Dr. Alexandra Byrne is an Assistant Professor at the University of Massachusetts Medical School, where her lab is focused on understanding the molecular mechanisms that regulate an adult neuron’s ability to repair itself and regain function after injury or disease. Dr. Byrne received her PhD in Molecular and Medical Genetics from the University of Toronto, where she learned the power of using the genetically tractable C. elegans model to investigate conserved mechanisms of signal transduction and neurodevelopment. As a postdoctoral fellow in the Department of Genetics and the Program for Cellular Neuroscience, Neurodegeneration and Repair at Yale University, she continued to use C. elegans to search for conserved genes that determine an injured axon’s ability to regenerate. In so doing, she found that the loss of intrinsic regenerative ability in aging neurons is not merely a secondary consequence of a decrepit organism, but a genetically regulated process. Next, using a novel, genomic, cell type-specific expression assay, she discovered a number of previously unidentified intrinsic regulators of regeneration, one of which is poly-ADP ribosylation (PAR). Significantly, PAR’s role in regeneration is conserved in mammals and chemical inhibition of this pathway after injury restores regeneration to injured axons. Her lab is now eagerly expanding on these findings by investigating the pressing questions of how damaged axons avoid degeneration, how they initiate regeneration, how they are guided to their target cells and how they then form functional synapses. Her findings add significantly to our understanding of the intrinsic mechanisms that regulate an aging neuron’s ability to regenerate and reveal potential approaches to repair the injured and diseased nervous system.
Shared Mechanisms of Axon Regeneration and Degeneration
An injured or diseased axon has two choices: degenerate or regenerate. In the compromised central nervous system, regeneration is inhibited and degeneration is promoted, resulting in irreparable loss of neuronal function. How these two contrasting processes are coordinately regulated is not well understood. To address this question, we developed a novel in vivo injury model to screen for mutations that disrupt the balance between regeneration and degeneration of injured GABA axons. In this model, motor axons are severed into a proximal fragment that remains attached to the cell body and a distal fragment that is separated from the cell body. We identified a mutant strain with increased regeneration of the proximal segment, decreased degeneration of the distal segment, and improved functional recovery after injury. To coordinately inhibit axon regeneration of one fragment and promote degeneration of the other, the identified gene functions intrinsically in each to regulate divergent downstream genetic pathways on either side of the injury. Our findings present a potential opportunity to tilt the balance between degeneration and regeneration towards repair of the injured and diseased nervous system.