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Memory and Decoding in Signaling Transduction Pathways


Kim, Kibeom (2019) Memory and Decoding in Signaling Transduction Pathways. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/BJDQ-JX45.


Intercellular communication allows cells to broadcast and receive necessary information for decision making, and is essential for development, growth, and maintenance of a community of cells in a multicellular organism. Signaling pathways are highly conserved systems of communication between cells, each composed of a distinct network of protein interactions that detect extracellular signal and transduce the signal information for cellular response. A signaling pathway typically encodes information from signaling events into dynamics of second messengers, intracellular molecules in the signaling pathway that activate in response to signal and initiate cellular response. Therefore, understanding how information is encoded in second messenger dynamics, and how transcriptional machinery decode and generate output response is an important aspect in investigating how signaling information is transduced inside a cell. In the first chapter, we investigate the timescales of memory in endogenous β-catenin and Smad3, second messengers in the Wnt and Tgf-β pathways, through single cell timelapse microscopy. The findings demonstrate that both second messengers have short memory and high cell-to-cell variability, and that their memory is tunable through modulating cellular contexts. In the second chapter, we investigate decoding of information from β-catenin in the Wnt pathway. We identify a novel 11-bp DNA element that recruit β-catenin for transcriptional suppression. This negative regulatory element is shown to act in conjunction with the canonical Wnt responsive element to form an incoherent feedforward loop (IFFL). Through mathematical simulations, we present how the IFFL circuit can generate complex output functions in decoding β-catenin dynamics, which include those that confer robustness against perturbations in signaling response such as band-pass filtering and fold change detection.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:signaling pathways, wnt pathway, signal transduction, transcriptional regulation, memory
Degree Grantor:California Institute of Technology
Division:Biology and Biological Engineering
Major Option:Systems Biology
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Goentoro, Lea A.
Thesis Committee:
  • Elowitz, Michael B. (chair)
  • Hay, Bruce A.
  • Goentoro, Lea A.
  • Zinn, Kai George
Defense Date:23 May 2019
Record Number:CaltechTHESIS:06092019-220453694
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for Ch. 3.
Kim, Kibeom0000-0002-0764-4875
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11730
Deposited By: Kibeom Kim
Deposited On:11 Jun 2019 18:38
Last Modified:04 Oct 2019 00:26

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