Felix successfully defended his PhD
Felix convincingly presented his PhD work entitled “Mathematical modeling of nuclei as pacemakers of cell cycle oscillations”. It was a wonderful day and evening, celebrating Felix's achievements of the last few years. We wish Felix all the best in his new position teaching at the university in Antwerp. As he won't be far away, we hope to still see you regularly here. Congratulations Dr. Nolet!
Jolan successfully defended his PhD
In the context of a joint PhD with Prof. Verfaillie of the Stem Cell institute, Jolan presented his PhD work entitled “On the study of cellular proliferation and differentiation: From experiment to theory”. Many thanks to everyone in the jury, being Georg Halder, Hans Van Oosterwyck, Leo van Grunsven, and Julia Kamenz. Everyone agreed that Jolan did an excellent job and were particularly impressed with his to-the-point and in-depth knowledge of both experimental and theoretical work. Similarly impressed here Jolan!
A modular approach for modeling the cell cycle based on functional response curves
Bistability plays an important role in many biochemical processes and typically emerges from complex interaction patterns such as positive and double negative feedback loops. Jolan and Jan explicitly incorporated a functional expression describing an S-shaped input-output curve in the model equations, without the need for considering the underlying biochemical events. Using such approach, we then constructed a cell cycle model consisting of multiple bistable switches, accounting for a number of known properties of the cell cycle. Nice work Jolan and Jan! Read more here in our PLoS Comp. Biol. paper.
Analytical approximations for the speed of pacemaker-generated waves
In oscillatory media, waves can be generated by pacemaker regions which oscillate faster than their surroundings. Jan applied analytical tools (i.e. singular perturbation and phase reduction methods) to investigate the factors that determine the speed of these waves. These analytical estimates are compared to numerical simulations described in our previous work. Check out the paper in Phys. Rev. E. Good stuff Jan!
How do nuclei control mitotic waves in an import-diffusion model?
In this work, Felix extended the modeling work he did for our 2020 eLife paper in which we showed that nuclei control the spatial origin of mitotic waves. He analyzed a model where nuclei periodically import and export cell cycle regulators, leading to a redistribution of such regulator in the cytoplasm. We show that when the cell cycle period depends on the local concentration of regulators, the model exhibits mitotic waves. Congratulations Felix! Read more here.
Jan successfully defended his PhD
At the castle of Arenberg, Jan gave a wonderful presentation about his thesis work, entitled “The role of bistability and time delay in the coordination of the cell cycle”. Although many followed his PhD defense online, it was a pleasure to be able to have some family and friends present for this important occasion. Also a big thanks to all jury members: Jordi Garcia Ojalvo, Edda Klipp, Karel Talavera and Enrico Carlon!
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.
We’re excited to have Liliana as a new member of the lab! Liliana will be doing experimental work to figure out how self-organization processes can play an important role in ensuring proper cell cycle progression.
Jan publishes review on traveling fronts in systems with a time delay
In a collaboration with Thomas Erneux (ULB), Jan has published a paper in which we review a series of key traveling front problems in reaction–diffusion systems with time-delayed feedback, appearing in ecology, nonlinear optics and neurobiology. This work is part of the theme issue ‘Nonlinear dynamics of delay systems’ in Philosophical Transactions of the Royal Society A.
Jan explains his research in a video
The project "Wetenschap Uitgedokterd" aims to get young scientists to leave their comfort zone in the lab and puts them in front of a camera to clearly explain their research to the general public in 3 minutes. Watch Jan's video here (only in Dutch). Well done Jan, crystal clear!
Alexandra starts a new challenge at the FWO
After almost 3 years together, Alexandra is leaving the lab to reinforce the Research Foundation - Flanders focussing on research policies and strategies concerning fundamental research. As the first member of the group, Alexandra played a crucial role in setting up the lab from the very beginning and was a wonderful person to have around. We wish her all the best and she will be greatly missed in the lab!
Eternal sunshine of the spotless cycle?
In a recent study, Purvis and colleagues (Chao et al, 2019) quantify cell cycle phase durations in human cells and propose a model whereby cell cycle progression in single cells is a succession of uncoupled, memoryless phases, each composed of a characteristic rate and number of steps. They also suggest that having such memoryless phases is a feature of healthy cells, while cancer cells have correlated phases. Silvia Santos (Crick, London) and Lendert have written a News&Views piece about this article.
Do biological timers and sensors work together to coordinate processes in cell signaling?
