum in vitro. PLoS One, v. 13, n. 4 APR 25 2018. Web of Science Citations: 2.

LUNEV, SERGEY; BOSCH, SORAYA S.; BATISTA, FERNANDO A.; WANG, CHAO; LI, JINGYAO; LINZKE, MARLEEN; KRUITHOF, PAUL; CHAMOUN, GEORGE; DOMLING, ALEXANDER S. S.; WRENGER, CARSTEN; GROVES, MATTHEW R. Identification of a non-competitive inhibitor of Plasmodium falciparum aspartate transcarbamoylase. Biochemical and Biophysical Research Communications, v. 497, n. 3, p. 835-842, MAR 11 2018. Web of Science Citations: 0.

MEISSNER, KAMILA A.; LUNEV, SERGEY; WANG, YUAN-ZE; LINZKE, MARLEEN; BATISTA, FERNANDO DE ASSIS; WRENGER, CARSTEN; GROVES, MATTHEW R. Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation. CURRENT DRUG TARGETS, v. 18, n. 9, p. 1069-1085, 2017. Web of Science Citations: 4.