Measurement and maintenance of human cell size
Abstract/Contents
- Abstract
- How cells reach and maintain the right size is a longstanding question in biology. Moreover, the many ways in which cell size may influence cellular physiology have received insufficient attention. Research has been hindered by inadequate tools for measuring size in living cells. In this dissertation, a novel strategy is developed to measure the size of single human cells using a nuclear-localized fluorescent protein expressed from a constitutive promoter. This method is validated by comparing it to established alternatives, with the result that the fluorescence measurements are more robust and less dependent on image segmentation than the commonly-used measurement of nuclear volume. Then, this strategy is applied to understand the size dependence of a crucial part of the cell cycle -- the transition from G1 to S phase -- and how it contributes to cell size homeostasis. One hypothesis is that titration of a size-proportional factor against a size-independent molecular factor could function as a "molecular ruler" to create a size-dependent biochemical signal. Several cell cycle regulatory proteins are tested as candidates and it is observed that one of them, the retinoblastoma protein Rb, is unique in its size-nonscaling behavior: Rb is diluted during G1 phase. This property of Rb is a consequence of its synthesis, partitioning, and degradation pattern. Finally, it is demonstrated that Rb concentration is a size-dependent determinant of cell cycle progression. Future areas of inquiry include the phenomenology of cell growth, mechanisms of size scaling, and in vivo size homeostasis.
Description
Type of resource | text |
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Form | electronic resource; remote; computer; online resource |
Extent | 1 online resource. |
Place | California |
Place | [Stanford, California] |
Publisher | [Stanford University] |
Copyright date | 2019; ©2019 |
Publication date | 2019; 2019 |
Issuance | monographic |
Language | English |
Creators/Contributors
Author | Berenson, Daniel Fischbein |
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Degree supervisor | Skotheim, Jan, 1977- |
Thesis advisor | Skotheim, Jan, 1977- |
Thesis advisor | Cyert, Martha S, 1958- |
Thesis advisor | Dixon, Scott |
Thesis advisor | Lipsick, Joseph Steven, 1955- |
Degree committee member | Cyert, Martha S, 1958- |
Degree committee member | Dixon, Scott |
Degree committee member | Lipsick, Joseph Steven, 1955- |
Associated with | Stanford University, Department of Biology. |
Subjects
Genre | Theses |
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Genre | Text |
Bibliographic information
Statement of responsibility | Daniel Fischbein Berenson. |
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Note | Submitted to the Department of Biology. |
Thesis | Thesis Ph.D. Stanford University 2019. |
Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Daniel Fischbein Berenson
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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