An ERC double for the MDC: Dr. Jan Philipp Junker and Dr. Gaetano Gargiulo have each been awarded an ERC Starting Grant worth €1.5 million. Junker will be studying cellular processes in the heart of the zebrafish, while Gargiulo will conduct research into glioblastoma, the most common form of brain tumor in humans.
How does a single fertilized egg cell produce the millions of precisely arranged cells that are present in vertebrates? This is the question being investigated by systems biologist Jan Philipp Junker. He is particularly interested in variable phenomena such as the position of the heart in zebrafish: in five percent of fish the heart is on the right instead of the left. These zebrafish are healthy and do not transmit the "error" to their offspring, which in 95 percent of cases have the heart on the left.
Junker will explore the mechanisms that cause such deviations in the SPACEVAR project (Quantitative analysis of variability and robustness in spatial pattern formation). "Until now this has not been possible, because no suitable methods were available. We want to understand how random processes in developmental biology occur and how they are corrected. The heart of the zebrafish is a good model for this," says Junker.
As part of the project, he and his team are developing the methods needed for the investigations. For example, the researchers use parentage relationships between single cells to work out how cell-lineage maps adapt when they are disturbed. This is done by labeling single cells of different types using gene editing method CRISPR/Cas9. A certain number of the labeled cells are then removed. "We are particularly interested in finding out how many cells we can remove without causing any abnormality and how the organism copes with these disturbances," says Junker.
The findings of the project, which is being funded for five years, could also contribute to a better understanding of how disorders - such as heart abnormalities - arise in human developmental biology.
Molecular geneticist Dr. Gaetano Gargiulo has set his research focus on glioblastoma multiforme (GBM), the most common, and incurable, primary brain tumor.
Notable for its lethality, GBM is highly heterogeneous and resistant to available treatments. The tumor's heterogeneity makes it difficult to decide which treatment will best fit any particular patient. Standard therapies either do not have any effect at all, or the patients quickly develop a resistance against them. Consequently, the median life expectancy of GBM patients is just 15 months.
In the project "Glioblastoma Subtype Avatar Models for Target Discovery and Biology" (iGBMavatars), Gargiulo and his team are targeting these two sticking points. The first step will be to create novel animal models for the glioblastoma that better resemble the human disease. Subsequently, this will allow the group to screen on a large scale for drug targets and molecular biomarkers.
"Our overall goal is to identify those molecular switches that can either increase or prevent the response of patients to standard therapy and to extend their life expectancy significantly. The most valuable information can only be obtained with the best possible disease models. With the aid of the powerful CRISPR/Cas9 technology, we can now execute both tasks with an unprecedented level of control," Gargiulo explains.
European Research Council (ERC) Starting Grants are awarded once a year; the ERC grant schemes are among the most important funding programs in Europe. With the grants to Jan Philipp Junker and Gaetano Gargiulo, the number of ERC grants awarded to MDC scientists since 2009 rises to 17.