Theoretical Biology & Bioinformatics

tree of life
Kirsten ten Tusscher

Kirsten ten Tusscher

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Research

The research of the Ten Tusscher group focuses on the deciphering of developmental patterning processes in both plants and animals. For this the group uses state-of-the-art multi-scale modeling approaches and closely collaborates with experimental research labs. Our current research encompasses several major research lines:

  • Plant root directional growth in response to saline environments
  • Plant root decision making in response to heterogeneous nitrate
  • Overall plant responses to drought and high temperature stress
  • Mechanisms of earliest stages of lateral root formation
  • Evo devo of root patterning and LR formation
  • Regulatory networks controlling cell fate decisions

Plant root development


Unlike animals, plants keep growing and generating new organs throughout their life span, with formation of each new organ involving the de novo formation of a stem cell niche driving organ growth. Major research questions involve which processes pattern the stem cell niche and meristimatic region of dividing cells emanating from it, and which processes prepattern the locations along the main root competent for the future formation of lateral roots. In our research we use multi-scale cell-based models incorporating gene expression, hormonal signalling as well as growth, division expansion and differentiation of cells to answer these questions. Using this approach we previously demonstrated a division of labor between auxin and the downstream PLETHORA transcription factors in determining meristem size and rates of division, elongation and expansion (Mahonen et al., Nature, 2014). We subsequently recently demonstrated that the auxin-PLETHORA-ARR network controls activation, outgrowth and stabilisation of the root meristem after germination (Salvi et al, Dev Cell, 2020). Additionally, we have shown how lateral root priming emerges from the synergy between plant root tip auxin transport and root growth dynamics (van den Berg et al, Dev Cell 2021). In a next step we demonstrated the importance of discerning auxin levels versus auxin signalling capacity, with the former driving the priming process yet the second essential for primed cells to remember and maintain their lateral root forming competence (Santos Teixeira et al, Development 2022).

In addition to focussing on patterning along the longitudinal axis of the root, we have recently also contributed to elucating radial root patterning. For this we collaborated with the Mahonen and Etchels groups to unravel the positioning of the cambium stem cell niche responsible for thickness growth (Eswaran et al, 2024 Science).


Plant development also differs from animal development in that it is highly plastic, leading to non-stereotypical, environmentally dependent plant architectures. As an example, plant roots show directional growth, called tropisms, towards gravity but also away from salt. Additionally, in response to heterogeneous nutrient supplies, plant root systems show a preferential proliferation of roots in nutrient rich patches, called preferential root foraging. Tropisms can still be effectively studied by cell-based models of a single root, enabling us to succesfully identify additional genes contributing to the auxin asymmetry underlying root salt avoidance (van den Berg et al, Development,2016;Korver et al., Plant Cell Env, 2020. However, to adress which processes give rise to an asymmetric growth of different parts of the root system in response to differences in their local nutrient conditions we need to expand to spatially more coarse-grainded FSP-type multi-scale models of overall root architecture. Using simplified models of this type we have already demonstrated that local, long-range and systemic nutrient signalling are likely insufficient to explain preferential nitrate foraging, and that the competition between roots for carbon resources further amplifies nutrient-difference induced asymmetries (Boer et al., Front Plant Sci,2020). To further enhance the realism and power of this overal root architecture modeling approach we recently developed our own biophysical model for water and carbon transport (van den Herik et al., Plant Cell Env, 2020) that can easily be integrated in this framework.

Cell fate decision making

During development cells have to decide whether to keep dividing and maintain an undifferentiated state, or rather differentiate and stop dividing. Additionally, upon differentiation choices between alternative cell fates have to be made. Importantly, in healthy non-cancer cells, the decision to differentiate is irreversible and terminal differentiation is mutually exclusive with an active division status. A key question is how the architecture and dynamics of the regulatory networks -genetic, epigenetic and posttranscriptional- controlling cell behavior give rise to these decisions in cell fate.

To adress these questions, we recently started a project in collaboration with the C.elegans groups of Sander van den Heuvel and Rik Korswagen, as well as with the labs of Alexander van Oudenaarden en Michiel Vermeulen. The overarching idea is to use single cell transcriptomics as well as epigenetic and protein data to reverse engineer the architecture and dynamic functioning of the network underlying mesoblast and neuron differentiation in C. elegans.

By combining omics based network inference and differential equation based modeling of gene expression dynamics, we aim to determine through sophisticated fitting and optimization procedures the architecture of the core regulatory networks involved.

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