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PhD Project Opportunities at the Menzies Research Institute Tasmania, University of
Tasmania
Research at the Menzies Research Institute Tasmania (Menzies) is organised around five
themes that focus on the major diseases affecting the Tasmanian community. A number of
PhD project opportunities are available in each theme, as summarised below. More detail for
each project is provided on subsequent pages.
More information on Menzies and the five research Themes is available on-line at
www.menzies.utas.edu.au
Public Health & Primary Care
Our public health and primary care research team seeks to better prevent and manage
important population health problems. Projects address a broad range of conditions including
cardiovascular disease, type-2 diabetes, cancer, multiple sclerosis and depression. Several
projects are investigating how lifestyle factors (e.g. smoking, physical activity, diet, alcohol
consumption and sun exposure), obesity and hormones in childhood and early adulthood
affect the risk of developing disease later in life. Research in the public health area includes
epidemiology, behavioural science, environmental health, biostatistics and health economics.
Established partnerships with the Tasmanian State Government and management of the
Tasmanian Cancer Registry and Tasmanian Data Linkage Unit ensure a focus on applied
research.
Current projects available in this theme include:
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ADVENT (Anxiety Depression & heart rate Variability in cardiac patients: Evaluating
the impact of Negative emotions on functioning after Twenty four-months) (Dr Kristy
Sanderson)
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Alcohol consumption from childhood to adulthood and its associations with health
status (Professor Alison Venn and others)
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Assessment of goodness-of-fit of binary and multinomial regression models (Associate
Professor Leigh Blizzard)
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Australia-wide analysis of the risks and costs of bicycle accidents (Professor Andrew
Palmer)
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Childhood origins of depressive and anxiety disorders (Professor Alison Venn and
others)
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Chronic disease benchmarking in Tasmania (Associate Professor Leigh Blizzard)
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Clinical and genetic factors that influence the onset and progression of MS (Professor
Bruce Taylor)
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Depression in the workplace (Dr Kristy Sanderson)
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Development of a digitised screening tool for the prediction of cardiovascular disease
risk (Dr Costan Magnussen and Dr Russell Thomson)
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Diet quality, metabolomics and cardio-metabolic risk (Professor Alison Venn and
others)
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Epidemiology of Multiple Sclerosis. Several projects available, including identifying
modifiable factors of the conversion to MS and MS progression (Dr Ingrid van der Mei
and Professor Bruce Taylor)
PhD Project List
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An institute of the University of Tasmania
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Genetics of vitamin D (Dr Ingrid van der Mei)
Long-term reproductive health outcomes in tall girls treated with high-dose estrogen to
reduce their adult height (Professor Alison Venn)
Modifiers of cardio-metabolic risk in the overweight and obese (Professor Alison Venn
and others)
Patterns of sedentary behaviour and cardio-metabolic risk (Professor Alison Venn and
others)
Predictors and consequences of pre-hypertension and pre-diabetes in young adults
(Professor Alison Venn and others)
The genetic and environmental factors that affect conversion to and progression in MS
(Professor Bruce Taylor)
The impact of job losses on the physical and mental health of Tasmanians (Dr Kristy
Sanderson)
Vitamin D research that builds the evidence-base for new sun exposure
recommendations in Australia (Dr Ingrid van der Mei)
Neurodegenerative Disease/Brain Injury
Using cutting-edge tools, our neuroscientists aim to understand the mechanisms underlying
the brain's response to trauma (e.g. road accidents and falls) and diseases such as dementia
including Alzheimer's disease, multiple sclerosis, Parkinson's disease and motor neuron
disease. This research will assist in the development of new ways to diagnose, prevent or treat
these devastating disorders that affect hundreds of thousands of Australians each year.
Current projects available in this theme include:
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Can the brain’s endogenous progenitor/stem cells make new cells for brain repair? (Dr
Kaylene Young)
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Do primary cilia play a central role in regulating neural progenitor cell behaviour and
function in the adult brain? (Dr Kaylene Young)
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How do oligodendroglial cells replenish their ER calcium stores? (Dr Kaylene Young)
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New oligodendrocytes are added to the adult central nervous system – what is their
function? (Dr Kaylene Young)
Cardio-metabolic Health & Diseases
The primary aim of the cardiometabolic group is to reduce the burden of cardiovascular and
metabolic disease on our community.
The group uses interventions targeted at identifying and preventing the development of
obesity, insulin resistance, type-2 diabetes, hypertension and heart disease. Particular areas of
interest include blood pressure assessment, assessment of large and small blood vessels
functioning and cardiac imaging in heart disease.
The team use a broad set of research techniques from laboratory models, clinical and
population health studies and clinical interventions to discover new ways to prevent the
progression of cardio-metabolic disease.
