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Career Summary

Biography

Eleven peer-reviewed research publications from PhD studies

Awarded CJ Martin fellowship

Complete change in direction of research to acquire state-of-the-art techniques in USA

Returned to Australia and established single-cell genomics capability

Establishing new research program into the effects of aging on brain function.

Establishing collaborations with groups studying addiction and depression

Qualifications

  • Doctor of Philosophy, University of Queensland, 14/10/1995

Research

Research keywords

  • Aging and Brain Function
  • Animal Models
  • Cell Culture Models
  • Gene Expression
  • Immunocytochemistry
  • Mitochondrial genomics
  • Neuroanatomy
  • Single Cell Genomics
  • Viral Vectors

Research expertise

The main aim of my lab's research is to better understand the effects of ageing on nervous system function. It is well known that the world's population is ageing and soon there will be more people over the age of 65 than there are children. If we are to improve the quality of life of the aged, then we must first understand how ageing affects the body's various physiological systems. As the nervous system has an important role in most functions, its preservation with ageing is paramount. We are primarily using molecular approaches and focussing on ageing-related changes in the cell's two genomes - the nuclear and mitochondrial genomes. It is well-established that both genomes accumulate mutations with ageing, although it is not completely clear whether these mutations are more detrimental to cell function if they accumulate more so in one of the genomes as opposed to the other. It is also not known whether the mutation accumulations occur in a cell-specific manner. This is particularly important for the nervous system with its highly heterogeneous cell population. A number of nervous system functions appear more susceptible to the ageing process than others. For example, the special senses of hearing, vision and balance are particularly prone, although it remains to be determined whether the peripheral components of these systems (cochlea, retina, and vestibular apparatus, respectively) are more affected than their central nervous system connections and processes. Cognitive function and motor control are two more nervous system functions that are affected by the ageing process as can be readily observed in the aged population. We are characterising the genomic changes in specific populations of cells within these ageing-affected systems. For example, using state-of-the-art, laser based microdissection, we can collect midbrain dopamine neurons, which play an important role in motor control as can be appreciated from Parkinson's disease, at different ages and determine changes in mitochondrial DNA and the expression level of various genes. Similar approaches are being used for spinal cord motor neurons and inner ear vestibular hair cells. Knowing how ageing affects the nervous system is important, but we also need to be able to intervene if we are to improve the quality of life of aged individuals. Calorie restriction, whereby the daily calorie intake is reduced by 20-40% (but without malnutrition), is the only presently known intervention that retards the ageing process, at least in animal models. We are establishing CR to determine whether the ageing-related changes we see in the various cell populations of interest are modified by this intervention. If this is the case, we will then set out to determine how CR achieves this.

Research methods used in the lab include:

Animal models

Laser based microdissection

Immunocytochemistry

RNA and DNA techniques

Real-time and end-point PCR

Immunofluorescence microscopy

Cryosectioning

Fields of Research

CodeDescriptionPercentage
110399Clinical Sciences Not Elsewhere Classified50
060199Biochemistry And Cell Biology Not Elsewhere Classified25
170199Psychology Not Elsewhere Classified25

Awards

Research Award.

1995CJ Martin Fellowship
NHMRC (Australia)
The CJ Martin Fellowship is considered one of the most prestigious Australian postdoctoral fellowships

Teaching

Teaching keywords

  • Anatomy
  • Developmental Neurobiology
  • Ergonomics
  • Modern Techniques
  • Molecular Biology
  • Neurobiology
  • Physiology
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.

Click on a category title below to expand the list of citations for that specific category.

Journal article (32 outputs)

