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How Retroactivity Affects the Behavior of Incoherent Feedforward Loops
Junmin Wang1, Calin Belta1, Samuel A Isaacson2
1The Bioinformatics Graduate Program, Boston University, Boston, MA 02215, USA.
Iscience
|December 11, 2020
Summary
Incoherent feedforward loops (IFFLs) can surprisingly benefit from high retroactivity, unlike negative autoregulated circuits. This flexibility may explain their prevalence in biological networks.
Area of Science:
- Systems biology
- Gene regulatory networks
- Biophysics
Background:
- Incoherent feedforward loops (IFFLs) are common network motifs.
- IFFLs are known for accelerating responses and generating pulses.
- The impact of high retroactivity on IFFL behavior is not well understood.
Purpose of the Study:
- To investigate the behavior of IFFLs under varying levels of retroactivity.
- To compare IFFL responses to those of negative autoregulated circuits.
- To explore the potential of retroactivity in synthetic biology design.
Main Methods:
- Simulation of ordinary differential equation (ODE) models.
- Comparison of IFFLs with varying degrees of retroactivity.
- Analysis of network response time and pulse amplitude.
Main Results:
- Increasing retroactivity in IFFLs can alter response time and pulse amplitude in complex ways (increase, decrease, or no change).
- In contrast, increased retroactivity consistently slows down negative autoregulated circuits.
- IFFLs demonstrate a unique adaptability to retroactivity.
Conclusions:
- Retroactivity, often seen as a design challenge, can be leveraged to enhance IFFL performance.
- The adaptable nature of IFFLs in handling retroactivity may contribute to their widespread occurrence in biological systems.
- Findings suggest new avenues for designing robust synthetic gene circuits.
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