Current projects available in this theme include:
PhD Project List
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An institute of the University of Tasmania
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Development and application of a prediction model for readmission to hospital with
heart failure (Professor Tom Marwick)
Impaired adipose tissue blood flow in obesity and the development of hypoxia (Dr
Steve Richards, Dr Michelle Keske and Professor Stephen Rattigan)
Incorporation of right ventricular evaluation in decision-making regarding pulmonary
hypertension (Professor Tom Marwick)
Microvascular blood flow and metabolic regulation in skeletal muscle (Professor
Stephen Rattigan)
Prevention of heart failure based on screening and treatment of subclinical LV
dysfunction (Professor Tom Marwick)
Quality control in cardiovascular imaging interpretation (Professor Tom Marwick)
Strategies for prevention of cardiotoxicity from cancer therapies (Professor Tom
Marwick)
Musculoskeletal Health & Diseases
Research in the musculoskeletal theme optimises Tasmania's unique population
characteristics to investigate musculoskeletal disease, with a particular emphasis on
osteoarthritis, osteoporosis and ankylosing spondylitis. Epidemiological research into
musculoskeletal disease helps us understand the impact of arthritis and other musculoskeletal
conditions on both the individual and the community, so the best medical care can be
developed and delivered where it is needed. Volunteer participant-based clinical trials are a
key feature of this area.
Current projects available in this theme include:
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Vitamin D effects on osteoarthritis (VIDEO) study (Associate Professor Changhai
Ding)
Cancer, Genetics & Immunology
Research conducted within this Theme aims to elucidate the underlying genetic and
epigenetic changes that underpin complex diseases such as cancer; and secondly to
understand the immune response during manifestation of these diseases. At present the group
is studying genetic susceptibility to prostate cancer and blood cancers, such as leukaemia. In
addition, the team is looking at the immune response in the context of cancer including the
Tasmanian devil facial tumour disease, infectious diseases and autoimmune diseases with a
particular interest in lupus and multiple sclerosis.
Currently available projects in this theme include:
Immunology
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Comprehensive analysis of Vitamin D receptor expression in immune cells and of its
role in autoimmunity (Collaboration with Professor Bruce Taylor and Associate
Professor Helmut Butzkoeven) (Professor Heinrich Korner)
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Role of TNF in the regulation of the adaptive T cell response in Leishmaniasis
(Professor Heinrich Korner)
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The chemokine CCL20 and its cognate receptor CCR6 in T-B cell collaboration and
germinal centre response: Relevance for human autoimmunity? (Professor Heinrich
Korner)
PhD Project List
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An institute of the University of Tasmania
Genetic and Epigenetic drivers of complex disease (includes statistical genetics)
There are current projects available in this area. Please contact Associate Professor Jo
Dickinson, Theme Leader, to discuss any future opportunities – [email protected]
Devil Facial Tumour Disease (DFTD)
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Identification and characterisation of DFTD tumour-associated antigens using
proteomics (Professor Greg Woods)
PhD Project List
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An institute of the University of Tasmania
Supervisor: Associate Professor Leigh Blizzard (2 projects)
Research Theme: Public Health & Primary Care
Research Area: Biostatistics and Biostatistics/Epidemiology
Email: [email protected] Phone: +61 (0)3 6226 7719
The primary role of the biostatisticians is to provide statistical advice and support to other
researchers at the Institute. In consequence they are involved in a wide range of research
collaborations that span each of the five Research Themes.
Research Interests:
In statistical research, Associate Professor Blizzard has contributed to developments in loglink modelling of binary, multinomial and ordinal outcomes of follow-up and cross-sectional
studies. Recently he has established a statistical research program in assessment of goodnessof-fit of log-link models in collaboration with Professor David Hosmer, a noted international
authority. The significance of this research has been recognised with a NHMRC Project
Grant, a Population Health Career Development Award and a Population Health Career
Development Fellowship. Associate Professor Blizzard also has expertise in population
survey methodology with multiple tested statistical software developments and applications
for analysis of population surveys.
Student Background:
The student would be mostly suitable for this project if she/he has a background of clinical
medicine.
Projects:
There are projects currently available in this area. Some of them include:
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Assessment of goodness-of-fit of binary and multinomial regression models. The
proposed research builds on an established research program in a continuing
collaboration with a noted international authority in the field to extend summary
measures of goodness-of-fit developed for logistic regression models to binary and
multinomial log-link models. Future work is to develop summary measures for models
with other links and/or error distributions, and to develop statistical approaches and
testing strategies to detect lack of fit at the level of individual observations.
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Chronic disease benchmarking in Tasmania. The first phase of the proposed work
involves the use of hospital separation and clinical costing data to estimate, and monitor
trends in, the prevalence of hospital-treated chronic disease (HTCD) in Tasmania. The
second phase involves estimation of within-hospital resource use by HTCD patients
with an eventual goal of determining levels and costs of avoidable hospitalisations and
complications and developing methodology to monitor trends and evaluate
interventions.
