Associate Professor Doug Smith
Associate Professor
School of Biomedical Sciences and Pharmacy (Anatomy)
- Email:douglas.smith@newcastle.edu.au
- Phone:0468473659
The age of reason
Dr Doug Smith is investigating the impacts of ageing on the nervous system, with the aim of identifying interventions that will extend healthspan.
Lifespan encapsulates the number of years you are alive, whereas healthspan refers to the number of years you maintain mental and physical health, without serious disease, during your lifespan.
Dr Doug Smith wants you to live better for longer. That doesn't necessarily mean living for longer, although that may be a benefit of good health. He isn't interested in finding the elixir of youth, just the key to maximum healthspan.
"Some people want to live forever, I have no interest in extending lifespan, I want to extend healthspan, it's a very different thing," he explains.
With life expectancy increasing and family sizes decreasing, our national population is ageing fast, prompting urgency in research in this field.
"In about 20 years from now, there are going to be more people living in Australia who are over the age of 65 then under the age of 15," Doug asserts.
"If more people reach their latter years still in pretty good shape, physically and mentally, then presumably we can lessen the health care cost burden."
"And more importantly, those people will have a better quality of life."
NERVOUS SYSTEMS
With a background in neurobiology, Doug is focusing his study on the impacts of ageing on the nervous system.
The central nervous system (CNS) includes the brain and spinal cord, whilst the peripheral nervous system (PNS) comprises all the body's nerve pathways outside of the CNS. Both the CNS and PNS are affected by ageing.
For example, declining senses, slowing of messages controlling movements, a loss of clarity in cognitive processes and failing memory are all nervous system specific changes that have been attributed to ageing.
Using an animal model to study the ageing brain, spinal cord and vestibular (balance) system, Doug and his collaborators hope to further understand these changes on a cellular and molecular level.
Together with his team, Doug uses modern genomics approaches, such as next generation sequencing, to obtain a global picture of age-related gene expression changes to inform their directions in the lab.
"There is much more that we don't know than we do know, so doing a discovery driven approach first, that can then can direct us, is very powerful," he says.
Doug and his team then use more traditional hypothesis driven approaches when looking to confirm or refute possible truths suggested by the broader genomics data.
MICRODISSECTION
Utilising laser-capture microdissection (LCMD) technology, the team are able to identify and extract specific cell types from the highly complex nervous system for study.
For example, LCMD extraction allows the team to investigate the effects of ageing on dopamine neurons, the degeneration of which causes Parkinson's disease. They also investigate the breakdown of the blood brain barrier, which is seen in vascular dementia.
Another study saw the team comparing levels of mitochondrial DNA mutation in young and old tissue. Mitochondria are the power generators of a cell and they have their own very small genome. Age-related mutations in this genome are thought to compromise the ability of mitochondria to generate energy for the myriad of cell activities needed for proper nervous system function.
"Based on our genomics findings we are now doing a lipidomics investigation," Doug explains.
"The CNS is chock full of different types of lipids, and we know they change with ageing, so we are trying to understand those changes in greater detail."
"Once we align these various approaches, it will give us a really good indication of where to head in terms of our more focused or directed studies."
THE NEXT GENERATION SEQUENCERS
Doug credits PhD and undergrad students with undertaking the bulk of the laborious lab work.
"We are always looking for more students who are passionate about biology and who would like to work with us," Doug says and adds, laughing, "Bring your own money!"
A senior lecturer in the School of Biomedical Sciences and Pharmacy, Doug admits that although teaching drains research time and energy, it actually enhances his outcomes.
"I actually believe that teaching is good for your research because when you teach you have to stand back and take a bigger picture view of things," he says.
"And when you do that, sometimes it gives you a different perspective for your research."
Doug was a post-doctoral scientist when a fascination with the biological phenomenon of ageing drew him to this field of study.
"I have always been curious, I have always wanted to know how things work," he conveys.
"Age related degeneration just doesn't make much sense. A lot of energy and effort goes into creating a sexually mature organism. So, why not then just maintain it? I find it very interesting."
AGEING GRACEFULLY
Although studies across species and domains show that ageing has a major impact on both the animal and human body, some individuals seem somewhat resilient to the effects of ageing.
"Everybody has a grandma or elderly uncle that still seems to be running around like a sprightly 30 or 40 year old, both mentally and physically they are doing really well," Doug acknowledges.
"We are trying to determine what it is about these individuals that allows them to have such a good healthspan."
"A potentially disappointing outcome of our work would be that we find out what the cause or causes of ageing are, but we can't find an intervention."
"However, there are many examples of people ageing well, and if you look at what they do, they are all pretty active, not just physically but mentally as well."
FREEDOM OF CHOICE
Due to the mounting evidence, Doug suggests it is more realistic to earn a longer healthspan, than win one in the unexplained resilience to ageing jackpot.
He refers to several existing intervention studies that show vastly different outcomes for participants relative to different diets and levels of exercise.
But don't wait too long. Evidence emerging from Doug's lab suggests the ageing process begins much earlier than we would like to believe.
"Preliminary data is certainly indicating that if you are going to live well, you can't wait until you are 75 and then decide to make healthier choices."
In the end, the solution to retarding the ageing process may simply involve choices around modifying behaviour.
"Once we characterise some of the processes of normal ageing, we can then go and see if a high fat, high sugar, Omega 3, or resveratrol diet, and/or exercise, are going to change the ageing process at the molecular, cellular, organ and whole body levels," Doug explains.
"The next step would be to design interventions that can be applied to human populations. Humans won't like some of the dietary restrictions, or the exercise. The red wine they might go for," he smiles.
"People will always have free will. We are just trying to figure out ways that are acceptable to the majority to help them to age well and stay active for longer."
The age of reason
Dr Doug Smith is investigating the impacts of ageing on the nervous system, with the aim of identifying interventions that will extend healthspan.
