Bistability of PP2A-B55 and APC/C activity
In a collaboration with Julia Kamenz in the lab of Jim Ferrell at Stanford Univ., we demonstrate biochemically using Xenopus laevis egg extracts that the Cdk1-counteracting phosphatase PP2A-B55 and the APC/C function as a bistable switch, even when the bistability of Cdk1 activation is suppressed. In addition, Cdk1 regulates PP2A-B55 in a biphasic manner and APC. Our findings, which are published in Current Biology, suggest that changes in Cdk1 activity are permissive for mitotic entry and exit but that the changes in PP2A-B55 activity are the ultimate trigger. Very impressive experiments by Julia, who just started her own lab at the university of Groningen in the Netherlands, check it out: https://www.rug.nl/staff/j.l.kamenz/.
Time-dependent bistable switches enhance robustness and accuracy of cell cycle transitions
Jan showed how a dynamically changing bistable switch can provide a cell with better control over the timing of cell cycle transitions. Moreover, cell cycle oscillations built on bistable switches are more robust when the bistability is modulated in time. These findings are not specific to cell cycle models and may apply to other bistable systems in which the bistable response curve is time-dependent. Read all about this work in PLoS Computational Biology. Well done Jan!
So happy to welcome Daniel to our lab! During his PhD at the Institute for Cross-Disciplinary Physics and Complex Systems (IFISC - Spain), he worked on vegetation models of pattern formation. He will use techniques from statistical physics and nonlinear dynamics to study pattern formation processes in the context of the cell cycle.
Jan analyzed how pacemaker-generated waves synchronize an oscillatory medium
Jan used numerical simulation to study the properties of waves in oscillatory media sent out by a pacemaker. By comparing different oscillator types and pacemaker properties, he quantified which factors determine the speed of these waves, which are often used by biological systems to transmit information and synchronize processes. The work is now out in Phys. Rev. Research, congratulations!
Talks at Dynamics Days Digital
Although the in-person conference of Dynamics Days was canceled due to the pandemic, an online version was organized (see the conference's website). Jan and Felix presented their work on pacemaker-driven mitotic waves in a minisymposium on “Nonlinear waves in biology” organized by Lendert and Carsten Beta (Univ. Potsdam). You can find their talks on Youtube: Felix' talk and Jan's talk.
Stefan successfully defended his thesis work
On July 8, Stefan defended his thesis entitled “Dynamical analysis of nutrient-explicit models for small microbial communities”, a collaboration with Prof. Didier Gonze at the Unit of Theoretical Chronobiology (ULB), and Prof. Jan Danckaert at the Applied Physics research group (APHY, VUB). Stefan did a great job at clearly explaining his research. We wish him all the best in his further career and he will be missed in the group!
How do oscillatory systems with multiple pacemakers synchronize their dynamics?
Felix and Jan have studied what happens when multiple pacemakers compete with each other. Using numerical simulations in a generic reaction-diffusion system, they determined when and how pacemakers synchronize depending on their size, oscillation frequency, and type of coupling. Their work has been published in Chaos. Well done Felix and Jan!
Nuclei determine the spatial origin of mitotic waves
We show how mitotic waves initiate at pacemakers, regions which oscillate faster than their surroundings. In cell-free extracts of Xenopus laevis eggs, we find that nuclei define such pacemakers by concentrating cell cycle regulators. While Felix developed computational models to illustrate how multiple nuclei can collectively determine the pacemaker location, the experiments were carried out by Alexandra, Arno and Liliana. Our work provides insight into how nuclei and spatial system dimensions can control local concentrations of regulators, influencing the emergent behavior of mitotic waves. For more information, see the publication in eLife. Congratulations to everyone for this great team effort!
Mutualistic cross-feeding in microbial systems generates bistability via an Allee effect
Congratulations to Stefan for publishing his latest work in Scientific Reports! In microbial ecosystems, species can interact in a mutualistic way as a result of metabolic cross-feeding. Here, we reduce a theoretical nutrient-explicit model of two mutualistic cross-feeders in a chemostat, uncovering an explicit relation to a growth model with an Allee effect.
The antagonistic RepoMan:Aurora-B pair is co-regulated in proliferating cells
In collaboration with the Bollen lab in our department, we have shown that the abundance of RepoMan, an important phosphatase scaffold, is regulated by the same mechanisms that control the kinase Aurora B. Using experimental and numerical work, we demonstrate that the co–up-regulation of RepoMan and Aurora B is associated with tumor aggressiveness, but it also exposes a vulnerable target for therapeutic intervention. Congratulations to Maria Giulia of the Bollen lab who did all the experimental work and Jan for his numerical contributions! For more information, see our article in MBoC.