Their labs are right next to each other, and now they have a reason to celebrate together: Dr. Jan Philipp Junker and Dr. Darío Lupiáñez have each been awarded a Consolidator Grant by the European Research Council (ERC). The two junior group leaders at the Berlin Institute for Medical Systems Biology (BIMSB) of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) are among the 61 grant winners from Germany. Out of the 2,652 researchers from across Europe who applied for the grants this year, 313 were chosen. These highly sought-after grants provide €2 million in funding over a period of five years. They give the best and brightest minds free rein to explore their ideas and advance their projects.
This is the second grant that Jan-Philipp Junker has received from the ERC. “It’s not just about the money, but about the visibility that comes with an ERC grant. It also allows you to think bigger and gives you more flexibility,” says the head of the Quantitative Developmental Biology Lab. Junker has been conducting research at the MDC since 2015. In the project “Heart States,” he wants to look at how the different cells of the zebrafish heart coordinate in a spatial and temporal way and thus enable the organ to heal itself. “The heart also serves as a model for our studies,” he says. “For example, how does a complex system respond to a perturbation?”
When he was a postdoctoral researcher, Dario Lupiáñez had already showed that the three-dimensional structure of the genome has consequences for the biology of an organism. “Back then, we were the first to demonstrate a connection,” says the head of the Epigenetics and Sex Development Lab. He has been conducting research at the MDC since 2017, and the project “3D Revolution” gives him another opportunity to do pioneering work. What interests him is how the way the DNA strand is packaged into the nucleus affects sex development in different animal species. “We want to shed light on the molecular mechanisms that allow species to adapt to their habitats and that drive their evolution,” he says. He will continue his project as a lab head at the Andalusian Center for Developmental Biology (CABD) in Seville starting in 2023.
Here are more details about the projects:
Zebrafish hearts heal themselves
When a human suffers a heart attack, permanent scar tissue is formed and the organ cannot fully recover. In zebrafish the situation is quite different. If the animal’s heart becomes injured, it simply heals itself. Medicine would like to copy this feat – at least some aspects of it. But there is still a long road ahead. Scientists first need to fundamentally understand the processes involved.
Junker’s Heart States project is investigating how the various cells in the heart manage to coordinate in such a spatiotemporal way as to bring about restored organ function. “For example, we have developed a sort of molecular time machine,” he says. This allows his team to track which genes the cells express at two different points in time. “These data show us which cell types in the zebrafish respond to the heart injury and temporarily enter an activated state, as well as the extent of the response.”
In a second step, Junker and his colleagues analyze what happens in each of these cells during this process: What mechanisms trigger the activation and what programs are switched on by the change in cell state? The third step concerns the coordination among the cells. “To orchestrate the healing process in the heart, the cells must communicate with each other,” Junker says. “And this requires us to know which cells were neighbors and whether receptors and ligands were spatially close.” Little by little, Junker’s team hopes to single out the key switches and verify their role in experiments, thereby creating the first comprehensive overview of how cell state transitions lead to the regeneration of a complex organ.
Focusing on a mature organ like the heart is also a gamble for him, Junker says. “My background is in developmental biology. So I’m all the more grateful to Daniela Panáková, who has been researching the zebrafish heart for a long time and who helped us a great deal with her knowledge and ideas during the conceptual phase.” The project is a perfect fit for the MDC, he says. All the expertise and resources needed to study the heart using a systems medicine approach can be found here, such as bioinformatics analyses, spatial transcriptomics and human cardiology. “Of course, it would be great to awaken the regenerative potential of the human heart,” Junker says. “But we will first have to perform experiments on mice: Perhaps mammalian hearts receive the right signals but can no longer respond to them?”
Gender issues have fascinated humans for 3,000 years
In the neighboring lab, Lupiáñez is also exploring a phenomenon that can work quite differently in the animal kingdom than in humans. “With our 3D Revolution project, we aim to answer a question that has fascinated humanity for almost 3,000 years: How is the sex of an individual determined?” Lupiáñez says. Ancient civilizations tried to explain this through mythology. “Now we use genetics.”
Evolution has come up with many different ways to determine sex – and the famous Y chromosome exists only in mammals. In birds, it is the females that carry the decisive chromosome. In amphibians such as frogs, the sex chromosomes are not well differentiated. And in more extreme cases, like turtles, temperature can determine whether an embryo will be male or female. “We will look at the 3D organization of genomes to understand how this rapidly evolving process happens at the molecular level,” Lupiáñez says.
Two meters of DNA are packed into each cell nucleus, which is about 200 times smaller than a pinhead. Yet still it is be able to deliver, on demand, all the information an organism needs for its development and survival. “The packaging is anything but random,” he says. “We have shown that alterations in the 3D organization of the genome can affect its regulation and lead to certain diseases. However, these changes can also contribute to the evolution of species and to a better adaptation to their habitats.”
He and his team will look at the exact time point when the sex is determined during the development of mammals, birds, amphibians and turtles. They will sift through the data and compare what the 3D gene regulatory landscapes have in common and what is susceptible to evolve. “This is unchartered territory; nobody has looked at this before,” Lupiáñez says. One reason is that the capability to read, interpret and modify genomes has constrained researchers in the past. “Now we have novel tools to link genomic variation to phenotypes,” he adds. “And the ERC grant will allow us to scale our efforts up. I am immensely grateful to my team who made great efforts in producing the necessary preliminary data.”
- – a portrait of Jan-Philipp Junker
Darío Lupiáñez in the lab. Photo:
Jan-Philipp Junker studies how the zebrafish heart regenerates. Photo:
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The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) is one of the world’s leading biomedical research institutions. Max Delbrück, a Berlin native, was a Nobel laureate and one of the founders of molecular biology. At the MDC’s locations in Berlin-Buch and Mitte, researchers from some 60 countries analyze the human system – investigating the biological foundations of life from its most elementary building blocks to systems-wide mechanisms. By understanding what regulates or disrupts the dynamic equilibrium in a cell, an organ, or the entire body, we can prevent diseases, diagnose them earlier, and stop their progression with tailored therapies. Patients should benefit as soon as possible from basic research discoveries. The MDC therefore supports spin-off creation and participates in collaborative networks. It works in close partnership with Charité – Universitätsmedizin Berlin in the jointly run Experimental and Clinical Research Center (ECRC), the Berlin Institute of Health (BIH) at Charité, and the German Center for Cardiovascular Research (DZHK). Founded in 1992, the MDC today employs 1,600 people and is funded 90 percent by the German federal government and 10 percent by the State of Berlin.