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Accessing the Viral Cargo: Capsid Dynamics and Disassembly.
Accessing the Viral Cargo: Capsid Dynamics and Disassembly.
상세정보
- 자료유형
- 학위논문
- Control Number
- 0017161855
- International Standard Book Number
- 9798382777740
- Dewey Decimal Classification Number
- 574.191
- Main Entry-Personal Name
- Paine, Amelia Wang.
- Publication, Distribution, etc. (Imprint
- [S.l.] : Harvard University., 2024
- Publication, Distribution, etc. (Imprint
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- Physical Description
- 138 p.
- General Note
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- General Note
- Advisor: Manoharan, Vinothan N.
- Dissertation Note
- Thesis (Ph.D.)--Harvard University, 2024.
- Summary, Etc.
- 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.
- Subject Added Entry-Topical Term
- Biophysics.
- Subject Added Entry-Topical Term
- Virology.
- Subject Added Entry-Topical Term
- Applied physics.
- Subject Added Entry-Topical Term
- Microbiology.
- Index Term-Uncontrolled
- Bacteriophage MS2
- Index Term-Uncontrolled
- Capsid permeability
- Index Term-Uncontrolled
- Fluorescence microscopy
- Index Term-Uncontrolled
- Uncoating
- Index Term-Uncontrolled
- Viral disassembly
- Index Term-Uncontrolled
- Virus-like particles
- Added Entry-Corporate Name
- Harvard University Engineering and Applied Sciences - Applied Physics
- Host Item Entry
- Dissertations Abstracts International. 85-12B.
- Electronic Location and Access
- 로그인을 한후 보실 수 있는 자료입니다.
- Control Number
- joongbu:656487
MARC
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■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[S.l.]▼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.