YearCitationAltmetricsLink
2014James MH, Campbell EJ, Walker FR, Smith DW, Hodgson DM, Dayas CV, Richardson HN, 'Exercise reverses the effects of early life stress on orexin cell reactivity in male but not female rats', Frontiers in Behavioral Neuroscience, 8 (2014)
2014James MH, Quinn RK, Ong LK, Levi EM, Charnley JL, Smith DW, et al., 'mTORC1 Inhibition in the Nucleus Accumbens 'Protects' Against the Expression of Drug Seeking and 'Relapse' and Is Associated with Reductions in GluA1 AMPAR and CAMKIIa Levels', Neuropsychopharmacology, (2014)
2014Thomas J, Garg ML, Smith DW, 'Dietary resveratrol supplementation normalizes gene expression in the hippocampus of streptozotocin-induced diabetic C57Bl/6 mice', JOURNAL OF NUTRITIONAL BIOCHEMISTRY, 25 313-318 (2014)
2014McIlroy DJ, Jarnicki AG, Au GG, Lott N, Smith DW, Hansbro PM, Balogh ZJ, 'Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery', Journal of Critical Care, - (2014)
2013Brown AL, Day TA, Dayas CV, Smith DW, 'Purity and Enrichment of Laser-Microdissected Midbrain Dopamine Neurons', BIOMED RESEARCH INTERNATIONAL, (2013) [C1]
2013Cahif A, Parkinson GM, Dayas CV, Smith DW, 'Characterisation of mitochondrial DNA deletions by long-PCR in central nervous system regions of young, middle- and old-aged rats.', Current Aging Science, 6 232-238 (2013) [C1]

Co-authors: Christopher Dayas

2013Thomas J, Garg ML, Smith DW, 'Altered expression of histone and synaptic plasticity associated genes in the hippocampus of streptozotocin-induced diabetic mice', Metabolic Brain Disease, 28 613-618 (2013) [C1]
2013Thomas J, Garg ML, Smith DW, 'Dietary supplementation with resveratrol and/or docosahexaenoic acid alters hippocampal gene expression in adult C57Bl/6 mice', Journal of Nutritional Biochemistry, 24 1735-1740 (2013) [C1]
2013Balogh ZJ, McIlroy DJ, Smith DW, Hansbro PM, 'The origin and the role of mitochondrial DNA in postinjury inflammation', Journal of Critical Care, (2013)
2012Barreto RDA, Walker FR, Dunkley PR, Day TA, Smith DW, 'Fluoxetine prevents development of an early stress-related molecular signature in the rat infralimbic medial prefrontal cortex. Implications for depression?', BMC Neuroscience, 13 1-12 (2012) [C1]
2012Dayas CV, Smith DW, Dunkley PR, 'An emerging role for the mammalian Target of Rapamycin (mTOR) in 'pathological' protein translation: Relevance to cocaine addiction', Frontiers in Pharmacology, 3 1-12 (2012) [C1]
2011Brown AL, Flynn JR, Smith DW, Dayas CV, 'Down-regulated striatal gene expression for synaptic plasticity-associated proteins in addiction and relapse vulnerable animals', International Journal of Neuropsychopharmacology, 14 1099-1110 (2011) [C1]

Co-authors: Christopher Dayas

2011James MH, Charnley JL, Flynn JR, Smith DW, Dayas CV, 'Propensity to 'relapse' following exposure to cocaine cues is associated with the recruitment of specific thalamic and epithalamic nuclei', Neuroscience, 199 235-242 (2011) [C1]

