Douglas Allan

The Allan laboratory uses a suite of molecular genetics, biochemistry and imaging approaches to study the modulation and maintenance of neuronal identity, with specific focus on defining the molecular mechanisms by which retrograde signals from synaptic targets control neuronal identity and the homeostasis of synaptic function. An increasing interest in using Drosophila melanogaster as a tool for understanding human disease has led to work in tauopathy and in human variant functionalization.

Drosophila melanogaster has long been a leading model organism for identifying and studying the biological mechanisms that underlie human heredity, development, health and disease. Understanding the development and function of neurons within a complex nervous system is a particularly daunting task that requires the use of sophisticated genetic tools. The unparalleled 100yrs of genetic analysis together with the rapid adoption of novel molecular genetic approaches means that, today, Drosophila offers the most sophisticated array of technologies with which to study neuronal development, maintenance and function in vivo.

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.

ΓÇïDisruption 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

ΓÇïNext-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 developing Drosophila assays to interpret the pathogenicity of gene variants for numerous human diseases.