What is your main scientific aspiration?
I have always been fascinated by how the amazing diversity of cell types in the human body emerge from one single cell. This process is best illustrated by the cortex, the brain’s evolutionary youngest addition that is composed of an estimated 16 billion neurons connected by 153 million synapses.
The blueprint of the brain is what I want to unravel: how it emerges during development, its increasing complexity through evolution, and what happens if parts of the genetic program go astray. The latest technologies enable me to zoom into the heterogeneity of cells that make up a functional brain and to explore their specific genomes. I do not only strive to understand the intricacies of chromatin architecture – but also its impact on neuronal development and function.
Why did you choose to join the HPC?
I wanted to work in a research center that would enable me to focus on my scientific questions right from the start.
I joined the Helmholtz Pioneer Campus (HPC) in summer 2018, as an independent team leader, and without obligations to teach and only minimal administrative duties, the HPC allowed me to pursue my unique research questions on how the structure of the genome influences its function.
As one of the prestigious HPC team leader, I am benefiting from Munich’s first class scientific infrastructures and the Helmholtz Zentrum München’s worldwide networks.
I find the working atmosphere to be excellent and the administrative staff to be greatly supportive, as just experienced during the first recruitments to establish my own research team. Temporarily based at Helmholtz laboratories at the Ludwig-Maximilian-University’s Biomedical Center, I am priviledged to have an outstanding academic environment and unique potential for collaborations in both neuroscience and epigenetics.
How are you planning to answer your scientific questions?
As a developmental neurobiologist by training, I combine computational biology, single cell-omics and genome-editing tools in a truly innovative way. This empowers me to address key questions such as ‘how does cellular diversity emerge in the brain during development? – or during evolution?’. In particular, I focus on epigenetic mechanisms and 3D genome organization, which is an exciting new aspect of gene regulation and has emerged recently as intimately linked to transcription and cell fate. Changes in nuclear architecture and spatial positioning of gene loci can affect gene expression, and disruptions in topology can result in pathogenic phenotypes. To study chromatin organization globally, I use a variant of ‘chromosome conformation capture’ called Hi-C which allows me to capture chromatin contacts genome-wide. Having mapped 3D nuclear architecture at the highest resolution to date, I recently discovered that enhancer-promoter contacts are surprisingly dynamic during development and differentiation. I also showed that neural transcription factors are associated with cell-type specific 3D regulatory interactions and thus may have entirely unanticipated functions in remodeling the chromosomal architecture. Overall, my research contributed to unveil novel ways in the control of gene regulation – and consequently in the determination of cell fate. Such insights will open new avenues to better understand and possibly treat neurological disorders like autism and intellectual disability, which are frequently associated with mutations in chromatin-remodeling complexes.
Which are your interests beside research?
In my new role establishing and leading my own research program, I connect more actively my private interests with my professional challenges: to increase general awareness about my professional activities, I turned into an eager user of social media channels like Twitter or LinkedIn. To serve my curiosity and interests as keen reader, I started focusing on business-related non-fiction books: about people management or biographies of successful entrepreneurs. I really suggest young researchers to read the biography of Elon Musk and get inspired by him because it shows how important it is to have a strong vision and follow it through no matter how impossible it may appear to others. I’m fascinated by people who overcome boundaries, a spirit I want to foremost establish in my own lab, but also hope to instill into the ‘genome’ of our new and joint endeavor - the deployment of the Helmholtz Pioneer Campus.