PhD Project List
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An institute of the University of Tasmania
Supervisor: Associate Professor Changhai Ding
Research Theme: Musculoskeletal Health & Diseases
Research Area: Musculoskeletal Epidemiology
Email: [email protected] Phone: +61 (0)3 6226 7730
Associate Professor Ding has published over 100 manuscripts in international peer-reviewed
journals with an h index of 26. He has received > 10 awards including "Future Fellowship" by
Australian Research Council (ARC) and "Career Development Award" by National Health &
Medical Research Council (NHMRC).
Research Interests:
Associate Professor Ding's research interests centre around the epidemiological and clinical
investigation of osteoarthritis using modern techniques such as magnetic resonance imaging.
He is looking at the metabolic and inflammatory mechanisms of osteoarthritis and
osteoporosis, and is interested in evaluating new therapies on osteoarthritis and other
inflammatory diseases. Currently, he is undertaking a clinical trial to determine if vitamin D
supplementation can slow disease progression of knee osteoarthritis.
Student Background:
The student would be mostly suitable for this project if she/he has a background of clinical
medicine.
Project 1: Vitamin D Effects on Osteoarthritis (VIDEO) study
VIDEO study is a randomised, placebo-controlled double-blind clinical trial investigating
whether correcting vitamin D deficiency using vitamin D supplements will slow loss of
cartilage and thus worsening of knee osteoarthritis. 400 patients have been, or will be,
randomly allocated to vitamin D supplementation (50,000 IU monthly) or placebo for 2 years,
with the major outcome being cartilage loss between these two groups. Other knee structural
changes including tibial bone area, bone marrow lesions and meniscal pathology (assessed by
MRI), and lower limb muscle strength at baseline and 2 years later will also be determined as
outcome measures. This study has been supported by the National Health and Medical
Research Council (NHMRC).
PhD Project List
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An institute of the University of Tasmania
Supervisor: Professor Heinrich Korner
Research Theme: Cancer, Genetics & Immunology
Research Area: Immunology
Email: [email protected]
Phone: +61 (0)3 6226 4698
Research Interests:
Professor Korner is a New Star Professor at the Menzies Research Institute Tasmania. His
researched is focused on Cellular Immunology and Infection Immunology.
Student Background:
These research projects are most likely to be successfully completed by candidates with a life
sciences background.
Project 1: Role of TNF in the regulation of the adaptive T cell response in Leishmaniasis
Leishmaniasis is a significant tropical and subtropical disease caused by protozoan parasites
of the genus Leishmania. The clinical spectrum of leishmaniasis ranges from relatively benign
skin lesions to terribly disfiguring mucosal lesions and, finally, to systemic visceral disease,
which is fatal if left untreated In experimental cutaneous leishmaniasis, the infection of
C57BL/6 (B6.WT) mice with Leishmania (L.) major causes a cutaneous lesion while an
infection of the BALB/c strain causes progressive systemic disease. Due to this genetic
dichotomy experimental leishmaniasis is a classic model used to explore the adaptive immune
response to pathogens. While much has been learned using this model of adaptive immune
responses there is still no vaccine for any major parasitic disease in general and leishmaniasis
in particular. We have an immune system that seems to respond to a parasitic infection with a
limited protective response and accepts a low level presence of parasitic pathogens due to an
array of immune evasive mechanisms, which allows the pathogens, for example, to survive
inside a phagolysosome. However, it is also in the interest of the host to curtail the immune
response to these challenges, because a strong immune response that would extinguish the
pathogens could lead to immunopathology and extensive damage to the host. As a
consequence, there is no sterile cure in parasitic infections such as leishmaniasis, but instead
we see relatively benign infections and long-lasting persistence, which is controlled by the
immune system but harbours the possibility of reactivation. A cytokine that is involved in this
immune control is TNF. In TNF-negative mice, which succumb rapidly to leishmaniasis, we
find the scenario that at a crucial point in the immune response T cell activation increases and
effector T cell populations start to enlarge. Interestingly, the population of regulatory T cells
(Treg) is overrepresented at the late stage of disease. We propose to use these highly
susceptible mice to further investigate the T cell response in the absence of TNF, investigate
the potential to initiate protection and analyse the impact of the enlarged Treg population on
the protective immune response.
Hypothesis
TNF influences the adaptive immune response by controlling numbers of Tregs and effector T
cells and facilitating a protective but not overreaching anti-parasitic immune response.
PhD Project List
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An institute of the University of Tasmania
Aims
1:
To analyze the role of TNF in a) T cell activation, b) the generation of effector T cells
and Tregs and c) the maintenance of the suppressive function of Tregs during infection
with high- and low-virulent L. major strains using TNF, TNFR1 and 2-deficient mice.
2:
To follow the individual fate of single antigen-specific T cells and Tregs in L. major
infected mice using transgenic L. major variants for infection.
3:
To analyze the potential of low-virulent L. major strains to induce a protective response.