Co-authors: Christopher Dayas

2011James MH, Charnley JL, Levi EM, Jones E, Yeoh JW, Smith DW, Dayas CV, 'Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking', International Journal of Neuropsychopharmacology, 14 684-690 (2011) [C1]
2010James MH, Charnley JL, Jones E, Levi E, Yeoh JW, Flynn JR, et al., 'Cocaine- and amphetamine-regulated transcript (CART) signaling within the paraventricular thalamus modulates cocaine-seeking behaviour', Plos One, 5 e12980 (2010) [C1]
2009Brown AL, Smith DW, 'Improved RNA preservation for immunolabeling and laser microdissection', RNA: A Publication of the RNA Society, 15 2364-2374 (2009) [C1]
2009McInerny SC, Brown AL, Smith DW, 'Region-specific changes in mitochondrial D-loop in aged rat CNS', Mechanisms of Ageing and Development, 130 343-349 (2009) [C1]
2007Smith DW, Jinnah HA, 'Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice', Metabolic Brain Disease, 22 39-43 (2007) [C1]
2004Smith DW, Friedmann T, 'Discrepant effects of culture conditions on survival and function of dopaminergic neurons.', Neuroreport, 15 1025-1028 (2004) [C1]
2003Smith DW, Day TA, 'Catecholamine and oxytocin cells respond to hypovolaemia as well as hypotension', Neuroreport, 14 1493-1495 (2003) [C1]
2003Tokumine J, Kakinohana O, Cizkova D, Smith DW, Marsala M, 'Changes in spinal GDNF, BDNF and NT-3 expression after transient spinal cord ischemia in the rat.', Neuroscience Research, 74 552-561 (2003) [C1]
2002Visser JE, Smith DW, Fried T, Rothstein JD, Jinnah HA, 'Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease.', Brain Res Dev Brain Res, (2002) [C1]
2000Smith D, ' Characterization of the Dopamine Defect in Primary Cultures of Dopaminergic Neurons from Hypoxanthine Phosphoribosyltransferase Knockout Mice', Molecular Therapy, 1 486-491 (2000)
1999Buller KM, Smith DW, Day TA, 'Differential recruitment of hypothalamic neuroendocrine and ventrolateral medulla catecholamine cells by non-hypotensive and hypotensive hemorrhages', BRAIN RESEARCH, 834 42-54 (1999)
1999Buller KM, Smith DW, Day TA, 'NTS catecholamine cell recruitment by hemorrhage and hypoxia', NEUROREPORT, 10 3853-3856 (1999)
1995SMITH DW, SIBBALD J, KHANNA S, DAY TA, 'RAT VASOPRESSIN CELL RESPONSES TO SIMULATED HEMORRHAGE - STIMULUS-DEPENDENT ROLE FOR A1 NORADRENERGIC NEURONS', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 268 R1336-R1342 (1995)
1995SMITH DW, DAY TA, 'HYPOVOLEMIC AND OSMOTIC STIMULI INDUCE DISTINCT PATTERNS OF C-FOS EXPRESSION IN THE RAT SUBFORNICAL ORGAN', BRAIN RESEARCH, 698 232-236 (1995)
1995Smith DW, Buller KM, Day TA, 'Role of ventrolateral medulla catecholamine cells in hypothalamic neuroendocrine cell responses to systemic hypoxia', JOURNAL OF NEUROSCIENCE, 15 7979-7988 (1995)
1994KHANNA S, SIBBALD J, SMITH DW, DAY TA, 'INITIATION OF RAT VASOPRESSIN CELL RESPONSES TO SIMULATED HYPOTENSIVE HEMORRHAGE', AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 267 R1142-R1149 (1994)
1994SMITH DW, DAY TA, 'C-FOS EXPRESSION IN HYPOTHALAMIC NEUROSECRETORY AND BRAIN-STEM CATECHOLAMINE CELLS FOLLOWING NOXIOUS SOMATIC STIMULI', NEUROSCIENCE, 58 765-775 (1994)
1993SMITH DW, DAY TA, 'NEUROCHEMICAL IDENTIFICATION OF FOS-POSITIVE NEURONS USING 2-COLOR IMMUNOPEROXIDASE STAINING', JOURNAL OF NEUROSCIENCE METHODS, 47 73-83 (1993)
1992DAY TA, SIBBALD J, SMITH DW, 'A1-NEURONS AND EXCITATORY AMINO-ACID RECEPTORS IN RAT CAUDAL MEDULLA MEDIATE VAGAL EXCITATION OF SUPRAOPTIC VASOPRESSIN CELLS', BRAIN RESEARCH, 594 244-252 (1992)
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Conference (11 outputs)

YearCitationAltmetricsLink
2013Bigland M, Parkinson G, Brichta AM, Smith DW, 'Evidence for mitochondrial DNA deletions in vestibular hair cells of the aged rat', Proceedings of the Australian Neuroscience Society, Melbourne (2013) [E3]

Co-authors: Alan Brichta

2012Thomas J, Smith DW, Garg ML, 'Early molecular signature of neuro-protection in hippocampus of resveratrol diet fed C57BL/6 mice', Resveratrol 2012. 2nd International Conference of Resveratrol and Health, Leicester, UK (2012) [E3]

