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A spatio-temporal model to reveal oscillator phenotypes in molecular clocks: Parameter estimation elucidates circadian gene transcription dynamics in single-cells

September 24, 2021 @ 1:00 pm - 2:00 pm KST

B305 Seminar room, IBS, 55 Expo-ro Yuseong-gu
Daejeon, 34126 Korea, Republic of
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Speaker

Seokjoo Chae
KAIST

We will discuss about “A spatio-temporal model to reveal oscillator phenotypes in molecular clocks: Parameter estimation elucidates circadian gene transcription dynamics in single-cells”, Unosson et al., bioRxiv, 2021

We propose a stochastic distributed delay model together with a Markov random field prior and a measurement model for bioluminescence-reporting to analyse spatiotemporal gene expression in intact networks of cells. The model describes the oscillating time evolution of molecular mRNA counts through a negative transcriptional-translational feedback loop encoded in a chemical Langevin equation with a probabilistic delay distribution. The model is extended spatially by means of a multiplicative random effects model with a first order Markov random field prior distribution. Our methodology effectively separates intrinsic molecular noise, measurement noise, and extrinsic noise and phenotypic variation driving cell heterogeneity, while being amenable to parameter identification and inference. Based on the single-cell model we propose a novel computational stability analysis that allows us to infer two key characteristics, namely the robustness of the oscillations, i.e. whether the reaction network exhibits sustained or damped oscillations, and the profile of the regulation, i.e. whether the inhibition occurs over time in a more distributed versus a more direct manner, which affects the cells’ ability to phase-shift to new schedules. We show how insight into the spatio-temporal characteristics of the circadian feedback loop in the suprachiasmatic nucleus (SCN) can be gained by applying the methodology to bioluminescence-reported expression of the circadian core clock gene Cry1 across mouse SCN tissue. We find that while (almost) all SCN neurons exhibit robust cell-autonomous oscillations, the parameters that are associated with the regulatory transcription profile give rise to a spatial division of the tissue between the central region whose oscillations are resilient to perturbation in the sense that they maintain a high degree of synchronicity, and the dorsal region which appears to phase shift in a more diversified way as a response to large perturbations and thus could be more amenable to entrainment.

Details

Date:
September 24, 2021
Time:
1:00 pm - 2:00 pm KST
Event Category:

Organizer

Jae Kyoung Kim
Email
jaekkim@kaist.ac.kr

Venue

B305 Seminar room, IBS
55 Expo-ro Yuseong-gu
Daejeon, 34126 Korea, Republic of
+ Google Map
IBS 의생명수학그룹 Biomedical Mathematics Group
기초과학연구원 수리및계산과학연구단 의생명수학그룹
대전 유성구 엑스포로 55 (우) 34126
IBS Biomedical Mathematics Group (BIMAG)
Institute for Basic Science (IBS)
55 Expo-ro Yuseong-gu Daejeon 34126 South Korea
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