We are fascinated by the possibility of converting glial cells, a heterogeneous group of support cells found in the brain, into neurons in order to repair diseased brain circuits. To better understand this process we study the molecular trajectory of glial cells undergoing induced conversion into neurons.
Apart from a few exceptions, neurons mostly stop forming in humans and other mammals at around the time of birth. However, many brain diseases result in neuron death or dysfunction, with devastating consequences for brain circuit function. Thus, one possible way to restore brain function in these cases may involve regenerating these lost neurons
Our laboratory explores an innovative approach, namely the possibility of (re)generating neurons by locally converting glia, such as astrocytes or oligodendrocyte progenitors, into neurons, a process referred to as lineage reprogramming. We can induce lineage reprogramming by expressing transcription factors which activate genes associated with neuron development. To take this a step further, our research now aims to identify strategies that enable us to generate specific types of neurons with advantageous features. We hope that these glia-derived neurons may allow the remodelling of diseased brain circuits such as what we observe in epilepsy or neuropsychiatric disorders. To accomplish this we study the functional maturation and circuit integration of these newly induced neurons through live imaging and electrophysiology.
In order to further improve glia-to-neuron conversion we need a better understanding of the molecular trajectory glial cells undertake during the conversion process and to identify molecular roadblocks that impede successful neuron induction. At the Crick we study transcriptional and epigenetic changes experience by glia when reprogramming at the level of single cells. This will eventually allow us to close our gap in knowledge of what separates induced neurons from neurons that developed naturally in terms of molecular identity, morphology and function.