Co-authors: Manohar Garg

2012James MH, Charnley JL, Levi EM, Dunkley PR, Smith DW, Dickson PW, Dayas CV, 'A role for the mTOR pathway in the development of addiction', Abstracts. Australian Neuroscience Society 32nd Annual Meeting, Gold Coast, Queensland (2012) [E3]
2012Parkinson GM, Smith DW, 'Age-related increase in mitochondrial DNA copy number in midbrain dopamine neurons of the rat', Abstracts. Australian Neuroscience Society 32nd Annual Meeting, Gold Coast, Queensland (2012) [E3]
2012Dayas CV, Quinn RK, Goldie BJ, Brown AM, Levi EM, Smith DW, Cairns MJ, 'Association of miRNAs with addiction-relevant synaptic plasticity genes', Abstract Book. Biological Psychiatry Australia Scientific Meeting, Parkville, Vic (2012) [E3]

Co-authors: Christopher Dayas

2012Brown AL, Flynn JR, Dayas CV, Smith DW, 'Altered gene expression in cell signalling pathways of midbrain dopamine neurons from addiction and relapse vulnerable animals', Drug and Alcohol Review: Abstracts of the Australasian Professional Society on Alcohol and other Drugs Conference 2012, Melbourne, Vic (2012) [E3]

Co-authors: Christopher Dayas

2011Barreto RDA, Walker FR, Dunkley PR, Day TA, Smith DW, 'Alteration of neurotrophic factor pathway gene expression in the rat infralimbic medial prefrontal cortex by subchronic restraint stress is reversed by fluoxetine', Posters. Australian Neuroscience Society 31st Annual Meeting, Auckland, New Zealand (2011) [E3]
2011Thomas J, Smith DW, Garg ML, 'Dietary supplementation with resveratrol normalizes histone deacetylase (HDAC4) in the hippocampus of streptozotocin-induced diabetic mice', Australasian Medical Journal, Queenstown, NZ (2011) [E3]

Co-authors: Manohar Garg

2010Thomas J, Smith DW, Garg ML, 'Dietary supplementation with resveratrol reduces erythrocyte arachidonic and docosahexaenoic acids levels in diabetic mice', Proceedings of the Nutrition Society of Australia, Perth, WA (2010) [E3]

Co-authors: Manohar Garg

2007McInerny SC, Brown AL, Smith DW, 'Brain region-specific decrease in mitochondrial D-loop in aged rats (Poster)', 7th IBRO 2007 World Congress of Neuroscience Program, Melbourne (2007) [E3]
1995Day TA, Smith DW, Buller KM, 'Regulation of neurosecretory cell activity by A1 noradrenergic neurons', 1st Joint World Congress of Neurohypophysis and Vasopressin, Nasu Japan (1995)
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Grants and Funding

Summary

Number of grants14
Total funding$4,694,925

- Indicates that the researcher may be seeking students for this project.

Click on a grant title below to expand the full details for that specific grant.

2013 (1 grants)

Leica TP 1020 Automatic Tissue Processor for histology applications$35,000
Funding Body: NHMRC (National Health & Medical Research Council)

2012 (2 grants)

The effects of ageing on the peripheral vestibular system. Can ageing-related functional decline be reduced or prevented?$298,375
Funding Body: Garnett Passe and Rodney Williams Memorial Foundation

Project Team
Doctor Doug Smith
SchemeRole
Project GrantChief Investigator
Total AmountFunding StartFunding Finish
$298,37520122014
GNo:G1100935

2011 Emerging Research Leaders Program$15,000
Funding Body: University of Newcastle

Project Team
Doctor Doug Smith
SchemeRole
Emerging Research Leaders ProgramChief Investigator
Total AmountFunding StartFunding Finish
$15,00020122012
GNo:G1200307

2011 (1 grants)

Brain Mechanisms Conferring Psychostimulant Addiction$25,000
Funding Body: University of Newcastle

Project Team
Doctor Chris Dayas, Emeritus Professor Peter Dunkley, Doctor Doug Smith
SchemeRole
Near Miss GrantInvestigator
Total AmountFunding StartFunding Finish
$25,00020112011
GNo:G1001052

2010 (3 grants)

Laser microdissection microscopy system for cell and development biology$350,000
Funding Body: ARC (Australian Research Council)

Laser microdissection microscopy system for cell and development biology$215,000
Funding Body: University of Newcastle

ABI 7500 Real Time PCR System $34,000
Funding Body: NHMRC (National Health & Medical Research Council)

2008 (1 grants)

Dopamine mechanisms conferring resilience to depression: A new antidepressant target$538,500
Funding Body: NHMRC (National Health & Medical Research Council)