Career Summary
Biography
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 focusing 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
Qualifications
- Doctor of Philosophy, University of Queensland
Keywords
- Aging and Brain Function
- Anatomy
- Animal Models
- Cell Culture Models
- Developmental Neurobiology
- Ergonomics
- Gene Expression
- Immunocytochemistry
- Mitochondrial genomics
- Modern Techniques
- Molecular Biology
- Neuroanatomy
- Neurobiology
- Physiology
- Single Cell Genomics
- Viral Vectors
Fields of Research
Code | Description | Percentage |
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320903 | Central nervous system | 30 |
320905 | Neurology and neuromuscular diseases | 20 |
320902 | Cellular nervous system | 50 |
Professional Experience
UON Appointment
Title | Organisation / Department |
---|---|
Associate Professor | University of Newcastle School of Biomedical Sciences and Pharmacy Australia |
Academic appointment
Dates | Title | Organisation / Department |
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1/3/2005 - 21/6/2015 | Academic | University of Newcastle School of Biomedical Sciences and Pharmacy Australia |
1/7/1997 - 1/4/2004 | Research Scientist | University of California, San Diego Department of Pediatrics, School of Medicine UCSD United States |
Awards
Research Award
Year | Award |
---|---|
1995 |
CJ Martin Fellowship Unknown |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Journal article (56 outputs)
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2023 |
Poppi LA, Bigland MJ, Cresswell ET, Tabatabaee H, Lorincz D, Drury HR, et al., 'Molecular and Functional Changes to Postsynaptic Cholinergic Signaling in the Vestibular Sensory Organs of Aging C57BL/6 Mice.', J Gerontol A Biol Sci Med Sci, 78 920-929 (2023) [C1]
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2023 |
Lorincz D, Drury HR, Smith DW, Lim R, Brichta AM, 'Aged mice are less susceptible to motion sickness and show decreased efferent vestibular activity compared to young adults.', Brain and behavior, 13 e3064 (2023) [C1]
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2022 |
Gradwell MA, Smith KM, Dayas CV, Smith DW, Hughes DI, Callister RJ, Graham BA, 'Altered Intrinsic Properties and Inhibitory Connectivity in Aged Parvalbumin-Expressing Dorsal Horn Neurons', FRONTIERS IN NEURAL CIRCUITS, 16 (2022) [C1]
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2020 |
Madden JF, Davis OC, Boyle KA, Iredale JA, Browne TJ, Callister RJ, et al., 'Functional and Molecular Analysis of Proprioceptive Sensory Neuron Excitability in Mice', Frontiers in Molecular Neuroscience, 13 1-13 (2020) [C1]
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2020 |
Mayhew JA, Cummins MJ, Cresswell ET, Callister RJ, Smith DW, Graham BA, 'Age-related gene expression changes in lumbar spinal cord: Implications for neuropathic pain', Molecular Pain, 16 (2020) [C1] Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or ... [more] Clinically, pain has an uneven incidence throughout lifespan and impacts more on the elderly. In contrast, preclinical models of pathological pain have typically used juvenile or young adult animals to highlight the involvement of glial populations, proinflammatory cytokines, and chemokines in the onset and maintenance of pathological signalling in the spinal dorsal horn. The potential impact of this mismatch is also complicated by the growing appreciation that the aged central nervous system exists in a state of chronic inflammation because of enhanced proinflammatory cytokine/chemokine signalling and glial activation. To address this issue, we investigated the impact of aging on the expression of genes that have been associated with neuropathic pain, glial signalling, neurotransmission and neuroinflammation. We used qRT-PCR to quantify gene expression and focussed on the dorsal horn of the spinal cord as this is an important perturbation site in neuropathic pain. To control for global vs region-specific age-related changes in gene expression, the ventral half of the spinal cord was examined. Our results show that expression of proinflammatory chemokines, pattern recognition receptors, and neurotransmitter system components was significantly altered in aged (24¿32 months) versus young mice (2¿4 months). Notably, the magnitude and direction of these changes were spinal-cord region dependent. For example, expression of the chemokine, Cxcl13, increased 119-fold in dorsal spinal cord, but only 2-fold in the ventral spinal cord of old versus young mice. Therefore, we propose the dorsal spinal cord of old animals is subject to region-specific alterations that prime circuits for the development of pathological pain, potentially in the absence of the peripheral triggers normally associated with these conditions.
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2019 |
Duchatel RJ, Harms LR, Meehan CL, Michie PT, Bigland MJ, Smith DW, et al., 'Reduced cortical somatostatin gene expression in a rat model of maternal immune activation', PSYCHIATRY RESEARCH, 282 (2019) [C1]
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2019 |
Mayhew JA, Callister RJ, Walker FR, Smith DW, Graham BA, 'Aging alters signaling properties in the mouse spinal dorsal horn', MOLECULAR PAIN, 15 (2019) [C1]
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2018 |
McIlroy DJ, Minahan K, Keely S, Lott N, Hansbro P, Smith DW, Balogh ZJ, 'Reduced deoxyribonuclease enzyme activity in response to high postinjury mitochondrial DNA concentration provides a therapeutic target for Systemic Inflammatory Response Syndrome', JOURNAL OF TRAUMA AND ACUTE CARE SURGERY, 85 354-358 (2018) [C1]
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2018 |
Quinn RK, James MH, Hawkins GE, Brown AL, Heathcote A, Smith DW, et al., 'Temporally specific miRNA expression patterns in the dorsal and ventral striatum of addiction-prone rats', Addiction Biology, 23 631-642 (2018) [C1] MicroRNAs (miRNAs) within the ventral and dorsal striatum have been shown to regulate addiction-relevant behaviours. However, it is unclear how cocaine experience alone can alter ... [more] MicroRNAs (miRNAs) within the ventral and dorsal striatum have been shown to regulate addiction-relevant behaviours. However, it is unclear how cocaine experience alone can alter the expression of addiction-relevant miRNAs within striatal subregions. Further, it is not known whether differential expression of miRNAs in the striatum contributes to individual differences in addiction vulnerability. We first examined the effect of cocaine self-administration on the expression of miR-101b, miR-137, miR-212 and miR-132 in nucleus accumbens core and nucleus accumbens shell (NAcSh), as well as dorsomedial striatum and dorsolateral striatum (DLS). We then examined the expression of these same miRNAs in striatal subregions of animals identified as being ¿addiction-prone¿, either immediately following self-administration training or following extinction and relapse testing. Cocaine self-administration was associated with changes in miRNA expression in a regionally discrete manner within the striatum, with the most marked changes occurring in the nucleus accumbens core. When we examined the miRNA profile of addiction-prone rats following self-administration, we observed increased levels of miR-212 in the dorsomedial striatum. After extinction and relapse testing, addiction-prone rats showed significant increases in the expression of miR-101b, miR-137, miR-212 and miR-132 in NAcSh, and miR-137 in the DLS. This study identifies temporally specific changes in miRNA expression consistent with the engagement of distinct striatal subregions across the course of the addiction cycle. Increased dysregulation of miRNA expression in NAcSh and DLS at late stages of the addiction cycle may underlie habitual drug seeking, and may therefore aid in the identification of targets designed to treat addiction.
