자료유형  

 학위논문

Control Number  

0017164020

International Standard Book Number  

9798346532361

Dewey Decimal Classification Number  

575

Main Entry-Personal Name  

Keutcha, Cyrianne Sonia.

Publication, Distribution, etc. (Imprint  

[S.l.] : Harvard University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

147 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-05, Section: B.

General Note  

Advisor: Duraisingh, Manoj.

Dissertation Note  

Thesis (Ph.D.)--Harvard University, 2024.

Summary, Etc.  

요약Malaria is a global health burden, particularly affecting African countries. The invasion of red blood cells (RBCs) by Plasmodium falciparum is an essential stage in the parasite's life cycle and is crucial for establishing virulence. The parasite employs various invasion ligands to interact with host surface receptors to invade RBCs through various pathways. While many of these ligand-receptor interactions are well understood, the impact of polymorphisms in parasite ligands and host receptors, resulting from selection pressures, on these interactions remains unclear. This study uses genetic methodologies to scrutinize novel host and parasite determinants involvement in P. falciparum invasion. In our investigation of the functional roles of host determinants in P. falciparum invasion, we generated and characterized a novel immortalized erythroid cell line, BF cells. We characterized the maturation profiles, morphology, and biophysical parameters, and invasion efficiency of enucleated differentiated BF-RBCs. Our findings indicated that enucleated BF-RBCs exhibit that enucleated BF-RBCs are comparable to reticulocytes generated from primary HSCs. Finally, we demonstrated the genetic adaptability of BF cells by deleting several host determinant genes and characterized the effects of ADP-Ribosyltransferase 4 (ART4) RBC gene deletion in BF-RBCs to elucidate the role of host receptor ART4 in P. falciparum invasion.On the parasite front, we identified parasite determinants mediating invasion pathway utilization through bulk segregant analysis. Our study revealed that the known invasion ligand, RH2b, and novel candidate MSP1 mediate alternative invasion pathways. The parental strains used for bulk segregant analysis inherited different alleles of MSP1 dimorphism - the MAD20-like and the K1-like MSP1. We showed that the MAD20-like and the K1-like MSP1 parasites have comparable merozoite counts per schizont and MSP1 expression level. Lastly, we pinpointed an epistatic relationship between MSP1 and Rh2b in mediating parasite utilization of the alternative invasion pathway.

Subject Added Entry-Topical Term  

Genetics.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Public health.

Index Term-Uncontrolled  

Bulk segregant analysis

Index Term-Uncontrolled  

Erythroid cells

Index Term-Uncontrolled  

Host determinants

Index Term-Uncontrolled  

Invasion

Index Term-Uncontrolled  

Plasmodium falciparum

Index Term-Uncontrolled  

Tropism

Added Entry-Corporate Name  

Harvard University Biological Sciences in Public Health

Host Item Entry  

Dissertations Abstracts International. 86-05B.

Electronic Location and Access  

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Control Number  

joongbu:656579