본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

Proceedings of the National Academy of Sciences of the United States of America v.114 no.4, 2017년, pp.693 - 698   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

First-passage time approach to controlling noise in the timing of intracellular events

Ghusinga, Khem Raj (Department of Electrical and Computer Engineering, University of Delaware, Newark, DE 19716 ) ; Dennehy, John J. (The Graduate Center, City University of New York, New York, NY 10016 ) ; Singh, Abhyudai (Department of Electrical and Computer Engineering, University of Delaware, Newark, DE 19716; ) ;
  • 초록  

    Significance Understanding how randomness in the timing of intracellular events is buffered has important consequences for diverse cellular processes, where precision is required for proper functioning. To investigate event timing in noisy biochemical systems, we develop a first-passage time framework in which an event is triggered when a regulatory protein accumulates up to a critical level. Formulas quantifying event-timing fluctuations in stochastic models of protein synthesis with feedback regulation are developed. Formulas shed counterintuitive insights into regulatory mechanisms essential for scheduling an event at a precise time with minimal fluctuations. These results uncover various features in the biochemical pathways used by phages to lyse individually infected bacterial cells at an optimal time, despite stochastic expression of lysis proteins. In the noisy cellular environment, gene products are subject to inherent random fluctuations in copy numbers over time. How cells ensure precision in the timing of key intracellular events despite such stochasticity is an intriguing fundamental problem. We formulate event timing as a first-passage time problem, where an event is triggered when the level of a protein crosses a critical threshold for the first time. Analytical calculations are performed for the first-passage time distribution in stochastic models of gene expression. Derivation of these formulas motivates an interesting question: Is there an optimal feedback strategy to regulate the synthesis of a protein to ensure that an event will occur at a precise time, while minimizing deviations or noise about the mean? Counterintuitively, results show that for a stable long-lived protein, the optimal strategy is to express the protein at a constant rate without any feedback regulation, and any form of feedback (positive, negative, or any combination of them) will always amplify noise in event timing. In contrast, a positive feedback mechanism provides the highest precision in timing for an unstable protein. These theoretical results explain recent experimental observations of single-cell lysis times in bacteriophage [Formula]. Here, lysis of an infected bacterial cell is orchestrated by the expression and accumulation of a stable [Formula] protein up to a threshold, and precision in timing is achieved via feedforward rather than feedback control. Our results have broad implications for diverse cellular processes that rely on precise temporal triggering of events.


  • 주제어

    first-passage time .   event timing .   stochastic gene expression .   feedback control .   single cell.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
유료다운로드

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기