The focus of this research group is the hypothesis that nuclear remodeling is quintessential for the reprogramming of cell fate. Evidence from the Toda lab (TUD) shows that the nuclear pore protein nucleoporin 153 (Nup153) plays a key role in neural stem cell maintenance.
Using in vitro and in vivo models of glia-to-neuron conversion, which were developed by the Berninger lab (KCL), both partners explore the role of Nup153 and other nuclear structural proteins in reprogramming of glia into neurons. Here, the hypothesis that nuclear remodeling is quintessential for the reprogramming of cell fate is pursued. Towards this, the complementary expertise in super-resolution microscopy, epigenetic essays to probe for interactions between nuclear pore proteins and reprogramming factors, and functional gain- and loss-of-function studies of Nup153 in cultures of mouse primary astrocytes as well as the postnatal cortex in vivo plays a crucial role.
This study will lead to ground-breaking discoveries regarding the importance of nuclear architecture remodeling during cell fate conversion and pave the way for improved reprogramming strategies for brain repair. The observations may not be restricted to the central nervous system but are likely to be valid for other organs and tissues as well, such as pancreas and heart.