4:
To analyze the role of Tregs cells in L. major-infected B6.TNF-/- mice using a genetic
model of Treg depletion and IL-10 blockade.
Project 2: The chemokine CCL20 and its cognate receptor CCR6 in T-B cell
collaboration and germinal centre response: Relevance for human autoimmunity?
Background: The CC-chemokine receptor 6 (CCR6) is expressed constitutively on naïve B
cells at an intermediate level and is strongly upregulated on pre-germinal centre (GC) B cells
after activation. The CIAs laboratory investigated the potential role of CCR6 in B cell
differentiation in vivo. We showed that B cells of CCR6-deficient mice displayed a significant
acceleration in the GC response after immunization accompanied by an increase in the
number of GC and, subsequently, in IgG antibodies with low-affinity to NP-KLH. The
phenotype was associated with an up-regulation in the number of follicular T helper cells
(TFH) and could also be observed using other immunogens such as sheep red blood cells. This
phenotype as consequence of a chemokine receptor deficiency represents intriguing
correlations to described autoimmune phenotypes as an increase of GC numbers and
increased numbers of TFH have been described in the murine B cell associated autoimmune
disease models for Systemic Lupus Erythematosus (SLE), sanroque (Roquinsan/san) and
generalized lympho-proliferative disease (gld). In humans, increased numbers of GC and
increased TFH in the blood are characteristic for SLE patients.
Hypotheses
A) CCR6 and its ligand CCL20 facilitate an exclusion of potential GC B cells from entering
follicles. B) Failure of this CCR6-mediated selection results in abundant but low quality GC
response.
Aims
1:
To establish an adoptive transfer mouse model to dissect the kinetics of intracellular and
surface expression of CCR6 and CCL20 on mouse B and T FH cells and analyse the
location of CCR6+ and CCL20+ B and TFH cells.
2:
To investigate the function of CCR6 and CCL20 in the formation of cognate T -B
conjugates and analyse gene expression in those cells and cell conjugates
3:
To dissect the contribution of CCR6 and CCL20 to antibody class switch and somatic
hypermutation.
4:
To analyse the balance of cell death and proliferation in the GC in the absence of CCR6.
PhD Project List
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An institute of the University of Tasmania
Project 3: Comprehensive analysis of Vitamin D receptor expression in immune cells
and of its role in autoimmunity (Collaboration with Professor Bruce Taylor and
Associate Professor Helmut Butzkoeven)
Vitamin D receptor (VDR) is a cytoplasmic receptor for its ligand 1,25-dihydroxyvitamin D
(1,2,5(OH)2D3), which is metabolized from a precursor, 25-hydroxyvitamin D (2,5(OH)D3).
VDR has been shown to be involved in the modulation of the gene expression of hundreds of
genes including immunologically relevant genes. While the precursor can be supplemented by
the appropriate diet the major source of biologically active vitamin D is still the synthesis in
the skin driven by sunlight. In higher latitudes of the planet a seasonal deficiency of vitamin
D is therefore not unusual. This deficiency has been associated with the occurrence and the
relapse frequency of Multiples Sclerosis (MS) and with general seasonal immunodeficiency.
Despite the important role of VDR a comprehensive analysis of its expression level and its
immunological role in human blood leukocytes is missing.
Hypothesis
The hypothesis to be tested in this project is that the level of VDR expression and its
interaction with bioactive vitamin D in leukocytes is correlated with the occurrence of MS.
Aims
1.
Analysis of VDR expression and immune-modulatory activity in blood leukocytes of
controls and MS patients using flow cytometry and bioassays.
2.
Generation of mixed bone marrow mouse chimeras using different precursor cells from
VDR deficient mice and wildtype mice and analysis of these chimeras in the mouse
model of MS, Experimental Autoimmune Encephalomyelitis.
PhD Project List
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An institute of the University of Tasmania
Supervisors: Dr Costan Magnussen and Dr Russell Thomson
Research Theme: Public Health & Primary Care
Research Area: Cardiovascular epidemiology
Email: [email protected]
Phone: +61 (0)3 6226 7762
Email: [email protected] Phone: +61 (0)3 6226 4611
Dr Magnussen is a NHMRC Early Career Research Fellow at the Menzies Research Institute
Tasmania (MRIT) and Adjunct Professor of cardiovascular epidemiology at the University of
Turku, Finland. He has published in excess of 45 papers in the last five years, many in leading
international journals including 11 publications in journals with impact factors >10.
Dr Thomson is a Postdoctoral Research Fellow at the MRIT and the Institute for Marine and
Antarctic Studies at the University of Tasmania. He has published in excess of 41 papers,
many in leading international journals including 7 publications in journals with impact factors
>10.
Research Interests:
Dr Magnussen’s key research interests have focused on the paediatric origin of adult
cardiometabolic disease.
Dr Thomson key research interests include the implementation of classification and regression
trees for the purposes of risk prediction.
Student Background:
Outstanding candidates would normally be able to demonstrate a background in statistics,
programming and health sciences.