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2018 |
Robson AL, Dastoor PC, Flynn J, Palmer W, Martin A, Smith DW, et al., 'Advantages and limitations of current imaging techniques for characterizing liposome morphology', Frontiers in Pharmacology, 9 (2018) [C1]
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2018 |
Bigland MJ, Brichta AM, Smith DW, 'Effects of ageing on the mitochondrial genome in rat vestibular organs', Current Aging Science, 11 108-117 (2018) [C1] Background: Deterioration in vestibular function occurs with ageing and is linked to age-related falls. Sensory hair cells located in the inner ear vestibular labyrinth are critic... [more] Background: Deterioration in vestibular function occurs with ageing and is linked to age-related falls. Sensory hair cells located in the inner ear vestibular labyrinth are critical to vestibular function. Vestibular hair cells rely predominantly on oxidative phosphorylation (OXPHOS) for energy production and contain numerous mitochondria. Mitochondrial DNA (mtDNA) mutations and perturbed energy production are associated with the ageing process. Objective: We investigated the effects of ageing on mtDNA in vestibular hair and support cells, and vestibular organ gene expression, to better understand mechanisms of age-related vestibular deficits. Methods: Vestibular hair and supporting cell layers were microdissected from young and old rats, and mtDNA was quantified by qPCR. Additionally, vestibular organ gene expression was analysed by microarray and gene set enrichment analyses. Results: In contrast to most other studies, we found no evidence of age-related mtDNA deletion mutations. However, we found an increase in abundance of major arc genes near the mtDNA control region. There was also a marked age-related reduction in mtDNA copy number in both cell types. Vestibular organ gene expression, gene set enrichment analysis showed the OXPHOS pathway was down regulated in old animals. Conclusion: Given the importance of mtDNA to mitochondrial OXPHOS and hair cell function, our findings suggest the vestibular organs are potentially on the brink of an energy crisis in old animals.
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2018 |
Duchatel RJ, Meehan CL, Harms LR, Michie PT, Bigland MJ, Smith DW, et al., 'Late gestation immune activation increases IBA1-positive immunoreactivity levels in the corpus callosum of adult rat offspring', Psychiatry Research, 266 175-185 (2018) [C1] Animal models of maternal immune activation study the effects of infection, an environmental risk factor for schizophrenia, on brain development. Microglia activation and cytokine... [more] Animal models of maternal immune activation study the effects of infection, an environmental risk factor for schizophrenia, on brain development. Microglia activation and cytokine upregulation may have key roles in schizophrenia neuropathology. We hypothesised that maternal immune activation induces changes in microglia and cytokines in the brains of the adult offspring. Maternal immune activation was induced by injecting polyriboinosinic:polyribocytidylic acid into pregnant rats on gestational day (GD) 10 or GD19, with brain tissue collected from the offspring at adulthood. We observed no change in Iba1, Gfap, IL1-ß and TNF-a mRNA levels in the cingulate cortex (CC) in adult offspring exposed to maternal immune activation. Prenatal exposure to immune activation had a significant main effect on microglial IBA1-positive immunoreactive material (IBA1+IRM) in the corpus callosum; post-hoc analyses identified a significant increase in GD19 offspring, but not GD10. No change in was observed in the CC. In contrast, maternal immune activation had a significant main effect on GFAP+IRM in the CC at GD19 (not GD10); post-hoc analyses only identified a strong trend towards increased GFAP+IRM in the GD19 offspring, with no white matter changes. This suggests late gestation maternal immune activation causes subtle alterations to microglia and astrocytes in the adult offspring.
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2018 |
Arms L, Smith DW, Flynn J, Palmer W, Martin A, Woldu A, Hua S, 'Advantages and limitations of current techniques for analyzing the biodistribution of nanoparticles', Frontiers in Pharmacology, 9 1-17 (2018) [C1]
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2017 |
Khan SI, Hübner PP, Brichta AM, Smith DW, Migliaccio AA, 'Aging reduces the high-frequency and short-term adaptation of the vestibulo-ocular reflex in mice', Neurobiology of Aging, 51 122-131 (2017) [C1] Prevailing evidence indicates a relatively late life decline in human vestibulo-ocular reflex (VOR) function. Although mice are commonly used in mechanistic studies of vestibular ... [more] Prevailing evidence indicates a relatively late life decline in human vestibulo-ocular reflex (VOR) function. Although mice are commonly used in mechanistic studies of vestibular function, it remains unclear whether aging produces a corresponding decline in VOR function in mice. We sought to determine how the baseline VOR and its short-term adaptation were affected by aging. We tested 8 young (3-month old) and 8 aged (30-month old¿equivalent to a ~80-year old human) C57BL/6 mice. We measured their VOR response to whole-body static tilts and during 0.1¿10¿Hz whole-body sinusoidal and transient rotations before and after VOR adaptation training. Our data revealed minimal differences in static counter-tilt response between young and aged mice, but a significant deficit in baseline VOR gain in aged mice during transient rotations. Moreover, aged mice had a significant decrease in short-term VOR adaptation, particularly for training that sought to decrease the VOR response.
