Peptide Neurobiology Laboratory
Laboratory Head
A/Prof Andrew L Gundlach BSc (Hons) (Mon) Dip Ed (Mon) PhD (Melb)
Contact Details
Email: | |
Phone: | +61 (0)3 8344 7324 |
Fax: | +61 (0)3 9348 1707 |
Number of
Staff: 4
- Pei-Juan Shen BSc (Hons) (East China Normal) PhD (Mon) (on LSL)
- Qian Sang BMed (Beijing Medical) PhD (Melb)
- Sherie Ma BSc (Hons) (Mon) PhD (Melb)
- Craig Smith BBMSc (Hons) (Melb)
Students: 3
PhD
- Avantika Banerjee BBiomed Sci (Hons) (Melb)
- Philip Ryan MBBS, BMSc (Hons) (Melb)
Honours
- Nilushi Karunaratne BSc (Melb)
Research Interests
Neuropeptides are widely distributed throughout the body and they commonly co-exist with and complement actions of classic neurotransmitters. The functions of neuropeptides via their G-protein-coupled receptors range from neural or glial transmitter to hormone and growth factor. Much evidence indicates that neuropeptides are of particular importance when the nervous system is challenged by stress, injury or substance abuse. These features and the large number of neuropeptides and peptide receptors provide opportunities for the discovery of new drug targets for treatment of nervous-system disorders.
The peptides relaxin, relaxin-3 and insulin-like peptide-3 (INSL3) have various essential biological roles. Relaxin acts in peripheral tissues to regulate collagen turnover and stimulate growth, angiogenesis and vasodilatation. INSL3 is essential for germ cell maturation and may regulate fertility in men and women. Importantly, receptors for both these hormones are present in key circuits in the brain, but their biological importance is still to be discovered. Similarly, relaxin-3 is an abundant neuropeptide recently discovered in our laboratory, and it also has a range of potential roles in animal and human behaviours, including feeding, stress responses and learning and memory.
Current Projects
- Relaxin-3 and nucleus incertus regulation of septohippocampal theta rhythm and spatial memory - peptide- and viral-based studies
- Role of relaxin-3 systems in arousal/motivation, stress and circadian rhythms
- Cellular physiology of the nucleus incertus - a novel, ascending arousal system?
- Relaxin-3 signaling and complex behaviour – insights from peptide gene knockout and receptor transgenic mouse strains
- Relaxin hormone systems in brain – studies in a receptor-gene knockout reporter mouse
- Insulin-like peptide-3 systems in corticothalamic- basal ganglia- and limbic- circuits - effects on stereotypic and social behaviour.
These studies involve collaborations with scientists at Johnson & Johnson Pharmaceutical Research & Development LLC (USA), the Universities of Valencia, Navarra and Autonoma de Madrid (Spain), Jagiellonian University (Poland), The University of Sydney and The University of Melbourne.
PhD and Honours projects are available to study the anatomy, regulation and function of the relaxin family peptide-receptor systems. Students will undergo training in systems neuroscience, including techniques of molecular and cell biology, peptide/receptor neurochemistry, and animal behavioural testing. Students will also be able to interact with our international collaborators in the USA and Europe, with the opportunity to conduct some of their studies overseas.
Laboratory Techniques
- Neuroanatomy – biochemical and functional mapping of circuitry related to peptide pathways and associated behaviours
- Histochemistry/molecular biology - immunohistochemistry, in situ hybridization and in vitro autoradiography of peptides, receptors and other markers; real time-, RT-PCR peptide/receptor gene analysis
- Physiology/pharmacology - small animal surgery, whole animal telemetry recordings in vivo recordings and behavioural tests after peptide treatment
- Behavioural neuroscience - motor, cognitive and affective test battery studies of gene-deletion and transgenic mouse strains
Funding
- National Health and Medical Research Council (Australia)
- Johnson & Johnson Pharmaceutical Research & Development, LLC (USA)
- Pratt Foundation
- ANZ Trustees Medical Research & Technology (Victoria)
- Perpetual Trustees
- The Feilman, Eirene Lucas and GW Vowell Foundations
Publications and Articles
PubMed (uses “Gundlach AL” as unique author search)
Selected Recent Publications
Research Articles
Burazin TCD, Bathgate RAD, Macris M, Layfield S, Gundlach AL, Tregear GW. (2002) Restricted, but abundant, expression of the novel rat gene-3 (R3) relaxin in the dorsal tegmental region of brain. Journal of Neurochemistry 82: 1553-1557.