Project: Development of a digitised screening tool for the prediction of cardiovascular
disease risk.
Although the consequences of cardiovascular disease such as heart attack and stroke do not
usually occur before middle age, the processes underlying these complications begin early in
life. It has been thought that to achieve greater reduction in cardiovascular disease events,
primordial and primary prevention of the risk factors that predispose to the disease need to be
implemented much earlier in life, even in childhood. Therefore, the challenge is to develop
innovative tools that allow screening of children to identify those at risk of developing the
disease in the future who would benefit most from primordial or primary prevention.
The successful candidate will have the opportunity to use data from a major international
collaboration, the International Childhood Cardiovascular Cohort (i3C) Consortium
(http://i3cconsortium.org), to: 1) use regression trees to build models that examine the effects
of multiple childhood risk factors on cardio-metabolic outcomes in adulthood; 2) predict the
risk of cardio-metabolic outcomes for any child, given their risk factors; and 3) develop a
digitised screening tool (app) that can be applied in the preventive health care setting.
PhD Project List
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An institute of the University of Tasmania
Data from the i3C consortium have been published in many high-ranking international
journals, including the New England Journal of Medicine and the top ranked cardiovascular
journals worldwide, Circulation and the Journal of the American College of Cardiology.
Therefore, the successful candidate will have the opportunity to use a unique dataset and
examine clinically relevant questions with supervision from researchers with a strong track
record of publishing in high-impact journals.
References:
Dwyer T, Sun C, Magnussen CG, Raitakari OT, Schork NJ, Venn A, Burns TL, Juonala M,
Steinberger J, Sinaiko AR, Prineas RJ, Davis PH, Woo JG, Morrison JA, Daniels SR, Chen
W, Srinivasan SR, Viikari JS, Berenson GS. (2012) Cohort Profile: The International
Childhood Cardiovascular Cohort (i3C) Consortium. International Journal of Epidemiology.
[Epub ahead of print]
Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, Chen W, Srinivasan SR,
Daniels SR, Kähönen M, Laitinen T, Taittonen L, Berenson GS, Viikari JSA, Raitakari OT.
(2010) The influence of age on associations between childhood risk factors and carotid
intima-media thickness in adulthood. The Cardiovascular Risk in Young Finns Study, the
Childhood Determinants of Adult Health Study, the Bogalusa Heart Study and the Muscatine
Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation.
Touw, W.G., Bayjanov, J.R., Overmars, L., Backus, L., Boekhorst, J., Wels, M. & van Hijum,
S.A.F.T. (2012) Data mining in the Life Sciences with Random Forest: a walk in the park or
lost in the jungle? Briefings in Bioinformatics.
PhD Project List
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An institute of the University of Tasmania
Supervisor: Professor Thomas H Marwick MBBS (Hons), PhD, MPH
Research Theme: Cardio-metabolic Health & Diseases
Research Area: Cardiovascular imaging, clinical effectiveness
Email: [email protected]
Phone: +61 (0)3 6226 7703
Professor Marwick is Director of Menzies Research Institute Tasmania and also works as a
Cardiologist at Royal Hobart Hospital. Over the last 25 years, he has published extensively
and supervised over 20 postgraduate research students and many clinical trainees in
cardiology and cardiovascular imaging.
Research Interests:
Professor Marwick's research interests involve the use of cardiovascular imaging (mainly
echocardiography but also magnetic resonance and CT) to better understand the pathogenesis
of disease and especially to inform clinical decision-making. Although based strongly in
clinical physiology, his current studies are linked with population health and include
components of outcomes research and cost-effectiveness. He collaborates widely across
specialties and geographically across Australia, North America, Europe and Asia.
Student Background:
These research projects are most likely to be successfully completed by candidates with a
clinical background (eg. medicine, health services research, sonography/radiography, nursing,
psychology).
Project 1: Development and application of a prediction model for readmission to
hospital with heart failure
Acute heart failure (HF) is related to ~100,000 admissions/y and $1 billion spending in
Australia. It accounts for ~1% of all hospital separations in Australia, and ~10% of those due
to circulatory disease, a frequency of 1.6-2.0 per 1000 population. Readmissions to hospital
after HF are frequent. In Tasmania, preliminary data from the Clinical Informatics & Business
Intelligence Unit of the Dept of Health and Human Services (DHHS) show 1945 admissions
since FY 2008, i.e. about 500 index admissions per year with HF as the primary diagnosis.
The 30 day readmission rate for repeat HF (or related) is 25% but ranges geographically and
is 36% at Royal Hobart Hospital (RHH, likely related to complexity). There are similar
numbers of non-HF admissions. These findings are analogous to readmission rates of 30%
within 2 months in the USA and UK. Based on yearly readmission costs of US$17.4 billion in
the US, the Center for Medicare and Medicaid Services (CMS) has advocated using 30 day
mortality and readmission as one method of measuring overall quality of hospital based care
for heart failure.
