자료유형  

 학위논문

Control Number  

0017164888

International Standard Book Number  

9798346390268

Dewey Decimal Classification Number  

610

Main Entry-Personal Name  

Tse, Ariana Y.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

152 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-05, Section: B.

General Note  

Advisor: Spakowitz, Andrew J.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2024.

Summary, Etc.  

요약Understanding the mechanisms for different cellular behaviors has been a goal for countless biologists and biophysicist throughout history. Cellular behavior is reliant on the coordination of a multitude of intracellular processes. Cellular behavior is incredibly complex, encompassing everything from the precise regulation of epigenetic marks for proper gene expression to the dynamic orchestrated motion of chromosomes during cell division. DNA methylation, mediated by DNA methyltransferases, plays a pivotal role in maintaining cellular identity and function. Similarly, the accurate pairing and segregation of homologous chromosomes during Prophase I of meiosis are essential for genetic diversity and stability. Each of these processes relies on interactions of various proteins and enzymes with DNA, making the study of these mechanisms an incredibly multifaceted challenge that relies on the use of complex biological models.The work presented here focuses on the development of these models and the findings that can be made from biological modeling. We utilize polymer physics models to describe the DNA environment and build upon them to include multiple levels of biological complexity. Specifically, we developed a model that predicts methylation patterns by describing the exploration of DNA methyltransferase throughout a multiscale DNA environment which exhibits the patterns of cytosine-phosphate-guanine sequences in DNA. Using this model, we recapitulated the methylation state correlation distributions of cancerous and healthy cells measured experimentally through DNA sequencing, and in doing so, predicted the aberrant DNA methyltransferase behaviors that can lead to cancerous cells.Additionally, we modeled the pairing process of homologous chromosomes, capturing influences from the nuclear confinement, the Spo11 enzyme that create double strand breaks, cohesins that structurally form chromosomal loops, and the Srs2 enzyme that disturbs the formation of crossover intermediates. From this model, we simulated the formation of crossovers, exchanges of genetic information between homologous chromosomes necessary for creating genetically diverse sperm and egg cells. Our predictions recapitulated the experimentally measured distribution of distances between crossovers, leading us to outline possible mechanisms for the biological phenomenon of crossover interference. Both of these models advanced our understanding of these complex processes and the mechanisms which govern their success. These findings offer valuable insights that could guide future research into potential therapies for cancer and various genetic disorders.

Subject Added Entry-Topical Term  

DNA methylation.

Subject Added Entry-Topical Term  

Polymers.

Subject Added Entry-Topical Term  

Monte Carlo simulation.

Subject Added Entry-Topical Term  

Physics.

Subject Added Entry-Topical Term  

Colon.

Subject Added Entry-Topical Term  

Chromosomes.

Subject Added Entry-Topical Term  

Physicists.

Subject Added Entry-Topical Term  

Epigenetics.

Subject Added Entry-Topical Term  

Yeast.

Subject Added Entry-Topical Term  

Probability distribution.

Subject Added Entry-Topical Term  

Cell division.

Subject Added Entry-Topical Term  

Biochemistry.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Developmental biology.

Subject Added Entry-Topical Term  

Genetics.

Subject Added Entry-Topical Term  

Polymer chemistry.

Subject Added Entry-Topical Term  

Statistics.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 86-05B.

Electronic Location and Access  

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Control Number  

joongbu:656186