In a perspective piece in BioEssays, Junbin Qian, Mathieu Bollen, and Lendert argue that this is indeed the case. Recent data suggest that timers and sensors can work together to guarantee correct timing and responsiveness. By exploring examples of cellular stress signaling from mitosis, DNA damage, and hypoxia, we discuss the common architecture of timer‐sensor integration, and how its added features contribute to the generation of desired signaling profiles when dealing with stresses of variable duration and strength.
Pedro reports on how quadratic soliton combs are formed in Optics Letters
In a joint effort with Tobias Hansson, Stefan Wabnitz, and François Leo, Pedro investigated theoretically the dynamics of quadratic frequency combs in a dispersive second-harmonic generation cavity system. We identified different dynamical regimes and demonstrated that the same system can exhibit both bright and dark localized cavity solitons in the absence of a temporal walk-off. These results are published in two Optics Letters papers, see here and here.
Stefan’s joint work with the Raes and De Vuyst lab has been published in eLife
In a collaboration with the lab of Jeroen Raes (KUL) and Luc De Vuyst (VUB), Stefan has helped exploring human gut community dynamics. We established a synthetic community composed of three representative human gut isolates (Roseburia intestinalis L1-82, Faecalibacterium prausnitzii A2-165 and Blautia hydrogenotrophica S5a33) and explored their interactions under well-controlled conditions in vitro. Using a mechanistic model as reference, we demonstrated that strains grown in co-culture behaved differently than those in mono-culture and confirmed their altered behavior at the transcriptional level. For more information, see the publication in eLife.
We're happy to welcome Arno to our lab! Arno studied biosystems engineering and he will be designing and using microfluidic devices to study various aspects of the spatiotemporal regulation of the cell cycle.
Stefan and Alexandra show how excitability can lie at the heart of toxin excitations in bacteria
Toxin-antitoxin (TA) systems in bacteria and archaea are small genetic elements consisting of the genes coding for an intracellular toxin and an antitoxin that can neutralize this toxin. In various cases, the toxins cleave the mRNA. Stefan and Alexandra have used deterministic and stochastic modeling to explain how toxin-induced cleavage of mRNA in TA systems can lead to excitability, allowing large transient spikes in toxin levels to be triggered. This work has been published in PLoS One .
Stefan publishes work on the dynamics of two interacting microbial species in the chemostat
In the context of Stefan’s joint PhD at the ULB (with D. Gonze) and VUB (with J. Danckaert) in Brussels, he has theoretically studied the dynamics of two interacting microbial species in the chemostat. These species are competitors for a common resource, as well as mutualists due to cross-feeding. He demonstrated that this system has a rich repertoire of dynamical behavior, including bistability, and showed that the different steady state solutions can be well captured by an extended Lotka-Volterra model. This work was published in PLoS One.
Pedro publishes detailed bifurcation study of localized light pulses in optical resonators
Pedro has studied the origin, stability, and bifurcation structure of different types of bright localized structures described by the Lugiato-Lefever equation. This mean field model describes the nonlinear dynamics of light circulating in fiber cavities and microresonators. In this work, published in Phys. Rev. E , we show how the organization (bifurcation structure) of these localized light patterns critically changes as one increases the cavity detuning, one of the important experimental control parameters in the system.
Commentary on the function of dynamic phosphorylation-dephosphorylation cycles published in Dev. Cell
Adrian Saurin (Dundee Univ.) and Lendert have written a commentary on the potential roles of dynamic phosphorylation-dephosphorylation cycles. They discuss how rapid cycles could underlie important signaling properties, including the ability to rapidly bind and release proteins.
Work on delay models for the embryonic cell cycle published in PLoS One
Jan's work on delay models for the early embryonic cell cycle oscillator has been published in PLoS One . We showed that different implementations of the time delay can have a large impact on the resulting oscillation, exploring a fixed time delay, a distribution of time delays, and a delay that is state-dependent. Well done Jan and Alexandra!
Lendert elected member of Young Academy
Lendert has been elected member of the Young Academy, part of the Royal Flemish Academy of Belgium for Science and the Arts (KVAB). On February 6, the Young Academy celebrated their five year anniversary and twelve new members were inaugurated with speeches by Prof. Robbert Dijkgraaf and the King of Belgium (http://jongeacademie.be/5-jaar-jonge-academie/). The Young Academy is an interuniversity and interdisciplinary meeting place for scientists and artists to work on initiatives related to e.g. science communication, policy, and education.
