The research of this group is focused on the use of multi-scale computational models to study complex developmental pattern formation processes and their evolution. Within this field we specialise on the processes governing growth and patterning of the major body axis in animals and plants. Examples are the growth and segmentation of the body axis in vertebrates, arthropods and annelids and the growth of the main root and formation of lateral roots in plants. Note that both segmentation of the animal body and formation of lateral roots involves the repetitive segmentation of a growing axis, and that interesting similarities between these processes have been suggested
Our aim is to understand pattern formation in the broadest sense: from a mechanistic perspective -how exactly does the system generate a specific pattern- and from a functional and evolutionary perspective -why does the system generate a pattern in a particular manner, i.e why has this specific pattern forming mechanism evolved.
To answer the first question and understand how particular patterning processes operate we develop detailed models of developmental processes in established model organisms. In one line of research we investgate growth, convergent extension and segmentation of the body axis in the flour beetle Tribolium castaneum. Tribolium is a recently established model organism that is particularly interesting from an evolutionary developmental (evo-devo) perspective since it appears to use a segmentation mechanism that strongly resembles vertebrate segmentation. This could point to parallel convergent evolution of complex patterning mechanisms in distinct animal lineages. However, it remains unclear to what extent the patterning mechanisms really are similar, and we are actively investigating this matter. In another line of research we model growth of the main root and formation of lateral roots in the model plant Arabidopsis thaliana. Plant development differs from animal development in a number of important aspects. First, cells are encased in a cell wall, thereby preventing cell migration. As a consequence all growth and patterning in plants has to be organised from stem cell niches. Second, plants can not change their position and therefore need to flexibly adapt to changing environmental conditions. As a consequence, while animal development produces highly stereotypical bodyplans, plant development is highly plastic. In our work on plant development we investigate how stable development can be coordinated with flexible adaptation to produce robust yet adapted root architectures.
To understand from a functional and evolutionary perspective why particular pattern forming mechanisms are used we use two parallel approaches. On the one hand we compare pattern forming mechanisms found in plants and animals and try to relate similarities and differences to similarities and differences in biophysical, historical, and life history traits between plants and animals (e.g. presence versus absence of cell wall, limited embryonic growth versus continued growth, stereotypical versus plastic development). On the other hand we simulate the evolution of developmental patterning mechanisms under various conditions, investigating whether evolution repeatedly invents similar patterning processes and which factors contribute to this evolutionary channelling.
A nice example of our approach is our recent work on plant development (Mahonen et al., Nature, 2014). We discovered that plants use localised transcription combined with growth dilution and cell-cell movement to generate a gradient of the Plethora transcription factors controlling root growth and developmental zonation. This closely resembles the mechanism generating the vertebrate FGF gradient controlling axial elongation and patterning. A gradient that both controls growth and is controlled by growth has been suggested as a robust means to coordinate and scale patterning with growth, and the fact that these mechanisms evolved in parallel across kingdom strongly supports this idea. Furthermore, we discovered that while the PLT gradient instructs were cells divide, elongate and differentiate, the auxin gradient determines the rates of cell division, elongation and differentiation and that this partial division of labour is essential for combining stable developmental zonation with flexible adjustment to environmental conditions. In other words, the used mechanism is a logical evolutionary outcome considering the constraints imposed by the need for stable development and flexible adaptation in plants.
The Computational Developmental and Evolutionary Biology Group is part of Theoreotical Biology and Bioinformatics.
