서브메뉴
검색
Accessing the Viral Cargo: Capsid Dynamics and Disassembly
Accessing the Viral Cargo: Capsid Dynamics and Disassembly
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211151454
- ISBN
- 9798382777740
- DDC
- 574.191
- 서명/저자
- Accessing the Viral Cargo: Capsid Dynamics and Disassembly
- 발행사항
- [Sl] : Harvard University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 138 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Manoharan, Vinothan N.
- 학위논문주기
- Thesis (Ph.D.)--Harvard University, 2024.
- 초록/해제
- 요약Many viruses consist of a genome encapsulated in a protective, self-assembled protein capsid. Infection requires exposure of the genomic cargo to the host cellular machinery. Because the self-assembled capsid is thought to be in a free-energy minimum in the cellular environment, this exposure requires an external energy input or a chemical change in the environment. This thesis focuses on understanding how the cargo of a viral capsid can become exposed. In the first part, I study the uncoating of bacteriophage MS2 bound to its receptor in vivo using fluorescence imaging, and I find evidence of a new extracellular uncoating pathway, suggesting that the virus could have more than one uncoating pathway to balance different risks during the early stages of infection. In the second part, I use coarse-grained molecular dynamics simulations to understand the disassembly kinetics and intermediates of a generic virus-like particle. I find that disassembly is nucleated and investigate the factors that affect the nucleation barrier. In the third part, I develop a high-throughput measurement of capsid permeability and use it to investigate how MS2 and its virus-like particles respond to different environments, showing that increased capsid dynamics can help to expose the cargo even when the particle cannot disassemble completely. I also find that the size and structure of the cargo affects the permeability. The work presented here provides new insights into the viral disassembly process and the factors that contribute to the accessibility of a viral cargo.
- 일반주제명
- Biophysics
- 일반주제명
- Virology
- 일반주제명
- Applied physics
- 일반주제명
- Microbiology
- 키워드
- Uncoating
- 기타저자
- Harvard University Engineering and Applied Sciences - Applied Physics
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
008250123s2024 us c eng d■001000017161855
■00520250211151454
■006m o d
■007cr#unu||||||||
■020 ▼a9798382777740
■035 ▼a(MiAaPQ)AAI31296972
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574.191
■1001 ▼aPaine, Amelia Wang.▼0(orcid)0000-0002-8037-6459
■24510▼aAccessing the Viral Cargo: Capsid Dynamics and Disassembly
■260 ▼a[Sl]▼bHarvard University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a138 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Manoharan, Vinothan N.
■5021 ▼aThesis (Ph.D.)--Harvard University, 2024.
■520 ▼aMany viruses consist of a genome encapsulated in a protective, self-assembled protein capsid. Infection requires exposure of the genomic cargo to the host cellular machinery. Because the self-assembled capsid is thought to be in a free-energy minimum in the cellular environment, this exposure requires an external energy input or a chemical change in the environment. This thesis focuses on understanding how the cargo of a viral capsid can become exposed. In the first part, I study the uncoating of bacteriophage MS2 bound to its receptor in vivo using fluorescence imaging, and I find evidence of a new extracellular uncoating pathway, suggesting that the virus could have more than one uncoating pathway to balance different risks during the early stages of infection. In the second part, I use coarse-grained molecular dynamics simulations to understand the disassembly kinetics and intermediates of a generic virus-like particle. I find that disassembly is nucleated and investigate the factors that affect the nucleation barrier. In the third part, I develop a high-throughput measurement of capsid permeability and use it to investigate how MS2 and its virus-like particles respond to different environments, showing that increased capsid dynamics can help to expose the cargo even when the particle cannot disassemble completely. I also find that the size and structure of the cargo affects the permeability. The work presented here provides new insights into the viral disassembly process and the factors that contribute to the accessibility of a viral cargo.
■590 ▼aSchool code: 0084.
■650 4▼aBiophysics
■650 4▼aVirology
■650 4▼aApplied physics
■650 4▼aMicrobiology
■653 ▼aBacteriophage MS2
■653 ▼aCapsid permeability
■653 ▼aFluorescence microscopy
■653 ▼aUncoating
■653 ▼aViral disassembly
■653 ▼aVirus-like particles
■690 ▼a0786
■690 ▼a0720
■690 ▼a0215
■690 ▼a0410
■71020▼aHarvard University▼bEngineering and Applied Sciences - Applied Physics.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0084
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17161855▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