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2017 |
Tu L, Poppi L, Rudd J, Cresswell ET, Smith DW, Brichta A, Nalivaiko E, 'Alpha-9 nicotinic acetylcholine receptors mediate hypothermic responses elicited by provocative motion in mice', Physiology and Behavior, 174 114-119 (2017) [C1] Hypothermic responses accompany motion sickness in humans and can be elicited by provocative motion in rats. We aimed to determine the potential role in these responses of the eff... [more] Hypothermic responses accompany motion sickness in humans and can be elicited by provocative motion in rats. We aimed to determine the potential role in these responses of the efferent cholinergic vestibular innervation. To this end, we used knockout (KO) mice lacking a9 cholinoreceptor subunit predominantly expressed in the vestibular hair cells and CBA strain as a wild-type (WT) control. In WT mice, circular horizontal motion (1¿Hz, 4¿cm radius, 20¿min) caused rapid and dramatic falls in core body temperature and surface head temperature associated with a transient rise in the tail temperature; these responses were substantially attenuated in KO mice; changes were (WT vs. KO): for the core body temperature¿-¿5.2¿±¿0.3 vs. -¿2.9¿±¿0.3¿°C; for the head skin temperature¿-¿3.3¿±¿0.2 vs. -¿1.7¿±¿0.2¿°C; for the tail skin temperature¿+¿3.9¿±¿1.1 vs¿+¿1.1¿±¿1.2¿°C. There was a close correlation in the time course of cooling the body and the surface of the head. KO mice also required 25% more time to complete a balance test. We conclude: i) that the integrity of cholinergic efferent vestibular system is essential for the full expression of motion-induced hypothermia in mice, and that the role of this system is likely facilitatory; ii) that the system is involvement in control of balance, but the involvement is not major; iii) that in mice, motion-induced body cooling is mediated via increased heat flow through vasodilated tail vasculature and (likely) via reduced thermogenesis. Our results support the idea that hypothermia is a biological correlate of a nausea-like state in animals.
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2016 |
Parkinson GM, Dayas CV, Smith DW, 'Perturbed cholesterol homeostasis in aging spinal cord', Neurobiology of Aging, 45 123-135 (2016) [C1] The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by a... [more] The spinal cord is vital for the processing of sensorimotor information and for its propagation to and from both the brain and the periphery. Spinal cord function is affected by aging, however, the mechanisms involved are not well-understood. To characterize molecular mechanisms of spinal cord aging, microarray analyses of gene expression were performed on cervical spinal cords of aging rats. Of the metabolic and signaling pathways affected, cholesterol-associated pathways were the most comprehensively altered, including significant downregulation of cholesterol synthesis-related genes and upregulation of cholesterol transport and metabolism genes. Paradoxically, a significant increase in total cholesterol content was observed-likely associated with cholesterol ester accumulation. To investigate potential mechanisms for the perturbed cholesterol homeostasis, we quantified the expression of myelin and neuroinflammation-associated genes and proteins. Although there was minimal change in myelin-related expression, there was an increase in phagocytic microglial and astrogliosis markers, particularly in the white matter. Together, these results suggest that perturbed cholesterol homeostasis, possibly as a result of increased inflammatory activation in spinal cord white matter, may contribute to impaired spinal cord function with aging.
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2016 |
James MH, Quinn RK, Ong LK, Levi EM, Smith DW, Dickson PW, Dayas CV, 'Rapamycin reduces motivated responding for cocaine and alters GluA1 expression in the ventral but not dorsal striatum', European Journal of Pharmacology, 784 147-154 (2016) [C1] The mechanistic target of rapamycin complex 1 (mTORC1) regulates synaptic protein synthesis and therefore synaptic function and plasticity. A role for mTORC1 has recently been dem... [more] The mechanistic target of rapamycin complex 1 (mTORC1) regulates synaptic protein synthesis and therefore synaptic function and plasticity. A role for mTORC1 has recently been demonstrated for addiction-related behaviors. For example, central or intra-accumbal injections of the mTORC1 inhibitor rapamycin attenuates several indices of cocaine-seeking including progressive ratio (PR) responding and reinstatement. These behavioral effects are associated with decreased mTORC1 activity and synaptic protein translation in the nucleus accumbens (NAC) and point to a possible therapeutic role for rapamycin in the treatment of addiction. Currently, it is unclear whether similar behavioral and biochemical effects can be achieved by administering rapamycin systemically, which represents a more clinically-appropriate route of administration. Here, we assessed the effects of repeated, systemic administration of rapamycin (10 mg/kg, i.p.) on PR responding for cocaine. We also assessed whether systemic rapamycin was associated with changes in measures of mTORC1 activity and GluA1 expression in the ventral and dorsal striatum. We report that systemic rapamycin treatment reduced PR breakpoints to levels comparable to intra-NAC rapamycin. Systemic rapamycin treatment also reduced phosphorylated p70S6K and GluA1 AMPARs within the NAC but not dorsal striatum. Thus, systemic administration of rapamycin is as effective at reducing drug seeking behavior and measures of mTORC1 activity compared to direct accumbal application and may therefore represent a possible therapeutic option in the treatment of addiction. Possible caveats of this treatment approach are discussed.
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2016 |
Murray HC, Maltby VE, Smith DW, Bowden NA, 'Nucleotide excision repair deficiency in melanoma in response to UVA', Experimental Hematology and Oncology, 5 (2016) [C1] Background: The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely characterised. UVA and UVB com... [more] Background: The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely characterised. UVA and UVB components of sunlight are implicated in melanomagenesis; however the majority of studies have focused on the effects of UVB and UVC light. Interestingly, melanoma tumour sequencing has revealed an overrepresentation of mutations signature of unrepaired UV-induced DNA damage. Repair of UVA-induced DNA damage is thought to occur primarily through the Nucleotide Excision Repair (NER) pathway, which recognises and repairs damage either coupled to transcription (Transcription Coupled Repair; TCR), or through global genome scanning (Global Genome Repair; GGR). Current literature suggests NER is deficient in melanoma, however the cause of this remains unknown; and whether reduced NER activity in response to UVA may be involved in melanoma development remains uncharacterised. In this study we aimed to determine if melanoma cells exhibit reduced levels of NER activity in response to UVA. Methods: Melanocyte and melanoma cell lines were UVA-irradiated, and DNA damage levels assessed by immunodetection of Cyclobutane Pyrimidine Dimer (CPD) and (6-4) Photoproduct [(6-4)PP] lesions. Expression of NER pathway components and p53 following UVA treatment was quantified by qPCR and western blot. Results: UVA did not induce detectable induction of (6-4)PP lesions, consistent with previous studies. Repair of CPDs induced by UVA was initiated at 4 h and complete within 48 h in normal melanocytes, whereas repair initiation was delayed to 24 h and >40 % of lesions remained in melanoma cell lines at 48 h. This was coupled with a delayed and reduced induction of GGR component XPC in melanoma cells, independent of p53. Conclusion: These findings support that NER activity is reduced in melanoma cells due to deficient GGR. Further investigation into the role of NER in UVA-induced melanomagenesis is warranted and may have implications for melanoma treatment.
