BSc, DipSci (1st Class Hons.), MSc (1st Class Hons.), PhD, FRSNZ
We are interested in understanding the causes and developing treatments for human neurodegenerative disorders such as Alzheimer's disease, Stroke, Parkinson's disease, Motoneuron disease, Epilepsy, and Huntington's disease. My lab uses cell lines to dissect out the cellular and molecular cascades regulating processes such as nerve cell death, survival, and repair. These cell lines (alone and in co-culture) are also used to make in vitro models of neurodegenerative disorders and as cell-based screens for bio-active & biotoxic substances.
More recently, we have been developing methods to directly study cells grown from adult human brain tissue (biopsy and autopsy tissue donated to the Human Brain Bank for research into the causes and treatment of Neurodegenerative disorders). We have been investigating the biology and chemistry of microglia and astrocytes (cells which are pivotal in both neurodegeneration and repair) as well as adult human brain stem cells. By studying the basic biology of these adult human brain cells we are beginning to unravel their role in human neurodegenerative disorders. The work on the adult human brain stem cells is concerned with discovering the factors that control their survival, proliferation and differentiation into neurons and astrocytes. This knowledge is essential for developing new drug treatments to encourage the brain's own capacity for repair and regrowth.
Research is also directed at studying the molecular pathology of diseased adult human brain in collaboration with Professor Richard Faull. We are currently developing tissue microarray technology of adult human brain to greatly speed up this molecular pathology work.
In conjunction with the cell-based and human tissue-based work we have been developing high-content analysis and high-through-put screening technologies for cell-based assays as tools for drug screening, functional genomics and chemical genetics, and for studies of mechanisms of drug action on the brain. High Content Analysis is the combined use of high throughput microscopy and image analysis to quantify complex cellular information such as morphology, signal intensity and signal location in a cell or organelle within a cell. The platform that we have developed with funds from one of New Zealand’s Centres of Research Excellence, the Gravida: National Centre for Growth and Development, is based around the Discovery-1 microscope and the Metamorph image analysis system. Discovery 1 is an automated inverted fluorescence and brightfield microscope and Metamorph is a powerful high throughput automated image analysis tool. Discovery-1 is revolutionizing the study of the complex “orchestra” of signals that permeate between and within cells (Signal transduction research). We have established this platform for cell-based and human brain tissue microarray studies and as a platform for the Gravida: National Centre for Growth and Development.
Our goal is to apply these adult human brain cell culture and tissue microarray platforms and the associated high throughput technologies to drug discovery and testing for the development of treatments (astro- and neuro-protective agents and agents to enhance neurogenesis) for people suffering from neurodegenerative disorders.
Research Fellows
Dr Hannah Gibbons
Research Staff
Miranda Aalderink, Sheryl Feng, Deidre Jannsson, Claire Lill
PhD students (Main Supervisor)
Ursula Byrne, Natacha Coppitiers, Pritika Narayan, Thomas Park, Amy Smith
PhD students (Co-supervisor)
Melanie Cheung, Catherine Goodfellow, Natasha Grimsey.
Research Grants
The Lynette Sullivan Family Trust
The Coker Charitable Trust
Health Research Council Programme Grant
FRST grant
Centre of Excellence Grant (Gravida: National Centre for Growth and Development)
Marsden Fund
Selected publications
- Shinjyo et al. Complement-derived anaphylatoxin C3a regulates in vitro differentiation and migration of neural progenitor cells. Stem Cells 27, 2824-2832, 2009.
- Scotter E, Narayan P, Glass M, Dragunow M. High Throughput Quantification of Mutant Huntington Aggregates. Journal of Neuroscience Methods 171, 174-179, 2008.
- Byrne U, Bond J, Faull RLM, Dragunow M. High-throughput quantification of Alzheimer’s disease pathological markers in the post-mortem human brain. Journal of Neuroscience Methods 176, 298-309, 2009.
- Dragunow M. The adult human brain in preclinical drug development. Nature Reviews Drug Discovery 7, 659-666, 2008.
- Dragunow M. High content analysis in neuroscience. Nature Reviews Neuroscience 9(10), 779-88, 2008.
- Narayan P, Gibbons H, Mee E, Faull R, Dragunow M. High throughput quantification of cells with complex morphology in mixed cultures. Journal of Neuroscience Methods 164(2) 339-349, 2007.
- Gibbons H, Hughes S, Van Roon-Mom W, Greenwood J, Narayan P, Teoh H, Bergin P, Wood P, Mee E, Faull R, Dragunow, M. Cellular composition of human glial cultures from adult biopsy brain tissue. Journal of Neuroscience Methods 166, 89-98, 2007.
- Curtis MA, Kam M, Nannmark U, Anderson MF, Zetterstrom Axell M, Wikkelso C, Holtås S, van Roon-Mom W, Björk-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull R, Eriksson P. Human Neuroblasts Migrate to the Olfactory bulb via a Lateral Ventricular Extension. Science 315 (5816) 1243-1249, 2007.
- Dragunow M, Greenwood J, Cameron R, Narayan P, O’Carroll S, Pearson A, Gibbons H. Valproic acid induces caspase 3-mediated apoptosis in microglial cells. Neuroscience 140 (4) 1149-1156, 2006.
- Graham ES, Ball NB, Scotter EL, Narayan P, Dragunow M, Glass M. Induction of krox 24 by endogenous CB1 receptors in Neuro2a cells is mediated by the MEK-ERK MAPK pathway and is suppressed by the PI3K pathway. Journal of Biological Chemistry 281(39):29085-95, 2006.
- Dragunow M, Trzoss M, Brimble M, Cameron R, Beuzenberg V, Holland P and Mountford D. Investigations into the cellular actions of the shellfish toxin gymnodimine and analogues. Environmental Toxicology and Pharmacology 20, 305-312, 2005.
- Curtis MA, Penney EB, Van Roon W, Butterworth N, Pearson A, Dragunow M, Connor B, Faull RLM. Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain. Proceeding of the National Academy of Sciences (USA) 100 (15) 9023-9027, 2003.
- Zhang S, Liu J, Dragunow M, Cooper GJ. Fibrillogenic amylin evokes islet beta-cell apoptosis through linked activation of a caspase cascade and JNK1. Journal of Biological Chemistry 278 (52) 52810-52819, 2003.
- Greenwood J, Dragunow M. Muscarinic receptor mediated phosphorylation of CREB in human neuroblastoma cells. Journal of Neurochemistry 82, 389-397, 2002.
- Walton M and Dragunow M. Is CREB a key to neuronal survival? Trends in Neuroscience 23, 48-53, 2000.
|
