Abstract

Accomplishments during the year: 1. We continue the search for new receptors through genome-wide analysis of viable merozoites. 2. The red cell receptor for EBL-1, a Duffy-like ligand on P. falciparum merozoites, is glycophorin B. 3. The immune response to RH4 and EBA-175 has been studied. This work continues to expand our understanding of parasite invasion of red cells by identifying the receptors and ligands and determining the potential of these targets for vaccine development. We show that recombinant P. falciparum RH 4 can block invasion but antibodies to PfRH4 cannot block invasion. 4. Study the changes in the histone modifications of nucleosomes and the nucleosome position of RH4 and PEBL to correlate with the change of expression in Dd2 to Dd2/nm. 5. Domains structure of CIDR1 and DBL3x of var2CSA has been identified. 6. Continue to study the cytoplasmic domains of molecules in the moving junction to determine if they bind to aldolase or other molecules that bind actin. Continue to study the role of RH1 and RH2 as targets for vaccine development. Studying viable merozoites during invasion to follow the moving junction and the effect of anti-AMA1 on invasion.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI000241-28
Application #
7964209
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
28
Fiscal Year
2009
Total Cost
$466,443
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Azasi, Yvonne; Lindergard, Gabriella; Ghumra, Ashfaq et al. (2018) Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in EPCR-binding function. Proc Natl Acad Sci U S A 115:1063-1068
Bansal, Abhisheka; Molina-Cruz, Alvaro; Brzostowski, Joseph et al. (2018) PfCDPK1 is critical for malaria parasite gametogenesis and mosquito infection. Proc Natl Acad Sci U S A 115:774-779
Akkaya, Munir; Akkaya, Billur; Kim, Ann S et al. (2018) Toll-like receptor 9 antagonizes antibody affinity maturation. Nat Immunol 19:255-266
Arora, Gunjan; Hart, Geoffrey T; Manzella-Lapeira, Javier et al. (2018) NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. Elife 7:
Gunalan, Karthigayan; Niangaly, Amadou; Thera, Mahamadou A et al. (2018) Plasmodium vivax Infections of Duffy-Negative Erythrocytes: Historically Undetected or a Recent Adaptation? Trends Parasitol 34:420-429
Niangaly, Amadou; Karthigayan Gunalan; Amed Ouattara et al. (2017) Plasmodium vivax Infections over 3 Years in Duffy Blood Group Negative Malians in Bandiagara, Mali. Am J Trop Med Hyg 97:744-752
Miller, Louis H (2017) The Impact of Ken Warren's Leadership of the Rockefeller Foundation's Great Neglected Diseases Program on the Future of Malaria Research. Am J Trop Med Hyg 97:1958
Bansal, Abhisheka; Molina-Cruz, Alvaro; Brzostowski, Joseph et al. (2017) Plasmodium falciparum Calcium-Dependent Protein Kinase 2 Is Critical for Male Gametocyte Exflagellation but Not Essential for Asexual Proliferation. MBio 8:
Riggle, Brittany A; Miller, Louis H; Pierce, Susan K (2017) Do we know enough to find an adjunctive therapy for cerebral malaria in African children? F1000Res 6:2039
Sherling, Emma S; Knuepfer, Ellen; Brzostowski, Joseph A et al. (2017) The Plasmodium falciparum rhoptry protein RhopH3 plays essential roles in host cell invasion and nutrient uptake. Elife 6:

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