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2015 |
McIlroy DJ, Bigland M, White AE, Hardy BM, Lott N, Smith DW, Balogh ZJ, 'Cell necrosis-independent sustained mitochondrial and nuclear DNA release following trauma surgery', JOURNAL OF TRAUMA AND ACUTE CARE SURGERY, 78 282-288 (2015) [C1]
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2015 |
Quinn RK, Brown AL, Goldie BJ, Levi EM, Dickson PW, Smith DW, et al., 'Distinct miRNA expression in dorsal striatal subregions is associated with risk for addiction in rats', Translational Psychiatry, 5 (2015) [C1] Recently, we published data using an animal model that allowed us to characterize animals into two groups, addiction vulnerable and addiction resilient, where we identified that a... [more] Recently, we published data using an animal model that allowed us to characterize animals into two groups, addiction vulnerable and addiction resilient, where we identified that addiction/relapse vulnerability was associated with deficits in synaptic plasticityassociated gene expression in the dorsal striatum (DS). Notable was the strong reduction in expression for activity-regulated cytoskeleton-associated protein (Arc) considered a master regulator of synaptic plasticity. In the present study, we confirmed that Arc messenger RNA was significantly decreased in the DS, but importantly, we identified that this reduction was restricted to the dorsomedial (DMS) and not dorsolateral striatum (DLS). There is recent evidence of microRNA (miRNA)-associated posttranscriptional suppression of Arc and animal models of addiction have identified a key role for miRNA in the regulation of addiction-relevant genes. In further support of this link, we identified several differentially expressed miRNA with the potential to influence addiction-relevant plasticity genes, including Arc. A key study recently reported that miR-212 expression is protective against compulsive cocaine-seeking. Supporting this hypothesis, we found that miR-212 expression was significantly reduced in the DMS but not DLS of addiction-vulnerable animals. Together, our data provide strong evidence that miRNA promote ongoing plasticity deficits in the DS of addiction-vulnerable animals.
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2015 |
Parkinson GM, Dayas CV, Smith DW, 'Age-related gene expression changes in substantia nigra dopamine neurons of the rat.', Mech Ageing Dev, 149 41-49 (2015) [C1]
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2015 |
Thomas J, Garg ML, Smith DW, 'Effects of dietary supplementation with docosahexaenoic acid (DHA) on hippocampal gene expression in streptozotocin induced diabetic C57Bl/6 mice', Journal of Nutrition and Intermediary Metabolism, 2 2-7 (2015) [C1] A body of evidence has accumulated indicating diabetes is associated with cognitive impairments. Effective strategies are therefore needed that will delay or prevent the onset of ... [more] A body of evidence has accumulated indicating diabetes is associated with cognitive impairments. Effective strategies are therefore needed that will delay or prevent the onset of these diabetes-related deficits. In this regard, dietary modification with the naturally occurring compound, docosahexaenoic acid (DHA), holds significant promise as it has been shown to have anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The hippocampus, a limbic structure involved in cognitive functions such as memory formation, is particularly vulnerable to the neurotoxic effects related to diabetes, and we have previously shown that streptozotocin-induced diabetes alters hippocampal gene expression, including genes involved in synaptic plasticity and neurogenesis. In the present study, we explored the effects of dietary supplementation with DHA on hippocampal gene expression in C57Bl/6 diabetic mice. Diabetes was established using streptozotocin (STZ) and once stable, the dietary intervention group received AIN93G diet supplemented with DHA (50 mg/kg/day) for 6 weeks. Microarray based genome-wide expression analysis was carried out on the hippocampus of DHA supplemented diabetic mice and confirmed by real time polymerase chain reaction (RT-qPCR). Genome-wide analysis identified 353 differentially expressed genes compared to non-supplemented diabetic mice. For example, six weeks of dietary DHA supplementation resulted in increased hippocampal expression of Igf II and Sirt1 and decreased expression of Tnf-a, Il6, Mapkapk2 and ApoE, compared to non-supplemented diabetic mice. Overall, DHA supplementation appears to alter hippocampal gene expression in a way that is consistent with it being neuroprotective in the context of the metabolic and inflammatory insults associated with diabetes.
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2014 |
James 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, 39 1694-1702 (2014) [C1]
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Nova | |||||||||
2014 |
McIlroy 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, 29 1133.e1-1133.e5 (2014) [C1] Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondri... [more] Introduction: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component. Methods: Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition. Results: Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component. Conclusions: Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications.
