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Molecular Co-Evolution Between SARS-CoV-2 and Human Antibodies
Molecular Co-Evolution Between SARS-CoV-2 and Human Antibodies
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202103537
- ISBN
- 9798280717008
- DDC
- 574
- 저자명
- Moulana, Alief.
- 서명/저자
- Molecular Co-Evolution Between SARS-CoV-2 and Human Antibodies
- 발행사항
- [Sl] : Harvard University, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 123 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
- 주기사항
- Advisor: Desai, Michael.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2025.
- 초록/해제
- 요약The COVID-19 pandemic disrupted global health systems but simultaneously offered a rare opportunity to observe the rapid co-evolution of a virus, SARS-CoV-2, with the human immune system in real time. This evolutionary interplay is often thought of as a molecular arms race, in which both pathogen and host must continually adapt to changes in each other's phenotype. This dynamic is particularly pronounced at the molecular recognition level. Human antibodies evolve (via affinity maturation) to better neutralize the viral antigens (e.g., SARS-CoV-2 spike protein), while the virus, in turn, accumulates mutations that confer immune escape. In this dissertation, I present four projects that explore the co-evolutionary landscape between viral and immune proteins. Chapters 1 and 2 focus on the combinatorial mutagenesis of the SARS-CoV-2 spike receptor-binding domain (RBD) to measure the individual and combined effects of Omicron BA.1 mutations on ACE2 binding affinity (Chapter 1) and antibody evasion (Chapter 2). Chapter 3 extends this approach to later Omicron subvariants, using high-throughput genotype-to-phenotype mapping to investigate how mutational effects depend on genetic background across divergent lineages. Finally, Chapter 4 shifts focus to the host immune response, using deep sequencing of human peripheral blood B cell repertoires and yeast display of candidate antibodies to measure evolving antibody phenotypes. Together, these studies provide an integrated view of viral and immune co-evolution, inferring the molecular principles that govern host-pathogen interactions and the trajectory of viral adaptation.
- 일반주제명
- Biology
- 일반주제명
- Immunology
- 일반주제명
- Virology
- 키워드
- B cell
- 키워드
- Binding affinity
- 키워드
- Evolution
- 기타저자
- Harvard University Biology Organismic and Evolutionary
- 기본자료저록
- Dissertations Abstracts International. 86-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798280717008
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aMoulana, Alief.▼0(orcid)0000-0002-0389-7082
■24510▼aMolecular Co-Evolution Between SARS-CoV-2 and Human Antibodies
■260 ▼a[Sl]▼bHarvard University▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a123 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-12, Section: B.
■500 ▼aAdvisor: Desai, Michael.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2025.
■520 ▼aThe COVID-19 pandemic disrupted global health systems but simultaneously offered a rare opportunity to observe the rapid co-evolution of a virus, SARS-CoV-2, with the human immune system in real time. This evolutionary interplay is often thought of as a molecular arms race, in which both pathogen and host must continually adapt to changes in each other's phenotype. This dynamic is particularly pronounced at the molecular recognition level. Human antibodies evolve (via affinity maturation) to better neutralize the viral antigens (e.g., SARS-CoV-2 spike protein), while the virus, in turn, accumulates mutations that confer immune escape. In this dissertation, I present four projects that explore the co-evolutionary landscape between viral and immune proteins. Chapters 1 and 2 focus on the combinatorial mutagenesis of the SARS-CoV-2 spike receptor-binding domain (RBD) to measure the individual and combined effects of Omicron BA.1 mutations on ACE2 binding affinity (Chapter 1) and antibody evasion (Chapter 2). Chapter 3 extends this approach to later Omicron subvariants, using high-throughput genotype-to-phenotype mapping to investigate how mutational effects depend on genetic background across divergent lineages. Finally, Chapter 4 shifts focus to the host immune response, using deep sequencing of human peripheral blood B cell repertoires and yeast display of candidate antibodies to measure evolving antibody phenotypes. Together, these studies provide an integrated view of viral and immune co-evolution, inferring the molecular principles that govern host-pathogen interactions and the trajectory of viral adaptation.
■590 ▼aSchool code: 0084.
■650 4▼aBiology
■650 4▼aImmunology
■650 4▼aVirology
■653 ▼aB cell
■653 ▼aBinding affinity
■653 ▼aEvolution
■653 ▼aGenotype-to-phenotype map
■653 ▼aMolecular recognition
■690 ▼a0306
■690 ▼a0982
■690 ▼a0720
■71020▼aHarvard University▼bBiology, Organismic and Evolutionary.
■7730 ▼tDissertations Abstracts International▼g86-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17357615▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
