The Austrian Science Fund (FWF) announced that it will fund two research projects at IMBA within its Principal Investigator Projects funding initiative. The funded projects, led by Jürgen Knoblich and Nicolas Rivron, further IMBA’s leading work using stem cell-based models to interrogate key biological questions without the need for animal models. 

Regenerating the brain with stem cells 

The human brain is arguably the most powerful organ found in nature, but it has an important weakness: its limited regenerative ability. Stem cell-based therapies have arisen in the last years as a promising approach to promote regeneration after brain injury caused by neurodegenerative diseases such as Parkinson’s disease and neurodevelopmental disorders such as epilepsy. However, developing these approaches relies on expensive, often non-translatable testing in animal models that opens ethical questions. 

To address this issue, the Knoblich lab’s project aims to establish cerebral organoids – stem cell-based models that recapitulate the development, structure and function of the human brain – as a model to test stem cell-based therapies. In recent years, the team has developed advanced cerebral organoid models mimicking the neuronal connections between different brain areas. Using patient-derived organoids, the team could replicate the pathological processes that cause Parkinson’s disease and epilepsy. The team now aims to test whether implanting healthy stem cells into these diseased models can help rescue the function of the affected neural circuits. By combining advanced electrophysiology, transcriptomics, and viral tracing, the team will track how implanted stem cells produce new neurons and how these integrate into existing neural circuits. Their results could inform new therapeutic approaches for patients with Parkinson’s disease and epilepsy. 

Studying human implantation in a dish 

Human embryos fail to implant at a very high rate, leading to 40 –to 70 percent of pregnancies being lost early on. This reproductive pitfall is due to the human embryo’s need to embed deeply into the endometrium through its placenta, a tissue that envelops the embryo and acts as the contact point with the endometrium. Using blastoids – a stem cell-based model of the human embryo – and endometrium models, the Rivron group aims to study the genetic and molecular mechanisms that control placenta connection to the endometrium. Their research will focus on how regulatory sequences have changed during human evolution as compared to other great apes to shape human-specific biology. The team will combine implantation assays with advanced sequencing and cross-species comparisons to identify what molecular differences drive our unique implantation strategy. The team’s findings could ultimately inform new strategies to improve fertility by reducing pregnancy loss. 

Manuel Matzinger participating in third project 

In addition, the project “3D Models & Single-Cell Tools for Placental Angiogenesis”, led by Sandra Haider at the Medical University of Vienna, also received FWF funding. Manuel Matzinger of the Proteomics Technology Hub is a co-beneficiary of this project, contributing his expertise in cutting-edge single-cell proteomics. Together, the project consortium will drive the development and analysis of advanced 3D placental models on a multiomic-level, helping to identify key signalling pathways and cell–cell interactions that shape early placental development. 

About FWF funding 

The Austrian Science Fund (FWF) is Austria's central funding organization for basic research. FWF Principal Investigator Projects grants support high-quality, innovative basic research across all disciplines. They provide funding for individual researchers or small teams to conduct independent research projects with international impact. Selection is based on scientific excellence and an international peer-review process.