Project Team
Professor Trevor Day, Emeritus Professor Peter Dunkley, Professor David Pow, Doctor Doug Smith
SchemeRole
Project GrantInvestigator
Total AmountFunding StartFunding Finish
$538,50020082010
GNo:G0187604

2007 (2 grants)

Characterisation of the brain mechanisms linking vulnerability to stress and vulnerability to drug addiction$20,000
Funding Body: Hunter Medical Research Institute

Project Team
Professor Trevor Day, Doctor Chris Dayas, Doctor Doug Smith
SchemeRole
Project GrantInvestigator
Total AmountFunding StartFunding Finish
$20,00020072007
GNo:G0187255

Vulnerability to depression: the role of dopamine pathways$20,000
Funding Body: University of Newcastle

Project Team
Professor Trevor Day, Emeritus Professor Peter Dunkley, Doctor Doug Smith, Professor David Pow
SchemeRole
Near Miss GrantInvestigator
Total AmountFunding StartFunding Finish
$20,00020072007
GNo:G0187196

2004 (2 grants)

Characterisation of age-related gene expression changes in midbrain dopamine neurons$12,000
Funding Body: University of Newcastle

Project Team
Doctor Doug Smith
SchemeRole
New Staff GrantChief Investigator
Total AmountFunding StartFunding Finish
$12,00020042004
GNo:G0184998

Society for Neuroscience Annual Meeting, 23-27 October 2004$1,679
Funding Body: University of Newcastle

Project Team
Doctor Doug Smith
SchemeRole
Travel GrantChief Investigator
Total AmountFunding StartFunding Finish
$1,67920042004
GNo:G0184814

2003 (1 grants)

Genetic aberrations in HPRT deficiency$2,489,371
Funding Body: National Institute of Neurological Disorders (NIH)

SchemeRole
ProjectInvestigator
Total AmountFunding StartFunding Finish
$2,489,37120032007
GNo:22583579

2001 (1 grants)

Array screening for Lesch-Nyhan disese$641,000
Funding Body: NICH (NIH)

SchemeRole
R21Investigator
Total AmountFunding StartFunding Finish
$641,00020012003
GNo:22583591
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Research Supervision

Number of current supervisions4
Total current UoN PhD EFTSL1.9

For supervisions undertaken at an institution other that the University of Newcastle, the institution name is listed below the program name.

Current Supervision

CommencedProposed
Completion
ProgramSupervisor TypeResearch Title
20132017PhD (Medical Genetics)Co-SupervisorNucleotide Excision Repair of UVA-Induced DNA Damage: Regulation in Sunlight-Induced Melanoma
20122016PhD (Anatomy)Principal SupervisorAgeing of the Inner Ear Balance System
20112015PhD (Medical Biochemistry)Principal SupervisorAgeing of the Somatic Motor Nervous System: A Role for Mitochondrial and Nuclear Genome Changes
20072010PHD Medical Science
University of Newcastle
Principal SupervisorRole of dopamine in depression

Past Supervision

YearProgramSupervisor TypeResearch Title
2014PhD (Anatomy)Co-SupervisorThe Role of Cocaine- and Amphetamine-Regulated Transcript (CART) and Orexin in Drug-Seeking and Addiction-Related Behaviours
2013PhD (Medical Biochemistry)Co-SupervisorEffects of Anti-Inflammatory Bioactives on Diabetes-Induced Changes in Cognition-Related Gene Expression in the Hippocampus
2012PhD (Anatomy)Principal SupervisorMolecular Correlates of Dopamine Signalling in Addiction Vulnerability
2012PhD (Anatomy)Principal SupervisorDopaminergic Pathway Imbalance in the Neurobiology of Depression
2007Honours Medical Science
University of Newcastle
Principal SupervisorRole of mitochondrial D-loop in aging brain
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Dr Douglas (Doug) Smith

Work Phone(02) 4921 7108
Fax(02) 4921 8667
Email
PositionSenior Lecturer
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine
The University of Newcastle, Australia
Focus AreaAnatomy
Office
MS306B,
Medical Sciences,
Callaghan
University Drive
Callaghan NSW 2308
Australia
URL:www.newcastle.edu.au/profile/douglas-smith