|
Nova | |||||||||
2014 |
Thomas 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) [C1] Diabetes is associated with cognitive impairment and brain aging, with alterations in hippocampal neurogenesis and synaptic plasticity implicated in these changes. As the prevalen... [more] Diabetes is associated with cognitive impairment and brain aging, with alterations in hippocampal neurogenesis and synaptic plasticity implicated in these changes. As the prevalence of diabetes continues to rise, readily implemented strategies are increasingly needed in order to protect the brain's cognitive functions. One possibility is resveratrol (RES) (3,5,4- trihydroxystilbene), a polyphenol of the phytoalexin family that has been shown to be protective in a number of neuropathology paradigms. In the present study, we sought to determine whether dietary supplementation with RES has potential for the protection of cognitive functions in diabetes. Diabetes was induced using streptozotocin, and once stable, animals received AIN93G rodent diet supplemented with RES for 6 weeks. Genome-wide expression analysis was conducted on the hippocampus and genes of interest were confirmed by quantitative, real-time polymerase chain reaction. Genome-wide gene expression analysis of the hippocampus revealed that RES supplementation of the diabetic group resulted in 481differentially expressed genes compared to non-supplemented diabetic mice. Intriguingly, gene expression that was previously found significantly altered in the hippocampus of diabetic mice, and that is implicated in neurogenesis and synaptic plasticity (Hdac4, Hat1, Wnt7a, ApoE), was normalized following RES supplementation. In addition, pathway analysis revealed Jak-Stat signaling was the most significantly enriched pathway. The Jak-Stat pathway induces a pro-inflammatory signaling cascade, and we found most genes involved in this cascade (e.g. Il15, Il22, Socs2, Socs5) had significantly lower expression following RES supplementation. These data indicate RES could be neuroprotective and beneficial for the maintenance of cognitive function in diabetes. © 2014 Elsevier Inc.
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2014 |
Parkinson GM, Dayas CV, Smith DW, 'Increased mitochondrial DNA deletions in substantia nigra dopamine neurons of the aged rat.', Current aging science, 7 155-160 (2014) [C2]
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2014 |
James MH, Campbell EJ, Walker FR, Smith DW, Richardson HN, Hodgson DM, Dayas CV, 'Exercise reverses the effects of early life stress on orexin cell reactivity in male but not female rats', Frontiers in Behavioral Neuroscience, 8 (2014) [C1]
|
Nova | |||||||||
2013 |
Balogh ZJ, McIlroy DJ, Smith DW, Hansbro PM, 'The origin and the role of mitochondrial DNA in postinjury inflammation', Journal of Critical Care, 28 1099-1100 (2013) [C3]
|
Nova | |||||||||
2013 |
Thomas 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]
|
Nova | |||||||||
2013 |
Thomas 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] The hippocampus is an important brain structure for multiple cognitive functions, including memory formation. It is particularly sensitive to insults, such as stress, ischemia, an... [more] The hippocampus is an important brain structure for multiple cognitive functions, including memory formation. It is particularly sensitive to insults, such as stress, ischemia, and aging; all of these can affect hippocampal and therefore cognitive function. To understand the potential of diet for the preservation of hippocampal function, we investigated the effects of dietary supplementation with resveratrol (RES) or docosahexaenoic acid (DHA), or their combination, on hippocampal gene expression in adult C57BL/6 mice. Animals in the supplemented group received either 50 mg/kg/day of RES or DHA, while the combination group received 50 mg/kg/day of each supplement. Dietary supplements were mixed with the AIN93G diet, and supplementation lasted 6 weeks. The control group received AIN93G diet alone for the same period. At the end of the experiment, the hippocampi were processed for genome-wide gene expression and pathway analyses. Most of the genes that were significantly altered were associated with inflammatory responses as determined by pathway analysis. RES-supplemented animals showed decreased expression of IL-6 ( P=001), MAPKapk2 ( P=015), and increased expression for PI3. KR2 ( P=034) and Wnt7a ( P=004) expression. DHA-supplemented animals showed a decreased IL-6 ( P=003) and an increased Wnt7a ( P=003) expression. Animals on the combination diet showed a decreased IL-6 ( P=005) and Apolipoprotien E ( ApoE) ( P=035) expression. Our findings demonstrate that hippocampal gene expression is significantly altered by all three dietary supplementation regimes. Moreover, our analysis indicates that RES and DHA likely exert their beneficial effects through antiinflammatory mechanisms. © 2013 Elsevier Inc.
|
Nova | |||||||||
2013 |
Cahif 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]
|
Nova | |||||||||
2013 |
Brown AL, Day TA, Dayas CV, Smith DW, 'Purity and Enrichment of Laser-Microdissected Midbrain Dopamine Neurons', BIOMED RESEARCH INTERNATIONAL, 2013 (2013) [C1]
|
Nova | |||||||||
2012 |
Barreto 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]
|
Nova | |||||||||
2012 |
Dayas 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]
|
Nova | |||||||||
2011 |
James 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]
|
Nova | |||||||||
2011 |
James 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]
|
Nova | |||||||||
2011 |
Brown 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]
|
Nova | |||||||||
2010 |
James 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]
|
Nova | |||||||||
2009 |
McInerny 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]
|
Nova | |||||||||
2009 |
Brown AL, Smith DW, 'Improved RNA preservation for immunolabeling and laser microdissection', RNA: A Publication of the RNA Society, 15 2364-2374 (2009) [C1]
|
Nova | |||||||||
2007 |
Smith DW, Jinnah HA, 'Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice', Metabolic Brain Disease, 22 39-43 (2007) [C1]
|
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Show 53 more journal articles |
Conference (15 outputs)
Year | Citation | Altmetrics | Link | |||||
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2015 |
Dickinson S, Smith K, Bigland M, Smith D, Jobling P, Graham B, 'Morphological analysis of microglial and astrocyte populations in the superficial dorsal horn of spinal cord in aged mice', JOURNAL OF NEUROCHEMISTRY, Cairns, AUSTRALIA (2015) [E3]
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2014 |
Khan SI, Hübner PP, Smith DW, Brichta AM, Migliaccio AA, 'Ageing reduces vestibulo-ocular reflex adaptation in mice J Vestib Res', Journal of Vestibular Research: Equilibrium and Orientation: an international journal of experimental and clinical vestibular science (2014) [E3]
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2013 |
Bigland 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]
|
Nova | ||||||
2012 | Parkinson 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] | |||||||
2012 |
James 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]
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2012 |
Thomas 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]
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2012 |
Brown 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]
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2012 |
Dayas 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]
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2011 |
Thomas 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]
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2011 |
Barreto 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]
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2010 |
Thomas 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]
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2007 | McInerny 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] | |||||||
Show 12 more conferences |
Grants and Funding
Summary
Number of grants | 21 |
---|---|
Total funding | $5,866,640 |
Click on a grant title below to expand the full details for that specific grant.
