17 May 2024 NWO M-grants for Ina Sonnen and Marvin Tanenbaum Back to news Ina Sonnen and Marvin Tanenbaum, group leaders at the Hubrecht Institute, have been awarded M-grants from NWO. The Sonnen group will use their grant to study the mechanism of how signalling oscillations regulate periodic somite formation in the vertebrate embryo. The Tanenbaum group will investigate the determinants of a successful viral infection and why some people become sicker than others when they are infected with the same virus. Ina Sonnen: Disassembling the morse code of our body All animals are composed of a multitude of cells that collaborate to form tissues and organs, enabling the body to function harmoniously. In these multicellular organisms, cells rely on communication mechanisms, such as signalling pathways, to control development and tissue maintenance. Two examples of pathways essential for such processes are Wnt and Notch signalling. Mutations in components of these pathways can lead to developmental defects or diseases like cancer. Therefore, understanding how signalling pathways operate has been a long-standing question in the field of multicellular biology. Read more Previous research has revealed that transmitting biological information does not only depend on whether a pathway is present or not, but also depends on how it changes over time, the signalling dynamics. A key model system to study signalling dynamics in multicellular systems is somitogenesis, a periodic segmentation process in which blocks of tissue known as somites form sequentially in the developing vertebrate embryo. These somites eventually give rise to important structures including the vertebrae, muscles, bones and skin. A network of signalling gradients and signalling oscillations, also known as the segmentation clock, determines the spacing and timing of somitogenesis. Previous research by the Sonnen group has shown that the relative timing between 2 oscillatory signals (Wnt and Notch) is critical for ensuring proper somitogenesis. This finding raises important questions about how the dynamics are controlled across the tissue and how it regulates somitogenesis. What makes the segmentation clock tick? The NWO M1 grant allows Sonnen to examine the idea that changes in the expression of components of signalling pathways regulate the signalling dynamics along the tissue, ultimately leading to the formation of segments. To test this hypothesis, the Sonnen group will use different state-of-the-art technologies to study both mouse embryos and gastruloids, aggregates of embryonic stem cells that recapitulate aspects of early embryonic development in a petri dish. Techniques like microfluidics, high-resolution real-time microscopy, transcriptomics, proteomics and genomics tools, will provide them with a mechanistic understanding of the vertebrate segmentation clock. First, they will identify regulators of the relative timing of signalling oscillations and study how the relative timing is decoded to allow vertebra formation. Then, they will confirm their findings in gastruloids, stem cell-based embryo-like structures of human development. This study will shed light on how biological information is encoded in signalling dynamics and in the relative timing between oscillatory signals. Ultimately, this may lead to a better understanding how defects in these processes can lead to developmental defects and diseases like cancer. Read less Marvin Tanenbaum: Visualizing viral infection one virus at a time Have you ever wondered why some people become a lot sicker than others when infected with the same virus? For example, some might suffer from a lot worse symptoms when infected with influenza than others who might barely notice the infection at all. This is related to the ability of the virus to cause a successful infection and will be what the Tanenbaum group will look into with their NWO grant. Read more Thousands of virus progeny or elimination Viruses are small infectious agents that have the ability to make us sick. Upon infection, some viruses will hijack our system in order to replicate itself so that they can infect more of our body’s cells. This is a very critical process for the virus as their ability to replicate themselves will determine how good they are at infecting our cells. Tanenbaum explains: ‘The outcome of infection can be very different; thousands of virus progeny can be produced, or the virus can be eliminated before replication occurs.’ This difference not only affects the number of cells that are infected but it can also affect the outcome of the disease. Currently, why the outcome of infections can be so variable is not well understood and therefore solving this mystery has been difficult. Tracking the infection from start to finish For the researchers to study the determinants of a successful infection, they need to track every step of the infection. Tanenbaum says: ‘Visualizing infection over time, especially in early infection is extremely difficult, due to an inability to detect the very small number of viral material present in individual cells.’ The researchers will use their M-invest grant to purchase an advanced, high-resolution, ultra-large field-of-view microscope which permits them to track infection in thousands of cells simultaneously and identify even one single viral genome in a living cell. The use of this microscope will enable the Tanenbaum group to study the viral infection cycle in great detail and to capture why infections progress differently in different cells. Read less About the NWO M-grant The NWO Open Competition Domain Science-M grants are intended for supporting non-programmed, curiosity-driven, fundamental research. These grants offer researchers the opportunity and freedom to start, and/or strengthen excellent, challenging and innovative lines of research, both monodisciplinary, multidisciplinary and interdisciplinary. Katharina Sonnen is group leader at the Hubrecht Institute Marvin Tanenbaum is group leader at the Hubrecht Institute, professor of Gene Expression Dynamics at TU Delft and Oncode Investigator.
