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Biological oscillators are essential for processes like the cell cycle and circadian rhythms, relying on negative feedback loops and delays to create sustained oscillations. The interplay of negative and positive feedback, along with bistability, enhances the stability and robustness of these systems, as seen in examples like the p53-mdm2 feedback loop and the synthetic repressilator. Overall, these mechanisms ensure reliable oscillatory behavior critical for various biological functions.

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8 views

oscillator_assignment

Biological oscillators are essential for processes like the cell cycle and circadian rhythms, relying on negative feedback loops and delays to create sustained oscillations. The interplay of negative and positive feedback, along with bistability, enhances the stability and robustness of these systems, as seen in examples like the p53-mdm2 feedback loop and the synthetic repressilator. Overall, these mechanisms ensure reliable oscillatory behavior critical for various biological functions.

Uploaded by

gsecsportslbshall
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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How to Build a Biological Oscillator

(Varun Choudhary 20EC39040)

After delving into the chapter on biological oscillators, it's clear that these systems play a pivotal role in
various biological processes, such as the cell cycle and circadian rhythms. The foundation of any biological
oscillator lies in a negative feedback loop, which ensures that levels of a particular molecule oscillate
between high and low states. However, negative feedback alone is insuf cient to generate sustained
oscillations; it requires a delay in the feedback loop to prevent the system from simply settling into a steady
state. This delay is analogous to everyday experiences like adjusting a shower temperature, where delays in
the feedback cause repeated overshooting of the desired point, resulting in cycles of hot and cold water.

In biological systems, delays are often created by incorporating multiple components in the feedback loop.
For example, a two-component negative feedback loop can create damped oscillations if the feedback is
suf ciently strong and the timescales of the two components are closely aligned. If the timescales diverge too
much, the system becomes overdamped, and oscillations fade away. Linear stability analysis helps explain
this phenomenon by showing how the system’s eigenvalues can acquire imaginary parts, resulting in damped
oscillations.

One fascinating example of oscillatory behavior in biology is the p53-mdm2 feedback loop. Here, the protein
p53, which is crucial for DNA repair and apoptosis, regulates mdm2, and in turn, mdm2 degrades p53.
Initially, it was thought that this feedback loop would only produce damped oscillations, but experiments
revealed sustained, noise-induced oscillations. Random uctuations within the system prevent the
oscillations from damping out completely, leading to irregular pulses with noisy amplitudes but consistent
frequencies.

Biological systems often incorporate more sophisticated mechanisms to sustain oscillations. For instance,
delay oscillators, which involve feedback loops with three or more components, broaden the conditions
under which oscillations occur and reduce the need for strong feedback. A notable example is the
repressilator, a synthetic genetic circuit composed of three repressors that regulate each other in a cycle,
producing oscillatory gene expression. The repressilator demonstrates that adding more components can
increase the robustness of oscillations by expanding the range of parameters that support oscillatory
behavior.

Positive feedback also plays a crucial role in stabilizing oscillations. While negative feedback is essential for
creating oscillations, positive feedback can enhance their stability. By introducing additional delays, positive
feedback ensures that the oscillations persist over time, turning a stable system into one that oscillates
inde nitely, a concept referred to as a limit cycle.

In systems like the cell cycle, bistability, or the ability to exist in two distinct states, adds another layer of
robustness to oscillations. This feature ensures that transitions between high and low levels of critical
molecules are sharp and decisive, minimizing the impact of noise. In the case of the cell-cycle oscillator, dual
positive feedback loops help maintain reliable and consistent oscillations, which are essential for proper cell
division.

Robust bistability is critical in processes like cell-cycle regulation, where dual positive feedback loops ensure
that transitions between states are resistant to uctuations in system parameters. This dual-feedback
mechanism is conserved across various species, emphasizing its importance in biological oscillators.

To summarize, biological oscillators rely on negative feedback, delays, and cooperativity to function. Noise
can convert damped oscillations into sustained oscillations, while positive feedback and bistability enhance
stability and robustness. Many biological oscillators, such as those involved in the cell cycle, use a
combination of negative and positive feedback loops to achieve reliable oscillatory behavior, with
applications ranging from cell division to circadian rhythms.
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