20221 grants / $144,000
Understanding how cholesterol dysregulation in the aging brain causes Alzheimer's Disease$144,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Doug Smith, Mr Ethan Cresswell |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2022 |
Funding Finish | 2024 |
GNo | G2200946 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20182 grants / $907,715
Cognitive inflexibility and the development of pathological habits in brain diseases$897,715
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Chris Dayas, Professor Bernard Balleine, Dr Laura Corbit, Associate Professor Doug Smith, Professor Murray Cairns, Dr Billy Chieng, Professor Paul Kenny |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2018 |
Funding Finish | 2020 |
GNo | G1700396 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
Investigation of Age-Related Neuro-Inflammatory and Neuro-Vascular Changes in the Central Nervous System$10,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Mr Mitchell Cummins, Associate Professor Doug Smith |
Scheme | Greaves Family Postgraduate Top Up Scholarship in Medical Research |
Role | Lead |
Funding Start | 2018 |
Funding Finish | 2018 |
GNo | G1900117 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20171 grants / $25,000
Cholesterol metabolism in the ageing brain – implications for dementia$25,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Doug Smith |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2017 |
GNo | G1700349 |
Type Of Funding | C3300 – Aust Philanthropy |
Category | 3300 |
UON | Y |
20152 grants / $45,000
Maintaining our cognitive abilities as we grow old: preventing the effects of ageing on the brain$25,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Doug Smith, Professor Rohan Walker |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2015 |
Funding Finish | 2015 |
GNo | G1500078 |
Type Of Funding | Grant - Aust Non Government |
Category | 3AFG |
UON | Y |
Dizzy and Deaf - restoring signals from the inner ear$20,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Associate Professor Rebecca Lim, Professor Alan Brichta, Conjoint Professor Robert Callister, Associate Professor Doug Smith |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2015 |
Funding Finish | 2015 |
GNo | G1501395 |
Type Of Funding | Grant - Aust Non Government |
Category | 3AFG |
UON | Y |
20131 grants / $35,000
Leica TP 1020 Automatic Tissue Processor for histology applications$35,000
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Pradeep Tanwar, Professor Eileen McLaughlin, Professor Xu Dong Zhang, Conjoint Professor Robert Callister, Associate Professor Phillip Dickson, Professor Hubert Hondermarck, Doctor Jean-Marie Sontag, Professor Dirk Van Helden, Associate Professor Doug Smith, Associate Professor Phil Jobling, Associate Professor Estelle Sontag, Associate Professor Paul Tooney, Associate Professor Susan Hua, Doctor Janet Bristow, Professor Jay Horvat, Prof LIZ Milward, Professor Adam McCluskey, Professor Brett Nixon, Associate Professor Rebecca Lim, Professor Alan Brichta |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2013 |
Funding Finish | 2013 |
GNo | G1201185 |
Type Of Funding | Other Public Sector - Commonwealth |
Category | 2OPC |
UON | Y |
20122 grants / $313,375
The effects of ageing on the peripheral vestibular system. Can ageing-related functional decline be reduced or prevented?$298,375
Funding body: The Garnett Passe and Rodney Williams Memorial Foundation
Funding body | The Garnett Passe and Rodney Williams Memorial Foundation |
---|---|
Project Team | Associate Professor Doug Smith |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2014 |
GNo | G1100935 |
Type Of Funding | C3200 – Aust Not-for Profit |
Category | 3200 |
UON | Y |
2011 Emerging Research Leaders Program$15,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Associate Professor Doug Smith |
Scheme | Emerging Research Leaders Program |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2012 |
GNo | G1200307 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20111 grants / $25,000
Brain Mechanisms Conferring Psychostimulant Addiction$25,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Chris Dayas, Emeritus Professor Peter Dunkley, Associate Professor Doug Smith |
Scheme | Near Miss Grant |
Role | Investigator |
Funding Start | 2011 |
Funding Finish | 2011 |
GNo | G1001052 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20104 grants / $649,000
Laser microdissection microscopy system for cell and development biology$350,000
Funding body: ARC (Australian Research Council)
Funding body | ARC (Australian Research Council) |
---|---|
Project Team | Professor Eileen McLaughlin, Conjoint Professor Keith Jones, Distinguished Emeritus Professor John Aitken, Professor Brett Nixon, Doctor Shaun Roman, Professor Alan Brichta, Doctor Rick Thorne, Associate Professor Doug Smith, Aprof DAVID McCurdy, Emeritus Professor Ray Rose, Professor Christopher Grof, Emeritus Professor Leonie Ashman, Professor Gordon Burns, Professor Brett Graham, Associate Professor Paul Tooney, Laureate Professor Roger Smith, Professor Paul Foster, Professor Trevor Day, Conjoint Professor Robert Callister |
Scheme | Linkage Infrastructure Equipment & Facilities (LIEF) |
Role | Investigator |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | G0190369 |
Type Of Funding | Scheme excluded from IGS |
Category | EXCL |
UON | Y |
Laser microdissection microscopy system for cell and development biology$215,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Eileen McLaughlin, Conjoint Professor Keith Jones, Distinguished Emeritus Professor John Aitken, Professor Brett Nixon, Doctor Shaun Roman, Professor Alan Brichta, Doctor Rick Thorne, Associate Professor Doug Smith, Aprof DAVID McCurdy, Emeritus Professor Ray Rose, Professor Christopher Grof, Emeritus Professor Leonie Ashman, Professor Gordon Burns, Professor Brett Graham, Associate Professor Paul Tooney, Laureate Professor Roger Smith, Professor Paul Foster, Professor Trevor Day, Conjoint Professor Robert Callister |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | G1000874 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