- Kirsten ten Tusscher, Assistant professor, Principal Investigator
- Thea van den Berg, PhD student, salt stress, lateral root priming
- Jaap Rutten, PhD student, auxin cytokinin interactions
- Daniel Weisse, postdoctoral researcher, mechanics of root growth
- Peter de Greef, Master student, phosphate starvation
- Sophia Scheper, Master student, evolution of segmentation
- Renske Vroomans, PhD student, Interplay of segmentation and convergent extension in animal axial development
- Bram van Dijk, Master student, Evolution of evolvability, genome versus network structuring
- Rutger Bos, Master student, Pro's and cons of thermodynamic models for evolutionary simulations
- Ioannis Tamvakis, Master student, Self-organised auxin patterning in plant development
- Klaartje van Berkel, PhD student, Self-organization of auxin-PIN patterning in plant development
- Jelmer de Ronde, Master student, Characterisation of the human ENCODE gene regulatory network
- Redmar van den Berg, Master student, Polymorphism and speciation in diploid genome-network models
- Janita Terpstra, Master student, Sympatric speciation in absence of assortative mating signals
- Harold Wolff, Master student, Reconciling models for planar cell polarity
We currently have a position for a PhD student:
Job description: Plants compete with neighbouring plants for sunlight. If plants sense they are being overshadowed by other plants they respond by elongating, thereby attempting to surpass these other plants and secure their access to light. While it is clear that this so-called shade avoidance response affects growth of above ground plant organs, more recent data show that also below ground plant growth is affected. These changes in shoot and root growth affect plant yield. An improved understanding of the shade-avoidance response of plants is therefore essential for the future development of crops capable of generating high yields despite being grown at high densities,
In the current project we aim to unravel how the shade avoidance response affects root growth, by investigating which signals from shoot to root may mediate this effect, and whether these signals affect root growth globally or in more local and tissue specific manner. In order to achieve this, experimental and computational approaches will be combined. The project is funded by a Building Blocks of Life NWO grant awarded to dr. K ten Tusscher (computational modeling) and prof. R. Pierik (plant photobiology) and two PhD students are being recruited.
We are now searching for a PhD student for the computational modeling. For this side of the project, detailed models for plant root growth ranging from the cellular to the whole root architecture level will be developed. These models will simulate growth, division and expansion of individual plant cells, as well as formation of lateral roots along the main root, and how these processes are controlled by genes and signalling molecules and how these change under different light conditions. The models will be based on data generated by the PhD student on the experimental side of the project, and predictions generated by the models will be used to steer future experiments.
We are looking for: For the above described project we are looking for a PhD candidate with a background in computational biology, (bio)physics, (applied) mathematics, computer science or related. He/she should have experience with programming, dynamical systems and differential equations. The candidate should have a background in biology or at least a keen interest in biological systems, and the communication skills necessary to collaborate with experimental biologists.
More info: Kirsten ten Tusscher: http://tbb.bio.uu.nl/khwjtuss/ttgroup.html/ Ronald Pierik: http://www.uu.nl/staff/RPierik/ For more information contact Kirsten ten Tusscher: email@example.com
- Developmental patterning in plants
- Adaptation in plants, gravitropism, halotropism
- Developmental patterning in animals
- Evolution of patterning networks
- Convergence and repeatability in evolution
- Evolution of species formation
- Laskowski M Ten Tusscher KH (2017).
- Periodic lateral root priming, what makes it tick.
Plant Cell pii: tpc.00638.2016.. Plant Cell.
- van den Berg T, Korver RA, Testerink CS, Ten Tusscher KH (2016).
- Modeling halotropism: A key role for root tip architecture and reflux loop remodeling in redistributing auxin.
Development , pii: dev.135111. Development.
- Vroomans RM, Hogeweg P, Ten Tusscher KH. (2016).
- In silico evo-devo: reconstructing stages in the evolution of animal segmentation.
Evodevo ,7: 14. Evodevo.
- Kazbanov I.V., Tusscher K. Panfilov A.V. (2016).
- Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism.
Sci Rep , 20835. ScientificReports.
- Vroomans R.M.A., Hogeweg P., Ten Tusscher K. (2015).
- Segment-specific adhesion as a driver for convergent extension.
PLoS Computational Biology , e1004092. PLoSCompBiol.
- Mahonen A.P., Ten Tusscher K., Siligato R., Smetana O., Diaz-Trivino S., Salojarvi J., Wachsman G., Prasad K., Heidstra R., Scheres B. (2014).
- PLETHORA gradient formation mechanism separates auxin responses.
Nature , nature13663. Nature.
- Van Berkel K., De Boer R.J., Scheres B. & Ten Tusscher K.H. (2013).
- Polar auxin transport: models and mechanisms.
Development , 140: 2253-2268. Development. DownLoad PDF.
- Ten Tusscher K.H. (2013).
- Mechanisms and constraints shaping the evolution of body plan segmentation.
Eur Phys J E Soft Matter , 36: 54. Eur Phys J E Soft Matter. DownLoad PDF.
- Ten Tusscher K.H. & Scheres B. (2011).