Shen P-J Larm JA, Gundlach AL. (2003) Expression and plasticity of galanin systems in cortical neurons, oligodendrocyte progenitors and proliferative zones in normal brain and after spreading depression. European Journal of Neuroscience 18: 1362-1376.
Jungnickel SR-F, Gundlach AL. (2005) [125I]-Galanin binding in brain of wildtype, and galanin- and GalR1- knockout mice: Strain and species differences in GalR1 density and distribution. Neuroscience 131: 407-421.
Ma S, Roozendaal B, Burazin TCD, Tregear GW, McGaugh JL, Gundlach AL. (2005) Relaxin in the basolateral amygdala impairs consolidation of fear memory. European Journal of Neuroscience 22: 2117-2122.
Fu P., Shen P-J, Zhao C-X, Scott DJ, Samuel CS, Wade JD, Tregear GW, Bathgate RAD, Gundlach AL. (2006) Leucine rich repeat-containing G-protein-coupled receptor 8 in mature glomeruli of developing and adult rat kidney and inhibition by INSL3 of glomerular cell proliferation. Journal of Endocrinology 189: 397-408.
Ma S, Shen P-J, Burazin TCD, Tregear GW, Gundlach AL. (2006) Comparative localization of LGR7 (RXFP1) mRNA and [33P]-relaxin binding sites in rat brain: Restricted somatic co-expression a clue to relaxin action? Neuroscience 141: 329-344.
Ma S, Bonaventure P, Ferraro T, Shen P-J, Burazin TCD, Bathgate RAD, Liu C, Tregear GW, Sutton SW, Gundlach AL. (2007) Relaxin-3 in GABA projection neurons of nucleus incertus suggests widespread influence on forebrain circuits via G-protein-coupled receptor-135 in the rat. Neuroscience 144: 165-190.
Gundlach AL, Ma S, Sang Q, Shen P-J, Piccenna L, Sedaghat K, Smith CM, Bathgate RAD, Lawrence AJ, Tregear GW, Wade JD, Finkelstein DI, Bonaventure P, Liu C, Lovenberg TW, Sutton SW (2009) Relaxin family peptides and receptors in mammalian brain – anatomical insights and diverse functional possibilities. Annals of New York Academy of Sciences 1160: 226-235.
Banerjee A, Shen P-J, Ma S, Bathgate RAD, Gundlach AL (2009) Swim stress excitation of nucleus incertus and rapid induction of relaxin-3 expression via CRF1 activation. Neuropharmacology (in press).
Ma S, Sang Q, Lanciego JL, Gundlach AL (2009) Localization of relaxin-3 in brain of Macaca fascicularis – Identification of a nucleus incertus in primate. Journal of Comparative Neurology (in press).
Ma S, Olucha-Bordonau FE, Hossain MA, Lin F, Kuei C, Liu C, Wade JD, Sutton SW, Nunez A, Gundlach AL (2009) Modulation of hippocampal theta oscillations and spatial memory by relaxin-3 neurons of the nucleus incertus in the rat. Learning and Memory (in press).
Wraith DC, Pope R, Butzkueven H, Holderd H, Vanderplank P, Lowrey P, Daye MJ, Gundlach AL, Kilpatrick TJ, Scolding N, Wynick D (2009). A role for galanin in human and experimental inflammatory demyelination. Proceedings of the National Academy of Sciences USA (in press).
Recent Reviews
Bathgate, RAD, Burazin, TCD, Samuel, CS, Gundlach, AL, Tregear, GW. (2003) Novel relaxin peptides and receptors. Trends in Endocrinology and Metabolism 14: 207-213.
Ma S, Gundlach AL. (2007) Relaxin-family peptide and receptor systems in brain. Insights from recent anatomical and functional studies. In: Relaxin and Related Peptides, Agoulnik AI (Ed), Landes Bioscience, Houston, TX, pp 1-19.
Lang, R, Gundlach, AL, Kofler B (2007) The galanin peptide family: Receptor pharmacology, pleiotropic biological actions, and implications in health and disease. Pharmacology and Therapeutics 115: 177-207.
Research
