Real-Time Genetic Compensation Defines the Dynamic Demands of Feedback Control.
Cell
; 175(3): 877-886.e10, 2018 10 18.
Article
in En
| MEDLINE
| ID: mdl-30340045
ABSTRACT
Biological signaling networks use feedback control to dynamically adjust their operation in real time. Traditional static genetic methods such as gene knockouts or rescue experiments can often identify the existence of feedback interactions but are unable to determine what feedback dynamics are required. Here, we implement a new strategy, closed-loop optogenetic compensation (CLOC), to address this problem. Using a custom-built hardware and software infrastructure, CLOC monitors, in real time, the output of a pathway deleted for a feedback regulator. A minimal model uses these measurements to calculate and deliver-on the fly-an optogenetically enabled transcriptional input designed to compensate for the effects of the feedback deletion. Application of CLOC to the yeast pheromone response pathway revealed surprisingly distinct dynamic requirements for three well-studied feedback regulators. CLOC, a marriage of control theory and traditional genetics, presents a broadly applicable methodology for defining the dynamic function of biological feedback regulators.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Gene Expression Regulation, Fungal
/
Feedback, Physiological
/
Optogenetics
Type of study:
Prognostic_studies
Language:
En
Year:
2018
Type:
Article