- Joining forces: feedback and integration in plant development.
Curr Opin Genet Dev , 21: 799-805. Curr Opin Genet Dev. DownLoad PDF.
- Ten Tusscher K.H. & Hogeweg P. (2011).
- Evolution of Networks for Body Plan Patterning; Interplay of Modularity, Robustness and Evolvability.
Plos Comp Biol , 7: e1002208. Plos Comp Biol. DownLoad PDF.
- Ten Tusscher K.H. & Hogeweg P. (2009).
- The role of genome and gene regulatory network canalization in the evolution of multi-trait polymorphisms and sympatric speciation.
BMC Evol Biol , 9: 159. BMC Evol Biol. DownLoad PDF.
- Ten Tusscher K.H.& Mourad A.& Nash M.P.& Clayton R.H.& Bradley C.P.& Paterson D.J.& Hren R.& Hayward M.& Panfilov A.V. & Taggart P. (2009).
- Organization of ventricular fibrillation in the human heart: experiments and models.
Exp Physiol , 94: 553-562. MEDLINE.
- Keldermann R.H. & Ten Tusscher K.H. & Nash M. P. & Bradley C.P & Paterson D.J & Hren R. & Hayward M. &, Panfilov A.V. & Taggart P.. (2009).
- A computational study of mother rotor VF in the human ventricles.
Am.J.Physiol. , 296: H370-H379. MEDLINE.
- Ten Tusscher K.H. & Panfilov A.V. (2008).
- Modeling of the ventricular conduction system
PBMB , 96: 152-170. PBMB. DownLoad PDF.
- Keldermann R.H. & Ten Tusscher K.H. & Nash M. P. & Hren R. & Taggart P & Panfilov A.V. (2007).
- Effect of heterogeneous APD restitution on VF organization in a model of the human ventricles
Am.J.Physiol. , 294: H764-H474. MEDLINE. DownLoad PDF.
- Ten Tusscher K.H. & Panfilov A.V. (2007).
- Influence of diffuse fibrosis on wave propagation in human ventricular
Europace , 9: vi38-vi45. Europace. DownLoad PDF.
- Ten Tusscher K.H.& Hren R. & Panfilov A.V. (2007).
- Organization of Ventricular Fibrillation in the Human Heart
Circ. Res. , 100: e87-e101. MEDLINE. DownLoad PDF.
- Ten Tusscher K.H. & Panfilov A.V. (2006).
- Cell model for efficient simulation of wave propagation in human
ventricular tissue under normal and pathological conditions.
Phys. Med.Biol., 51: 6141-6156. PMB. DownLoad PDF.
- Ten Tusscher K.H. & Panfilov A.V. (2006).
- Alternans and spiral breakup in a human ventricular tissue model.
Am.J.Physiol., 90: 326-345. MEDLINE. DownLoad PDF.
- Ten Tusscher K.H.& Bernus O.& Hren R. & Panfilov A.V. (2006).
- Comparison of electrophysiological models for human ventricular cells
Prog Biophys Mol Biol., 90: 326-345. MEDLINE. DownLoad PDF.
- Ten Tusscher K.H. & Panfilov A.V. (2005).
- Wave propagation in excitable media with randomly distributed obstacles.
Multiscale Model. Simul., 3: 265-282. DownLoad PDF.
- Ten Tusscher K.H.& Noble D.& Noble P.J. & Panfilov A.V. (2004).
- A model for human ventricular tissue.
Am.J.Physiol., 286: 1573-1589. MEDLINE. DownLoad PDF.
- Ten Tusscher K.H. & Panfilov A.V. (2004).
- Eikonal formulation of the minimal principle for scroll wave
Phys. Rev. Lett, 93: 108106. MEDLINE. DownLoad PDF.
- Ten Tusscher K.H. & Panfilov A.V. (2003).
- Influence of nonexcitable cells on spiral breakup in two-dimensional
and three-dimensional excitable media.
Phys Rev E Stat Nonlin Soft Matter Phys., 68: 062902. MEDLINE. DownLoad PDF.
- Ten Tusscher K.H. & Panfilov A.V. (2003).
- Reentry in heterogeneous cardiac tissue described by the Luo-Rudy
ventricular action potential model.
Am.J.Physiol., 284: H542-H548. MEDLINE. DownLoad PDF.