Chromatin remodelling during neuronal differentiation
When a neuron is born, it still has a long way to go before it is a full functional unit in the nervous system. Much has been learnt about the cellular changes that a neuron undergoes as it matures, however, much less is known about the chromatin remodelling process that are occurring during neuronal maturation. Our recent paper in eLife implicates a component of the condensin complex in this process.
Maintenance of a differentiated state
Related to chromatin remodelling during neuronal differentiation, we are investigating mechanisms that maintain neurons in a differentiated state. What are key factors and complexes that keep stem cell genes turned off in neurons? We are building on the recent discovery of a novel tumour suppressor, Lola, that prevents neurons dedifferentiating back into neural stem cells (Southall et al., 2014)
A powerful way to investigate the mechanisms that specify cell fate and cell properties is to profile gene expression patterns and transcriptional networks in a cell type-specific manner. TaDa allows cell type-specific profiling of protein-DNA interactions with ease. TaDa does not require specific antibodies, immunoprecipitation, fixation or cell isolation. See Southall et al. for more details (Aughey et al for review).
Specification of neuronal identity
The nervous system contains a diverse population of neurons with different properties - such as the neurotransmitters they utilise, their morphology, electrical properties and their preference for synaptic partners. How are these properties specified and maintained in vivo? We are using the cell type-specific profiling technique TaDa to address these questions by profiling transcription and transcription factor binding in specific neuronal populations. See our new paper in press and on BioRxiv
in vivo reprogramming of tissues
By combining research themes, we aim to establish the Drosophila nervous system as a platform for studying dedifferentiation of neurons into a pool of stem cells followed by directed differentiation into neurons of choice.