This work seeks to reduce heart failure (HF) admissions and costs by;
i)
Evaluating current performance in HF readmission, and use data linkage to identify sites
where community-based service delivery would offer most benefit to reduce HF
readmission
ii) Developing a risk algorithm for HF readmission, including psychosocial determinants.
PhD Project List
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An institute of the University of Tasmania
iii)
iv)
v)
Combining the knowledge derived from data linkage and the risk algorithm to devise a
new means of providing a HF disease-management program (DMP), calibrated to risk
assessment, and performing a clinical trial to define the merits of this approach.
An evaluation of cost-effectiveness of this intervention.
Presentation of educational activities to community-based providers.
Project 2: Strategies for prevention of cardiotoxicity from cancer therapies
As cancer therapies and survival have improved, millions of patients treated with cardiotoxic
therapy are now cancer survivors. Prolongation of survival resulting from cancer treatment
allows patients to live long enough for cardiac toxicity to become the main determinant of
quality of life, and in some cases premature mortality – in fact, for early stage breast cancer, a
patient is more likely to die from heart disease than cancer. Preliminary (unpublished) work
from the SEER-Medicare database in the USA showed a cancer cohort treated from 2002-7 to
have a 5 year incidence of heart failure of 18%.
This study seeks to show that information from cardiac imaging surveillance leads to the use
of adjunctive cardioprotective therapy that will limit the development of reduced ejection
fraction (EF) at 1 year post chemotherapy (primary outcome), and interruptions to planned
chemotherapy and the development of heart failure in follow-up (secondary outcomes). The
primary hypothesis is that the use of cardioprotective agents, administered in response to
subclinical left ventricular (LV) dysfunction detected on surveillance imaging, prevents the
progression to reduction of LVEF or overt heart failure.
Project 3: Prevention of heart failure based on screening and treatment of subclinical
LV dysfunction
Despite major advances, the outlook for advanced heart failure (HF) remains dire. In the hope
that early recognition and treatment may prevent the progression of disease, two early stages
have been defined. Stage A heart failure is characterized by patients having risk factors for
HF including hypertension, type 2 diabetes mellitus (T2DM), the metabolic syndrome (MS),
family history of HF or atherosclerotic disease, whereas stage B heart failure is identified
when patients have evidence of actual heart disease. The distinction of stages A and B is very
significant, because their therapeutic implications are quite different. The management of
stage A relates mainly to the control of hypertension and underlying risk factors, with specific
therapy (angiotensin converting enzyme inhibitors [ACEi] or angiotensin receptor blockers
[ARB]) limited to patients in whom these agents are indicated on the basis of T2DM or
vascular disease. Based on evidence gathered in patients with asymptomatic LV dysfunction,
ACEi or ARB and beta blockers are indicated in all stage B patients, in the belief that HF risk
will be decreased by 20-30%. The goal of this study is to define the benefit of a surveillance
program to identify stage B HF in “at risk” patients with stage A HF, by showing that medical
therapy for Stage B patients found in this way reduces their subsequent presentations with
HF.
The primary objective of this work is to show that information from a screening program for
LV dysfunction in at-risk patients combined with cardioprotective therapy based on screening
will limit the development of heart failure (HF) after a minimum of 2 years. The secondary
objectives are to document a treatment benefit with respect to exercise capacity, symptom
status and resource utilization. We will seek to achieve this by a randomised controlled trial in
at-risk patients. Realisation of this objective would provide evidence for changes in clinical
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An institute of the University of Tasmania
guidelines to include both a screening program as well as justify pharmacological intervention
in patients with abnormal screening tests.
Project 4: Quality control in cardiovascular imaging interpretation
Continuous quality assessment and implementation of methods to improve interpretation of
imaging studies is an important responsibility of all imaging laboratories. However, the
literature on methods to assess and/or improve IOV and accuracy of visual EF quantification
is limited. Using topics such as aortic regurgitation, RV and LV function, we have previously
developed a process of quality exercises, based on group-based case reviews along with crossmodality comparisons. To date, this has been done mainly on a single-centre basis.
However, there remain several problems. Provision of a lengthy structured educational
session may be organizationally challenging at many institutions, and providing an
intervention uniformly to all members of a laboratory can be difficult. We are therefore
seeking methods to deliver this process over the internet. We also week to identify a subgroup
of individuals who may benefit the most from the intervention.
PhD Project List
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An institute of the University of Tasmania
Supervisor: Professor Andrew Palmer
Research Theme: Pubic Health & Primary Care
Research Area: Health Economics, Epidemiology
Email: [email protected] Phone: +61 (0)3 6226 7729
Professor Palmer is the Head of Health Economics at the Menzies Research Institute
Tasmania. Professor Palmer has extensive experience in the area of health economics and
outcomes research, and is a widely published, well-known and respected health economist.
