Research

Directional motion is a fundamental signature of living systems, arising across all scales ranging from the molecular to the tissue level. In fact, many key processes in development and disease, such as morphogenesis, immune response, and cancer invasion, rely on the coordinated directional movement of cells and tissues.

It is commonly assumed that this collective motion is steered by pre-patterned external chemical or mechanical cues, but it remains unclear how such robust, long-range guidance cues can be formed and maintained in a living organism.

My research seeks to fill this gap by exploring the principles of controlled vs. self-organized guidance across diverse biological systems. In particular, I aim to better understand (i) the development and maintenance of robust tissue structures, (ii) the mechanisms governing multicellular migration, and their connections to (iii) collective intracellular dynamics.

I employ a wide range of methods, including stochastic and PDE models, simulations, and link these theoretical insights closely with quantitative analysis of experimental data.

See Publications page for a detailed overview! Some selected projects are listed below:

Regulation of branching morphogenesis

A branching network guided by an external field in 3D.

Branched architectures are found in many organs such as lung, kidney, mammary & salivary glands, as well as in neurons and the vasculature. We look at how such branched morphologies are constructed robustly during development. In sensory neurons, we found some key theoretical signatures of external guidance cues controlling their final orientations, whereas local interactions, like self-avoidance of branches, mainly influence their space-filling features. 

We also study the development of the lymphatic system, which  is a transport network that controls immune response and tissue fluid circulation in the body.  We found that growing lymphatic networks combine complementary branching strategies to optimize tissue coverage: At the initial phase of development, they stochastically branch out and invade a territory. Late-stage morphogenesis, however, is controlled by targeted side-branching into sparse network regions to parsimoniously optimize space-filling.

Related publications:

Collective self-organized guidance of cells

Dendritic cells migrating in a uniform chemoattractant field. Imaging by Jonna Alanko from the Sixt group at IST Austria. 

Collective migration of cells can be driven by many different modes including chemical, mechanical, or topological/geometric cues. In many systems, cells can locally modify these cues to determine their directionality. We found that dendritic cells, the "messenger" cells of the immune system, can do this by using a single receptor, which both senses and consumes its ligand. Exploiting this self-generated chemotaxis mechanism, they steer their long-range migration.

We now explore theoretically the implications of this behavior for the coupled migration of mixed cell types, and experimentally by looking at the behavior of dendritic cells migrating together with T cells.

Related publications:

Mechanical interactions between molecular motors

Two antagonistic molecular motors engaging in a Tug-of-War.

Groups of molecular motors interact with each other mechanically through a common cargo, or by interlinking filaments. Such elastic interactions can lead to complex interference effects that influence their collective behavior such as force generation as a team. We found that this coordination heavily depends on their maximal force and their binding affinitiy to the filaments that they move on, leading to the counter-intuitive behavior that "weaker" motors collaborate better in collective force generation.

°Co-first author(s).
* Corresponding author(s).