Laser microdissection microscopy system for cell and development biology (HMRI contribution towards 2010 ARC LIEF grant)$50,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Eileen McLaughlin, Conjoint Professor Keith Jones, Distinguished Emeritus Professor John Aitken, Professor Brett Nixon, Doctor Shaun Roman, Professor Alan Brichta, Doctor Rick Thorne, Associate Professor Doug Smith, Aprof DAVID McCurdy, Emeritus Professor Ray Rose, Professor Christopher Grof, Emeritus Professor Leonie Ashman, Professor Gordon Burns, Professor Brett Graham, Associate Professor Paul Tooney, Laureate Professor Roger Smith, Professor Paul Foster, Professor Trevor Day, Conjoint Professor Robert Callister |
Scheme | Equipment Grant |
Role | Investigator |
Funding Start | 2010 |
Funding Finish | 2010 |
GNo | G1000144 |
Type Of Funding | Other Public Sector - State |
Category | 2OPS |
UON | Y |
ABI 7500 Real Time PCR System $34,000
Funding body: NHMRC (National Health & Medical Research Council)
20081 grants / $538,500
Dopamine mechanisms conferring resilience to depression: A new antidepressant target$538,500
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Trevor Day, Emeritus Professor Peter Dunkley, Professor David Pow, Associate Professor Doug Smith |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2008 |
Funding Finish | 2010 |
GNo | G0187604 |
Type Of Funding | Aust Competitive - Commonwealth |
Category | 1CS |
UON | Y |
20072 grants / $40,000
Vulnerability to depression: the role of dopamine pathways$20,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Professor Trevor Day, Emeritus Professor Peter Dunkley, Associate Professor Doug Smith, Professor David Pow |
Scheme | Near Miss Grant |
Role | Investigator |
Funding Start | 2007 |
Funding Finish | 2007 |
GNo | G0187196 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
Characterisation of the brain mechanisms linking vulnerability to stress and vulnerability to drug addiction$20,000
Funding body: Hunter Medical Research Institute
Funding body | Hunter Medical Research Institute |
---|---|
Project Team | Professor Trevor Day, Professor Chris Dayas, Associate Professor Doug Smith |
Scheme | Project Grant |
Role | Investigator |
Funding Start | 2007 |
Funding Finish | 2007 |
GNo | G0187255 |
Type Of Funding | Contract - Aust Non Government |
Category | 3AFC |
UON | Y |
20042 grants / $13,679
Characterisation of age-related gene expression changes in midbrain dopamine neurons$12,000
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Associate Professor Doug Smith |
Scheme | New Staff Grant |
Role | Lead |
Funding Start | 2004 |
Funding Finish | 2004 |
GNo | G0184998 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
Society for Neuroscience Annual Meeting, 23-27 October 2004$1,679
Funding body: University of Newcastle
Funding body | University of Newcastle |
---|---|
Project Team | Associate Professor Doug Smith |
Scheme | Travel Grant |
Role | Lead |
Funding Start | 2004 |
Funding Finish | 2004 |
GNo | G0184814 |
Type Of Funding | Internal |
Category | INTE |
UON | Y |
20031 grants / $2,489,371
Genetic aberrations in HPRT deficiency$2,489,371
Funding body: National Institute of Neurological Disorders (NIH)
Funding body | National Institute of Neurological Disorders (NIH) |
---|---|
Project Team | Theodore Friedmann |
Scheme | Project |
Role | Investigator |
Funding Start | 2003 |
Funding Finish | 2007 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20011 grants / $641,000
Array screening for Lesch-Nyhan disese$641,000
Funding body: NICH (NIH)
Funding body | NICH (NIH) |
---|---|
Project Team | Theodore Friedmann |
Scheme | R21 |
Role | Investigator |
Funding Start | 2001 |
Funding Finish | 2003 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Research Supervision
Number of supervisions
Current Supervision
Commenced | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2023 | PhD | Understanding How Aging Impacts The Proteome To Make The Brain Susceptible To Developing Alzheimer’s Disease. | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2021 | PhD | Understanding the Early Stages of Alzheimer’s Disease | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2018 | PhD | Effect of Ageing on Central Nervous System Cholesterol Homeostasis | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
Past Supervision
Year | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2023 | PhD | Classical Approaches versus Modern Molecular Techniques to Dissect Neuronal Heterogeneity in the Dorsal Horn: Opposite Ends of the Same Spectrum? | PhD (Human Physiology), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2022 | PhD | Investigating the Processes of Age-Related Inflammation in the Central Nervous System | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2020 | PhD | Model Perturbations of Glial Synaptomodulatory and Immune Functions | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2019 | PhD | Ageing of the Inner Ear Vestibular Organs | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2018 | PhD | The Role of Mitochondrial DNA in the Post-Injury Inflammatory Response Following Major Trauma | PhD (Medicine), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2016 | PhD | Ageing of the Somatic Motor Nervous System: A Nuclear and Mitochondrial Genome Perspective | PhD (Medical Biochemistry), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2015 | Masters | Nucleotide Excision Repair of UVA-Induced DNA Damage: Regulation in Sunlight-Induced Melanoma | M Philosophy (Medical Genetic), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2014 | PhD | The Role of Cocaine- and Amphetamine-Regulated Transcript (CART) and Orexin in Drug-Seeking and Addiction-Related Behaviours | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2013 | PhD | Effects of Anti-Inflammatory Bioactives on Diabetes-Induced Changes in Cognition-Related Gene Expression in the Hippocampus | PhD (Medical Biochemistry), College of Health, Medicine and Wellbeing, The University of Newcastle | Co-Supervisor |
2012 | PhD | Molecular Correlates of Dopamine Signalling in Addiction Vulnerability | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2012 | PhD | Dopaminergic Pathway Imbalance in the Neurobiology of Depression | PhD (Anatomy), College of Health, Medicine and Wellbeing, The University of Newcastle | Principal Supervisor |
2006 | Honours | Role of mitochondrial D-loop in aging brain | Medical Science, University of Newcastle | Principal Supervisor |
Associate Professor Doug Smith
Position
Associate Professor
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing
Focus area
Anatomy
Contact Details
douglas.smith@newcastle.edu.au | |
Phone | 0468473659 |
Mobile | 0468473659 |
Fax | N/A |
Office
Room | MS511 |
---|---|
Building | Medical Sciences |
Location | Callaghan University Drive Callaghan, NSW 2308 Australia |