Markus Mittnenzweig wins ERC Starting Grant

How does a single cell know to become a heart, a muscle, or a neuron? The mystery of how life unfolds from a single cell into a complex, functioning organism has long fascinated biologists. For Dr. Markus Mittnenzweig, Group Leader of the Computational and developmental biology lab at the Max Delbrück Center, the question is more than just a matter of wonder – it is the focus of his career.

Now, with a prestigious European Research Council (ERC) Starting Grant of €1.5 million awarded over five years, Mittnenzweig will use a combination of technologies to understand the ballet of signals and spatial cues that nudge zebrafish embryos to develop specialized tissues and organs.  

“We can now measure and quantify many different layers of gene regulation and chart the transition from a mass of pluripotent cells – capable of becoming anything – into the explosion of diverse cell types that make up an embryo,” says Mittnenzweig.  

From the moment a fertilized egg begins to divide, the process of cellular differentiation transforms multi-purpose cells into specialists. Choreographed by shifting gene activity and other factors, once-pluripotent cells gradually commit to becoming muscle, blood, neurons, or myriad other tissue types. This transition is neither random nor linear – it is a tightly timed dialogue between the cell’s own genetic program and the cues it receives from its neighbors. Making deciphering this dynamic even more complex, the same signaling molecule can have multiple tasks – a single molecular cue can push one cell toward becoming a neuron while steering another toward blood, for example, depending on when it is expressed and the context.

Opening a new frontier

Markus Mittnenzweig

© Pablo Castagnola, Max Delbrück Center

Mittnenzweig will combine single-cell RNA sequencing with cell lineage tracing and spatial transcriptomics among other technologies to collect data from early stage zebrafish embryos as they develop over time. Using computational tools developed in his lab, he will analyze the data to create maps of which genes switch on or off, at what precise times and and of the communication among neighboring cells. He aims to then feed these maps into mathematical models to predict how a cell’s genetic and chemical signals influence its future behavior, and then run systematic experiments to test these predictions.

“We want to understand how these dynamics unfold in real time,” Mittnenzweig explains. By quantifying gene expression of cells in a spatial context, his models will reveal how networks of interacting cells orchestrate development. Moreover, he aims to reconstruct such cellular dynamics in 3D.

“Ten years ago, we couldn’t quantify the regulation of these processes in a spatial context at the single-cell level,” he says. “Now we can, and it will open an entirely new frontier.”

Text: Gunjan Sinha

Further information

Mittnenzweig Lab

Computational and developmental biology

• ERC Starting Grants
• ERC press release
• The modeler of cell development: Profile on Markus Mittnenzweig
• ERC grants at the Max Delbrück Center