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Genetic Studies of Malaria Parasite Invasion into Red Blood Cells
Genetic Studies of Malaria Parasite Invasion into Red Blood Cells
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152822
- ISBN
- 9798346532361
- DDC
- 575
- 서명/저자
- Genetic Studies of Malaria Parasite Invasion into Red Blood Cells
- 발행사항
- [Sl] : Harvard University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 147 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-05, Section: B.
- 주기사항
- Advisor: Duraisingh, Manoj.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2024.
- 초록/해제
- 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.
- 일반주제명
- Genetics
- 일반주제명
- Molecular biology
- 일반주제명
- Public health
- 키워드
- Erythroid cells
- 키워드
- Invasion
- 키워드
- Tropism
- 기타저자
- Harvard University Biological Sciences in Public Health
- 기본자료저록
- Dissertations Abstracts International. 86-05B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211152822
■006m o d
■007cr#unu||||||||
■020 ▼a9798346532361
■035 ▼a(MiAaPQ)AAI31559469
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a575
■1001 ▼aKeutcha, Cyrianne Sonia.▼0(orcid)0009-0009-6496-6094
■24510▼aGenetic Studies of Malaria Parasite Invasion into Red Blood Cells
■260 ▼a[Sl]▼bHarvard University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a147 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-05, Section: B.
■500 ▼aAdvisor: Duraisingh, Manoj.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2024.
■520 ▼aMalaria 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.
■590 ▼aSchool code: 0084.
■650 4▼aGenetics
■650 4▼aMolecular biology
■650 4▼aPublic health
■653 ▼aBulk segregant analysis
■653 ▼aErythroid cells
■653 ▼aHost determinants
■653 ▼aInvasion
■653 ▼aPlasmodium falciparum
■653 ▼aTropism
■690 ▼a0369
■690 ▼a0307
■690 ▼a0573
■71020▼aHarvard University▼bBiological Sciences in Public Health.
■7730 ▼tDissertations Abstracts International▼g86-05B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164020▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