Publication with Moll lab in Nucleic Acids Research
In a collaboration with Nela Nikolic from Isabella Moll's lab at the University of Vienna, we have studied how growth heterogeneity in bacterial populations is modified by the ability of toxins to sequence-specifically cleave single-stranded RNA upon various stressful conditions. We focused on the situation where such toxins can be activated as a part of the mazEF toxin–antitoxin module in Escherichia coli. Congratulations to Nela and all co-authors for reporting on this work in Nucleic Acids Research!
Publication with Bollen lab in Molecular Cell
Congratulations to Junbin of the Bollen lab who just published his research in Molecular Cell. In collaboration with our lab, Junbin showed that there exists a transient phosphorylation signal (BUB1-T461ph) that plays a crucial role in correctly activating the mitotic checkpoint. This novel biochemical timer activates the checkpoint independently of the microtubule-kinetochore attachment status, and we show that disrupting this BUB1 timer holds therapeutic potential by targeting cancer cells. The paper was featured on the KU Leuven news.
Welcome Nadja and Felix
A warm welcome to Nadja D'Uonno and Felix Nolet, who just joined the lab! Their respective PhD projects will focus on experimentally investigating the influence of temperature on cell division timing, and developing theoretical models to describe the spatial regulation of cell cycle processes.
Review article published in Trends in Cell Biology
Adrian Saurin (Dundee, UK), Junbin Qian, Mathieu Bollen (LBT lab in our department), and Lendert have written a review article in Trends in Cell Biology on how interacting kinases and phosphatases control mitotic processes in space and time.
Lab organizes workshop for Children’s University
Alexandra, Jan and Lendert organized a workshop at the Children University event of KU Leuven. Several groups of children in primary school (8-12 years old) visited the university and they played several games in which they learned how more complex patterns can emerge from simple rules. The picture shows the kids applying one of Wolfram's cellular automata rules using two-color cardboards.
Jan wins poster award at departmental mixer
Jan won the best poster award at our local departmental mixer event. Here, PhD students present their work, which aims at increasing interaction between the 14 research labs in our department. Well done Jan and enjoy the goodies that you got!
“Desynchronizing embryonic cell division waves reveals the robustness of Xenopus laevis development” on the cover of Cell Reports
Joint work with Graham Anderson from Jim Ferrell's lab just got published in Cell Reports and featured on the cover. In this work, we applied strong temperature differences across young frog embryos to desynchronize the regular cell division timing. We found that all cells behave as independent oscillators. Moreover, we saw that although mesoderm induction becomes abnormal initially, the embryos are still able to get their development back on track.
New fellowships and postdoc grants for the lab
Jan and Jolan both received a FWO doctoral fellowship to pursue their research these next 4 years, while Alexandra and Pedro received a one-year postdoctoral grant from KU Leuven. Pedro was also awarded a three year grant from the FNRS. So happy for everyone and proud to have such talented researchers in the lab!
Stefan won the best poster award at the “Crossroads in complex systems” conference
From June 5-8, the IFISC institute (Institute for Cross-Disciplinary Physics and Complex Systems - UIB-CSIC, Spain) celebrated their 10th anniversary by organizing the conference "Crossroads in Complex Systems". This wonderful meeting ended on a high with Stefan winning the best poster award for his work "Modeling the dynamics of a small community of interacting human colon bacteria", congratulations Stefan!
Pedro publishes work on interacting bright and dark solitons in PRA and EPJD
Pedro successfully defended his PhD thesis
On March 3, Pedro successfully defended his PhD thesis entitled "Dynamics of dissipative localized structures in driven nonlinear optical cavities". You can find a copy of his thesis here. Excellent work Pedro!
Pedro published his work on a new excitability mechanism
Pedro published a paper in Physical Review E as a Rapid Communication, in which he reports on a new mechanism for excitability in extended systems without underlying oscillatory dynamics. Well done Pedro!
Alexandra’s PhD work got published and selected as a breakthrough article
Julen joins the lab
On Dec 14, Julen Gelens La Greca was born. Being by far the youngest and cutest member, he has a courtesy appointment in the lab as mascotte and frog whisperer.
Jan joins the lab
Jan has joined the lab and will be studying the coordination of biological processes (i.e. the cell cycle) from a more mathematical point of view. Glad to have you in the group!
Alexandra joins the lab
Welcome to the lab Alexandra, congratz on a great PhD thesis and we're very happy to have you on board to help exploring the regulation of cell cycle processes.
Goodbye Ferrell lab
Goodbye Ferrell lab, Stanford, and California, you were absolutely great and will be missed!
Lendert officially starts the lab "Dynamics in Biological Systems" at the department of Cellular and Molecular Medicine, KU Leuven. He will, however, still stay half a year longer at the Ferrell lab at Stanford University to finish ongoing projects.