NDLI: Optimal auto-regulation to minimize first-passage time variability in protein level

Content Provider	IEEE Xplore Digital Library
Author	Ghusinga, K.R. Pak-Wing Fok Singh, A.
Copyright Year	2015
Description	Author affiliation: Fac. of Math. Sci., Univ. of Delaware, Newark, DE, USA (Pak-Wing Fok; Singh, A.) \|\| Dept. of Electr. Eng., Univ. of Delaware, Newark, DE, USA (Ghusinga, K.R.)
Abstract	The timing of cellular events is inherently random because of the probabilistic nature of gene expression. Yet cells manage to have precise timing of important events. Here, we study how gene expression could possibly be regulated to precisely schedule timing of an event around a given time. Event timing is modeled as the first-passage time (FPT) for a protein's level to cross a critical threshold. Considering auto-regulation as a possible regulatory mechanism, we investigate what form of auto-regulation would lead to minimum stochasticity in FPT around a fixed time. We formulate a stochastic gene expression model and show that under certain assumptions, it reduces to a birth-death process. Our results show that when the death rate is zero, the objective is best achieved when all of the birth rates are equal. On the contrary, when the death rate is non-zero, the optimal birth rates are not equal. In terms of the gene expression model, these results illustrate that when protein does not degrade, stochasticity in FPT around a given time is minimized when there is no auto-regulation of its expression. However, when the protein degrades, some form of auto-regulation is required to achieve this. These results are consistent with experimental findings for the lysis time stochasticity in λ phage.
Starting Page	4411
Ending Page	4416
File Size	480379
Page Count	6
File Format	PDF
e-ISBN	9781479986842
DOI	10.1109/ACC.2015.7172023
Language	English
Publisher	Institute of Electrical and Electronics Engineers, Inc. (IEEE)
Publisher Date	2015-07-01
Publisher Place	USA
Access Restriction	Subscribed
Rights Holder	American Automatic Control Council(AACC)
Subject Keyword	Proteins Gene expression Mathematical model Protein engineering Linear programming Timing Degradation
Content Type	Text
Resource Type	Article

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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