Most of our brain cells (neurons) are generated before we are born and can only be replaced to a very limited extent during our lifetime. Therefore, the brain must maintain its function throughout our lives without cell replacement. Professor Tomohisa Toda and his team are trying to understand how our brain cells are maintained and how they are affected by aging and age-related diseases. To do this, the scientists use state-of-the-art imaging and sequencing techniques.
To maintain cellular function, cells must express the correct combination of genes. This process is regulated by so-called epigenetic mechanisms, which regulate the gene activity of neurons without changing their DNA sequence. Toda’s team is investigating this epigenetic regulation at different levels – from small scales such as DNA modification to large scales such as nuclear rigidity and cell nucleus geometry.
Their research addresses two main questions. First, the scientists want to investigate the fundamental mechanisms underlying the long-term maintenance of cell type-specific epigenetic regulation. They also want to ascertain how the different levels of epigenetic regulation are linked. In particular they are interested in whether and how physical information from the cell nucleus can be used as epigenetic information. The second central topic of interest to the researchers is how aging impacts the identified mechanisms. It is known that epigenetic regulation is impaired during aging, but it is not clear how. Understanding the fundamental mechanisms underlying the longevity and survival of neurons is key to preventing and forming the basis for future treatment approaches for age-related neurological diseases such as Alzheimer's.