Dynamic transcoding properties of NF-κB signaling

Mokashi, Chaitanya Sudhir (2022) Dynamic transcoding properties of NF-κB signaling. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

All biological systems constantly receive, process and respond to external signals. Cells, although being the basic unit of life, show remarkable ability to decipher the environmental cues and produce appropriate responses. This signal transduction is achieved by intricate cascades of signaling molecules which carry out the calculations needed to encode, process, decode and transfer (i.e. ‘transcode’) the external signals to responses such as various cell fate decisions. Dysregulation of cellular signal transduction is therefore the underlying cause of many diseases.
As it happens in real-time, the dynamics of both signals and the processing machinery play a crucial role in signal transduction. Microfluidic systems enable probing of signal transduction with dynamic stimuli but remain largely inaccessible. Particularly, such ability could prove useful in studying the signal processing in the NF-κB pathway, dynamics of which is pertinent to many disease pathologies. Computational approaches such as statistical and mechanistic modeling could help in formalizing the signal processing mechanisms and making useful predictions.
The overarching theme of this dissertation is to study the signal processing and control mechanisms used by cells in the context of the NF-κB signaling pathway. This includes the mechanisms and functions of specific parts of the pathway as well as their dynamics, and how they fit together to achieve the final response output. First, we develop an accessible microfluidic system to study the cellular responses to dynamic stimuli. Second, we characterize the encoding and decoding of cytokine signals in the NF-κB pathway. Third, we alter the signal encoding by leveraging the microfluidic system to maximize NF-κB responses. Finally, we consolidate our findings and put forward a framework for a comprehensive model of the NF-κB pathway.

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Details

Item Type:	University of Pittsburgh ETD
Status:	Unpublished
Creators/Authors:	Creators Email Pitt Username ORCID Mokashi, Chaitanya Sudhir csm65@pitt.edu csm65 0000-0002-8939-6958
ETD Committee:	Title Member Email Address Pitt Username ORCID Thesis Advisor Lee, Robin E.C. robinlee@pitt.edu Committee Chair Faeder, James R. faeder@pitt.edu Committee Member Chennubhotla, Chakra S. chakracs@pitt.edu Committee Member LeDuc, Philip R. prl@andrew.cmu.edu Committee Member Freyberg, Zachary Z. freyberg@pitt.edu
Date:	19 September 2022
Date Type:	Publication
Defense Date:	20 July 2022
Approval Date:	19 September 2022
Submission Date:	23 July 2022
Access Restriction:	No restriction; Release the ETD for access worldwide immediately.
Number of Pages:	160
Institution:	University of Pittsburgh
Schools and Programs:	School of Medicine > Computational Biology
Degree:	PhD - Doctor of Philosophy
Thesis Type:	Doctoral Dissertation
Refereed:	Yes
Uncontrolled Keywords:	cell signaling, microfluidics, NF-κB pathway, computational modeling, dynamic stimulation, stochastic pooling
Date Deposited:	19 Sep 2022 23:11
Last Modified:	19 Sep 2022 23:11
URI:	http://d-scholarship.pitt.edu/id/eprint/43591

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• Dynamic transcoding properties of NF-κB signaling. (deposited UNSPECIFIED)
  • Dynamic transcoding properties of NF-κB signaling. (deposited 19 Sep 2022 23:11) [Currently Displayed]

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