11am - 12 noon BST

Monday 15 August 2022

Noise-induced transitions in gene expression and a novel and robust molecular switch actuating the quantitative model of eukaryotic cell cycle control


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This event will feature two talks:

Noise-induced transitions in gene expression

Speaker: Dr Andrea Rocco, University of Surrey

Noise-induced transitions have been largely investigated in a variety of chemical, physical, and biological systems. These may occur when the system is affected by so-called extrinsic noise, representing for instance a fluctuating environment. Extrinsic noise can produce highly non-trivial effects, such as the ‘creation’ of stable states, and can lead to the emergence of multistability or oscillatory behaviours in systems deterministically monostable.

In this talk, I will review two fundamentally different mechanisms that have been identified to account for the emergence of noise-induced transitions. The first one is a consequence of the noise being linear, Gaussian, and “white”, namely characterized by fast fluctuations. The second mechanism, usually referred to as “nonlinear noise filtering”, is instead based on the noise being very slow, non-Gaussian, and nonlinear. I will propose some recent results obtained in my group, which provide a dynamical derivation of the noise filtering approach, and are based on a perturbative time-scale expansion of the relevant dynamics.

I will illustrate these different mechanisms by using the repressed gene as a simple but fundamental model of gene regulation, and highlight that the emergence of noise-induced transitions appears to be strongly dependent on the type of noise adopted, and on the degree of nonlinearity present in the system.

Finally, I will comment on possible evolutionary implications of these results.

A novel and robust molecular switch actuating the quantitative model of eukaryotic cell cycle control

Speaker: Dr Matteo Barberis, University of Surrey

The eukaryotic cell cycle is driven by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with a timely pattern called “waves of cyclins”. This pattern guarantees coordination and alternation of DNA synthesis with cell division, and its failure results in altered cyclin/Cdk dynamics and abnormal cell proliferation. Although details about transcription of cyclins are available, the network motifs responsible for this timely pattern are currently unknown.

Here I show a novel principle of design that ensures cell cycle time keeping through interlocking transcription with cyclin/Cdk dynamics in budding yeast. Through analyses of kinetic models of the cyclin/Cdk network and quantitative data of Clb dynamics, a novel regulatory design is unravelled that highlights the Clb/Cdk–TF axis being pivotal for timely cell cycle dynamics. This work rationalizes the quantitative model of Cdk control proposed by the 2001 Nobel Prize recipient Sir Paul Nurse, identifying regulatory motifs underlying cell proliferation dynamics in eukaryotes.