Measurement and maintenance of human cell size

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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
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
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
Genre Text

Bibliographic information

Statement of responsibility Daniel Fischbein Berenson.
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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