자료유형  

 학위논문

Control Number  

0017164287

International Standard Book Number  

9798342138642

Dewey Decimal Classification Number  

612

Main Entry-Personal Name  

Lessenger, Alexander T.

Publication, Distribution, etc. (Imprint  

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

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

76 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-04, Section: B.

General Note  

Advisor: Feldman, Jessica.

Dissertation Note  

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

Summary, Etc.  

요약Cell size and biosynthetic capacity generally increase with increased DNA content. Polyploidy, the condition of having more than two copies of the genome in a single cell, has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood in multicellular organisms, and the impacts of polyploidy in non-disease states is not well studied. Therefore, I used polyploid cells as a model to test whether and how the amount of DNA is limiting and describe the physiological impacts of limited scaling on cells and organisms. I begin by summarizing how the size of organelles and the abundance of molecules changes with DNA concentration and how these observations inform our understanding of how DNA content may mechanistically limit biosynthesis. I then explore the impacts of reduced polyploidy in two naturally polyploid tissues, the nematode intestine and skin.First, I show that polyploidy in the C. elegansintestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with more dilute mRNA. Highly-expressed transcripts were more sensitive to this mRNA dilution, whereas lowly-expressed genes were partially compensated -- in part by loading more RNA Polymerase II on the remaining genomes. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing production of translational machinery at the expense of specialized, cell-type specific proteins.Second, I explore how polyploidy in the skin relates to body size and the major body size-signaling pathway. Polyploidy can increase body and organ size, and it has been proposed that the TGF-beta signaling pathway controls C. elegans body size by increasing polyploidy in the syncytial skin. After discussing the evidence that led to this hypothesis, I show that polyploidization of the skin is not necessary for large body size by counter example: skin-specific depletion of CDK-2 greatly decreases organ ploidy but does not decrease body size. I propose several variables that may have confounded previous conclusions, which were based on correlational evidence, and propose an alternative model for C. elegansbody size control. Finally, I show minimal interaction between intestinal polyploidy and the TGFβ pathway.I conclude with several questions raised or left outstanding by my thesis, and propose plausible experiments to address these questions using C. elegansas a model (Chapter 4). Together, these works address a major gap in our understanding of biological scaling in multicellular systems.

Subject Added Entry-Topical Term  

Physiology.

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Cytoplasm.

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Biosynthesis.

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Genomes.

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Crop diseases.

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Yeast.

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Cell cycle.

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Protein synthesis.

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Homeostasis.

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Liver.

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Genetic engineering.

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Insects.

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Polyploidy.

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Senescence.

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Cell growth.

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Developmental biology.

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Cell division.

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Bioengineering.

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Biology.

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Cellular biology.

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Genetics.

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Plant pathology.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 86-04B.

Electronic Location and Access  

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Control Number  

joongbu:657673