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  

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Control Number  

joongbu:656487