Dr Massimo Hilliard - Molecular and Cellular Neurobiology
During his first postdoc at the University of California, San Diego, in the lab of Prof. William Schafer, using the Ca2+ indicator Cameleon he published the first direct visualisation of chemosensory activity in C. elegans neurons. In his second postdoctoral work, in the lab of Prof. Cori Bargmann at the University of California, San Francisco and at The Rockefeller University, he switched from neuronal function to neuronal development, focusing in particular on how neurons establish and orient their polarity with respect to extracellular cues.
In September 2007, he was appointed as a Senior Research Fellow at the Queensland Brain Institute, The University of Queensland, where he started his independent laboratory. The lab investigates the molecular mechanisms underlying maintenance of the axonal structure and regeneration following axonal injury, as well as axonal/dendrites guidance.
We use C. elegans as a genetic model system to study neuronal development. There are currently three lines of research in the lab, and PhD projects/Postdoctoral positions are available in each topic.
1. Axonal degeneration
How neurons can maintain their axonal structure and function over time is not well understood. Axonal degeneration is a critical and common feature of many peripheral neuropathies, neurodegenerative diseases and nerve injuries. The genetic factors and the cellular mechanisms that prevent axonal degeneration under normal conditions and that trigger it under pathological ones are still largely unknown. We aim to use C. elegans genetics to identify the molecules and the mechanisms that control these processes.
2. Axonal regeneration
How some axons can regenerate after nerve damage while others cannot is a crucial question in neurobiology, and the answers will be of great value for the medical handling of neurodegenerative diseases and of traumatic nerve injuries. Largely unknown are the molecules and the mechanisms underlying this important biological process. In C. elegans, a new laser-based technology allows single neuron axotomy in living animals, and axonal regeneration can now be visualised in real-time and tackled with a genetic approach. Our goal is to identify the genes and conditions that control this fascinating process.
3. Neuronal polarity and axonal guidance
Neurons are highly polarized cells with distinct domains such as axons and dendrites. The polarity of a developing neuron determines the precise exit point of its axon as well as the initial trajectory of axon outgrowth. Understanding how neurons establish and orient polarity with respect to extracellular cues is an important and challenging problem in neurobiology. We wish to understand how different secreted cues regulate the orientation of neuronal polarity and axonal/dendrite guidance in vivo.
- Assoc. Prof. Hang Lu, Georgia Institute of Technology, Atlanta
- Assoc. Prof. Yun Zhang, Harvard University, Cambridge
- Prof. Ding Xue, University of Colorado, Boulder
- Dr. Paolo Bazzicalupo and Dr. Elia Di Schiavi, Institute of Genetics and Biophysics, Naples, Italy
- Prof. Paul Ebert, The University of Queensland, Brisbane, Australia
- Kirszenblat, L., Neumann, B., Coakley, S., and Hilliard, M.A. A dominant mutation in MEC-7/β-tubulin affects axon development and regeneration in C. elegans neurons. Mol. Biol. Cell, 2013, 24: 285-296. doi:10.1091/mbc.E12-06-0441 (Cover image).
- Schlipalius, D.I., Valmas, N., Tuck, A.G., Jagadeesan, R., Ma, L., Kaur, R., Goldinger, A., Anderson, C., Kuang, J., Zuryn, S., Mau, Y.S., Cheng, Q., Collins, P.J., Nayak, M.K., Schirra, H.J., Hilliard, M.A.*, and Ebert, P.R.* A core metabolic enzyme mediates resistance to phosphine gas. Science, 2012, 338: 807 (2012). doi: 10.1126/science.1224951. *corresponding authors
- Cáceres IdC, Valmas N, Hilliard MA, Lu H. Laterally Orienting C. elegans Using Geometry at Microscale for High-Throughput Visual Screens in Neurodegeneration and Neuronal Development Studies.PLoS ONE, 2012, 7(4):e35037. doi:10.1371/journal.pone.0035037.
- Kirszenblat, L., Pattabiraman, D., and Hilliard, M.A. LIN-44/Wnt directs dendrite outgrowth through LIN-17/Frizzled in C. elegans neurons. PLoS Biology, 2011, 9(9): e1001157. doi:10.1371/journal.pbio.1001157.
- Neumann, B., Nguyen, K.C.Q., Hall, D.H., Ben-Yakar, A., and Hilliard, M.A. Axonal regeneration proceeds through specific axonal fusion in transected C. elegans neurons. Developmental Dynamics, 2011, 240: 1365-1372 (cover image).
- Hilliard, M.A. Axonal degeneration and regeneration: a mechanistic tug-of-war. Journal of Neurochemistry, 2009, 108: 23-32.
- Guo, S.X., Bourgeois, F., Chokshi, T., Durr, N.J., Hilliard, M.A., Chronis, N. and Ben-Yakar, A. Femtosecond laser nanoaxotomy lab-on-a-chip for in vivo nerve regeneration studies. Nature Methods, 2008, 5: 531-533.
- Hilliard, M.A. and Bargmann, C.I. Wnt signals and Frizzled activity orient anterior-posterior axon outgrowth in C. elegans. Developmental Cell, 2006, 10: 379-390.
- Pan, C.L., Howell, J.E., Clark, S.G., Hilliard, M.A., Cordes, S., Bargmann, C.I. and Garriga, G. Multiple Wnt homologs regulate anteriorly directed cell and growth cone migrations in Caenorhabditis elegans. Developmental Cell, 2006, 10: 367-377.
- Hilliard, M.A., Apicella, A.J., Kerr, R., Suzuki, H., Bazzicalupo, P. and Schafer, W.R. In vivo imaging of C. elegans ASH neurons: cellular response and adaptation to chemical repellents. EMBO J., 2005, 24: 63-72.
- Hilliard, M.A., Bergamasco, C., Arbucci, S., Plasterk, R.H.A. and Bazzicalupo, P. Worms taste bitter: ASH neurons, QUI-1, GPA-3 and ODR-3 mediate quinine avoidance in Caenorhabditis elegans. EMBO J., 2004, 23: 1101-1111.
- Hilliard, M.A., Bargmann, C.I. and Bazzicalupo, P. C. elegans responds to chemical repellents by integrating sensory inputs from the head and the tail. Current Biology, 2002, 12: 730-734.
- Salcini, A.E., Hilliard, M.A., Croce, A., Arbucci, S., Luzzi, P., Tacchetti, C., Daniell, L., De Camilli, P., Pelicci, P.G., Di Fiore, P.P. and Bazzicalupo, P. The Eps15 C. elegans homologue EHS-1 is implicated in synaptic vesicle recycling. Nature Cell Biology, 2001, 3: 755-760.