SoMS, BABS and GSBE Cross-Faculty Seminar Series
Understanding the molecular mechanisms that regulate axonal regeneration is essential for the development of effective therapies for nerve injuries. Despite substantial knowledge being gained into how axonal re-growth is initiated, our understanding of the mechanisms needed to achieve target reconnection remains very poor. In several species, reconnection of severed axons can occur through a process of axonal fusion, whereby the proximal regrowing fragment recognises and re-establishes membrane and cytoplasmic continuity with its own separated distal fragment, preventing it from undergoing degeneration. This represents a highly efficient way to re-establish connection between an injured neuron and its target tissue. Using the nematode C. elegans as a model system, we have characterised the axonal fusion process at the molecular level.
We discovered that the recognition between the regrowing axon and its separated axonal fragment proceeds using the same conserved molecular elements previously shown to mediate the recognition of apoptotic cells by neighbouring phagocytes. Furthermore, we demonstrated that the re-establishment of membrane and cytoplasmic continuity between the two axonal fragments is achieved through the regulated expression and localisation within the damaged neuron of fusogens, molecules known to mediate developmentally regulated cell-cell fusion in most eukaryotes. These discoveries pave the way for the development of novel strategies for the treatment of nerve injury.
Bio:Associate Professor Massimo A. Hilliard received his PhD in Biological Chemistry and Molecular Biology in 2001 from the University of Naples, Italy, working under the supervision of Dr Paolo Bazzicalupo. He then undertook postdoctoral training with Prof William Schafer at the University of California San Diego, and with Prof Cori Bargmann at the University of California San Francisco and The Rockefeller University. In 2007, he was appointed as a Senior Research Fellow at the Queensland Brain Institute, The University of Queensland, where he has established his independent laboratory. He was subsequently awarded an ARC Future Fellowship, and in 2015 was promoted to Associate Professor and awarded an NHMRC Senior Research Fellowship.
During his career A/Prof Hilliard has focused on understanding the molecular mechanisms that regulate neuronal development, maintenance, and repair, using C. elegans as a model system. His current research goals are to understand: i) how the axon develops and maintains its structure over the lifetime of the organism, and ii) how the axon can be repaired when damage occurs. His laboratory has made a number of key discoveries in these research areas, including the axonal protective function of a conserved alpha tubulin acetyltransferase, the role of conserved apoptotic molecules in axonal clearance, and the identification of the molecular mechanisms that regulate axonal fusion, an axonal repair event in which the two separated fragments of an injured axon rejoin and reconstitute the original tract. His research has been funded by the NIH, NHMRC, and ARC, and his discoveries have been published in top tier journals, including Nature and Science.