Allan

Gene regulation in neurons

Complex nervous system function depends upon the generation of many different subtypes of neurons during development, and then lifelong modulation of synaptic function by trans-synaptic communication. We study the transcriptional mechanisms controlling gene expression programs that establish neuronal identity and modulate synaptic function in response to retrograde signals form the synapse. Ongoing projects explore how retrograde BMP signaling from the neuromuscular junction intersects with intrinsic transcription factors in motor neurons to direct synaptic growth and homeostasis. Disruption of transcription factors has been linked to congenital neurological disorders, and disruption of intercellular communication and trafficking of target-derived signals has been implicated in neurodegenerative disorders. Our studies provide a mechanistic understanding of how these factors control gene expression pertinent to neuronal function, advancing our understanding of the aetiology of neurological disorders.

Clinical interpretation of human gene variants in the Drosophila model 

Next-generation sequencing has made genetic variant discovery routine clinical practice. However, interpreting the functional consequence of identified variants is challenging. Drosophila offers advantages for scalable clinical variant interpretation. While different on a gross anatomical level, human and Drosophila organ systems and molecular pathways are conserved. Drosophila offers detailed information on genetic and protein interactions for thousands of genes, as well as a versatile and cost-effective suite of molecular genetic tools that makes gene variant analysis highly tractable. Ongoing projects are developingDrosophila assays to interpret the pathogenicity of gene variants for numerous human diseases