Research Interests:
Professor Palmer has conducted research and published extensively in the area of health
economics and the modeling of diseases including diabetes, nephropathy, osteoporosis,
alcoholism, growth hormone deficiency, rheumatoid arthritis, cardiovascular disease, endstage renal failure and oncology.
Student Background:
This project will be most suited to a candidate with health economics and /or epidemiological
background.
Project 1: Australia-wide analysis of the risks and costs of bicycle accidents
Tasmanians are exposed to dangerous and potentially fatal cycling conditions on a daily basis
as they commute by bicycle or cycle for health. There is frequent public debate on the hazards
of cycling on Tasmanian roads, as evidenced by a recent Australian Associated Motor
Insurers Limited (AAMI) survey and the wave of responses published in the Mercury
newspaper in February 2010. Dangerous traffic was cited as a major deterrent to cycling.
Furthermore, the large majority of vehicle drivers reported seeing cyclists as a nuisance. This
is a potentially fatal cocktail of attitudes that deter the use of bicycles as a form of commuting
or exercise for health improvement.
Local and state governments are under increasing pressure to provide adequate and safe
infrastructure to improve the safety and acceptability of cycling in Australia. Public health
and environmental research encourages cycling as both a health-giving activity and a means
of reducing the state’s dependence on the car as a means of transport, in an era dominated by
concerns about carbon emissions, global warming and peak oil.
This study will lend support to creating the necessary infrastructure that is required to provide
health benefits to the community.
Professor Andrew Palmer has over 18 years’ experience in the area of health economics and
outcomes research, and is a widely published, well-known and respected health economist. He
recently published an analysis of the costs of all cycling accident (and other) claims under the
Motor Accident Insurance Board (MAIB) scheme from 1991 until 2010 in an international
peer-reviewed journal. Andrew is currently supervising a pilot study to measure the risk and
associated economic burden of bicycle accidents in Tasmania. An accurate assessment of
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An institute of the University of Tasmania
accident rates and associated costs is needed to inform discussions with local and state
government in order to improve cycling infrastructure and the safety of both cyclists and
motorists. Current cycling infrastructure in Tasmania is far behind that of other cities in states.
Tasmania currently has 2.2km of cycling network for every 100km of road network. This is
just over a third of the second lowest-ranked area Perth (6.6km).
The ultimate outcome of this research will be improved safety conditions for cyclists and a
reduced economic burden in Australia.
As a pilot study, the information gained has formed the basis for further state and national
studies to advance and promote the body of knowledge of cycling risks and benefits.
Moreover, an understanding of the scope of the healthcare burden to Australia, represented by
cycling accidents, is vital in order to identify potential cost-offsets that may occur through
reduced costs of cycling accident injuries from improvement in safety measures and
infrastructure. The proposed research project builds on a pilot Tasmanian-based project
initiated by Professor Palmer. It will provide the first insights into Australian cycling habits,
accident rates and costs of cycling accidents Australia-wide, will allow comparisons between
states and territories, and will shed light on the balance between the health benefits of cycling
versus risk of accidents and their associated costs.
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An institute of the University of Tasmania
Supervisor: Professor Stephen Rattigan
Research Theme: Cardio-metabolic Health & Diseases
Research Area: Muscle Metabolism
Email: [email protected] Phone: +61 (0)3 6226 2671
Professor Rattigan is Deputy Director of Menzies Research Institute Tasmania. Over the last
25 years, he has published extensively and supervised over 25 postgraduate research students.
Research Interests:
Obesity, hypertension and type 2 diabetes are major health problems for Australia and are
likely to increase in the 21st century. One of the common features of these conditions is
insulin resistance in skeletal muscle. Professor Rattigan's research has focussed on the factors
that regulate glucose metabolism in skeletal muscle and have led to the important finding that
blood flow regulation within muscle is critical to the normal responses to insulin. Impairment
of normal blood flow distribution within muscle can lead to insulin resistance and it is his
current hypothesis that such defects are the early events associated with obesity and
hypertension that contribute to type 2 diabetes.
Student Background:
This research project is most likely to be successfully completed by candidates with a
biomedical, clinical or bioengineering background with a mathematical interest (eg.
physiology, biochemistry, or biophysics).
Project: Microvascular blood flow and metabolic regulation in skeletal muscle
Vasomotion and the resultant flowmotion of blood flow in tissues is a fundamental
physiological phenomenon that has been poorly understood. This project combines the use of
two innovative techniques of laser Doppler flowmetry and real-time contrast-enhanced
ultrasound that enables determination of flowmotion, with methodology that provides
information on tissue metabolism in skeletal muscle in vivo. A major aim of this project will
be to gain new knowledge about how flowmotion regulates the microvascular blood flow and
nutrient delivery to muscle and the control of muscle metabolism. As flowmotion is a
fundamental physiological process, the outcomes will be important in a number of medical
conditions, such as sarcopenia, vascular derived dementia, athletic performance, injury
recovery, sepsis and critical care where blood flow and nutrient delivery are critical
determinants of these pathological conditions. In particular this project will have a focus on
understanding the development of insulin resistance, the underlying condition associated with
obesity, hypertension and type 2 diabetes. The PhD candidate will be expected to have a
strong background in physiology and mathematics and be expected to undertake studies in
experimental animal models and human clinical research.
