東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

FindBook

Google Book

Amazon

博客來

Signaling Dynamics Shape Gene Regulation across Scales.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Signaling Dynamics Shape Gene Regulation across Scales./
作者:	Jena, Siddhartha G.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:	171 p.
附註:	Source: Dissertations Abstracts International, Volume: 83-05, Section: B.
Contained By:	Dissertations Abstracts International83-05B.
標題:	Molecular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28648079
ISBN:	9798460486441

Signaling Dynamics Shape Gene Regulation across Scales.
Jena, Siddhartha G.

Signaling Dynamics Shape Gene Regulation across Scales. - Ann Arbor : ProQuest Dissertations & Theses, 2021 - 171 p.

Source: Dissertations Abstracts International, Volume: 83-05, Section: B.

Thesis (Ph.D.)--Princeton University, 2021.

This item must not be sold to any third party vendors.

The comparison of cells to computing machines is cliched, perhaps, but at least somewhat accurate. Cells are under profound pressure to interpret information from their surroundings and current internal state, and to turn this information into actions that they must perform to stay alive. Continuing with our analogy, signaling pathways are the wires of the massive computer contained in each and every cell. Although there are a large number of signaling pathways, the realm of behaviors that any one pathway can control is enormous. Time-varying inputs, or signaling dynamics, provide a possible explanation for how one pathway may convey different types of information to a range of targets. Rather than simply be on or off in a time-invariant fashion, a pathway can exhibit pulses of rapid activation and inactivation, the frequency, duration, and amplitude of which may be all interpreted in different ways by various cellular machinery. However, if and how signaling dynamics can transmit information to cellular behavior remains largely unexplored. Here, I explore gene regulation downstream of signaling dynamics, with a primary focus on using the Ras/Erk signaling pathway as a testbed. This pathway has been studied for decades, yet only recently has been found to exhibit rapid, pulsatile dynamics in a range of systems. Elucidating the function of dynamics and how they feed forward into gene regulatory mechanisms requires the use of interdisciplinary approaches that study effects from the molecular to the population level. I first study the emergence of transcriptional heterogeneity as a function of signaling duration, amplitude, and combinatorics. Next, I use chromatin profiling to better understand how regulatory DNA responds to optogenetic pulses of signaling input. Moving to the level of population-level signaling dynamics, I leverage machine learning methods to elucidate the autonomous and coupled contributions to cell signaling, using cellular perturbations from a receptor tyrosine kinase (RTK) drug screen. Lastly, I discuss the effects that can arise when transcription factor dynamics intersect with regulatory logic in chromatin in a developing animal.

ISBN: 9798460486441Subjects--Topical Terms:

517296
Molecular biology.
Subjects--Index Terms:

Erk signaling

Signaling Dynamics Shape Gene Regulation across Scales.
LDR:03353nmm a2200385 4500 001 2349827
005 20221010063632.5
008 241004s2021 ||||||||||||||||| ||eng d
020 $a 9798460486441
035 $a (MiAaPQ)AAI28648079
035 $a AAI28648079
040 $a MiAaPQ $c MiAaPQ
100 1 $a Jena, Siddhartha G. $3 3689248
245 1 0 $a Signaling Dynamics Shape Gene Regulation across Scales.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2021
300 $a 171 p.
500 $a Source: Dissertations Abstracts International, Volume: 83-05, Section: B.
500 $a Advisor: Toettcher, Jared E.
502 $a Thesis (Ph.D.)--Princeton University, 2021.
506 $a This item must not be sold to any third party vendors.
520 $a The comparison of cells to computing machines is cliched, perhaps, but at least somewhat accurate. Cells are under profound pressure to interpret information from their surroundings and current internal state, and to turn this information into actions that they must perform to stay alive. Continuing with our analogy, signaling pathways are the wires of the massive computer contained in each and every cell. Although there are a large number of signaling pathways, the realm of behaviors that any one pathway can control is enormous. Time-varying inputs, or signaling dynamics, provide a possible explanation for how one pathway may convey different types of information to a range of targets. Rather than simply be on or off in a time-invariant fashion, a pathway can exhibit pulses of rapid activation and inactivation, the frequency, duration, and amplitude of which may be all interpreted in different ways by various cellular machinery. However, if and how signaling dynamics can transmit information to cellular behavior remains largely unexplored. Here, I explore gene regulation downstream of signaling dynamics, with a primary focus on using the Ras/Erk signaling pathway as a testbed. This pathway has been studied for decades, yet only recently has been found to exhibit rapid, pulsatile dynamics in a range of systems. Elucidating the function of dynamics and how they feed forward into gene regulatory mechanisms requires the use of interdisciplinary approaches that study effects from the molecular to the population level. I first study the emergence of transcriptional heterogeneity as a function of signaling duration, amplitude, and combinatorics. Next, I use chromatin profiling to better understand how regulatory DNA responds to optogenetic pulses of signaling input. Moving to the level of population-level signaling dynamics, I leverage machine learning methods to elucidate the autonomous and coupled contributions to cell signaling, using cellular perturbations from a receptor tyrosine kinase (RTK) drug screen. Lastly, I discuss the effects that can arise when transcription factor dynamics intersect with regulatory logic in chromatin in a developing animal.
590 $a School code: 0181.
650 4 $a Molecular biology. $3 517296
650 4 $a Developmental biology. $3 592588
650 4 $a Statistics. $3 517247
653 $a Erk signaling
653 $a Heterogeneity
653 $a Keratinocytes
653 $a Point processes
653 $a Signaling dynamics
653 $a Transcription
690 $a 0307
690 $a 0758
690 $a 0463
710 2 $a Princeton University. $b Molecular Biology. $3 2101701
773 0 $t Dissertations Abstracts International $g 83-05B.
790 $a 0181
791 $a Ph.D.
792 $a 2021
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28648079