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An institute of the University of Tasmania
Supervisors: Dr Steve Richards, Dr Michelle Keske, Professor Stephen Rattigan
Research Theme: Cardio-metabolic Health & Diseases
Research Area: Diabetes and obesity
Email: [email protected] Phone: +61 (0)3 6226 2673
In healthy subjects, in addition to its well-known metabolic effects in liver and muscle, insulin
stimulates increased blood flow in muscle and adipose tissue, enhancing delivery of substrates
and hormones to the underlying cells. Our research has established that impaired
microvascular responses to insulin contribute significantly to muscle insulin resistance in type
2 diabetes. Our group has expertise in measuring metabolic responses to insulin in rats and
humans and has also developed a number of techniques for simultaneous quantification of
microvascular blood flow responses, including contrast-enhanced ultrasound (CEU) and 1methylxanthine metabolism (1,2). Although the relationship between microvascular blood
flow and the metabolic responses to insulin in health and obesity or insulin resistance was
established by the group for skeletal muscle the same may hold true for adipose tissue. This
project involves application of these techniques to study adipose tissue changes in obese and
insulin resistant rat models.
Research Interests:
The Muscle Diabetes Research Group has developed techniques for measuring microvascular
blood flow within muscle in humans and animals. Importantly, the group (including Professor
Stephen Rattigan and Dr Michelle Keske) has shown muscle blood flow to be an important
determinant of the sensitivity of muscle to insulin, and that reduced blood flow responses to
insulin contribute to insulin resistance, and possibly the development of type 2 diabetes. Dr
Richards' research aims to determine why the microvascular actions of insulin are impaired in
insulin resistant animal models, and aims to find ways of enhancing muscle blood flow
responses to insulin. Two current methods for achieving this focus on (i) the role of the
adipocyte-derived hormone adiponectin, and (ii) augmenting the biochemical signalling used
by insulin to increase muscle microvascular blood flow, namely the nitric oxide-cyclic GMP
pathway, with a view to the development of novel therapeutics.
Student Background:
This research project is most likely to be successfully completed by candidates with a
biomedical, clinical or bioengineering background with a mathematical interest (eg.
physiology, biochemistry, or biophysics).
Project: Impaired adipose tissue blood flow in obesity and the development of hypoxia
It is now widely recognised that the insulin resistance that precedes type 2 diabetes results
from two main factors that block insulin signal transduction: (i) accumulation of fatty acid
metabolites in insulin-sensitive tissues other than adipose tissue (eg liver, muscle) (3) and (ii)
increased levels of circulating cytokines due to chronic, low grade inflammation, particularly
in adipose tissue (4). Inflammation in adipose tissue in obesity is due to macrophage
activation and recruitment, and it has recently been recognised that activation of a
transcription factor, Hypoxia Inducible Factor 1αa (HIF1α) is the critical event precipitating
this process (5). Why hypoxia develops in adipose tissue in obesity is not altogether clear, but
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An institute of the University of Tasmania
we hypothesise that impaired blood flow responses to insulin result in intermittent hypoxia, as
a result of increased energy demands from triglyceride synthesis not being matched by a
compensatory increase in oxygen supply. A corollary of the inadequate blood flow during
insulin is that triglyceride synthesis may also be impaired, reducing lipid storage in adipocytes
and promoting lipid accumulation in tissues such as liver and muscle. We further hypothesise
that these changes (inflammatory, lipid storage) are more severe in visceral than subcutaneous
adipose tissue, explaining the stronger association between insulin resistance and visceral
obesity.
This project aims to:
1.
Determine the effect of blood flow on metabolism and expression of proinflammatory
cytokines in adipose tissue.
2.
Compare the vascular actions of insulin in adipose tissue, and compare development of
vascular and metabolic dysfunction, hypoxia, inflammation, adipocyte hypertrophy, and
vascular rarefaction during the onset of obesity.
3.
Determine whether impairment of the vascular actions of insulin contributes to
increased susceptibility of visceral adipose tissue to metabolic and proinflammatory
changes in obesity.
Techniques
Adipose tissue blood flow in rats will be measured by CEU and the effects of restricting blood
flow by injection of microspheres on expression of HIF1a and cytokines will be assessed by
semi-quantitive (real time) RT-PCR of mRNA expression and Western blotting for protein
levels. The metabolic effects of impaired blood flow on insulin action will be assessed in
normal and obese adipose tissue from [3H]2-deoxyglucose and [14C]triolein uptake, and from
high energy phosphate levels by HPLC. Adipocyte hypertrophy and capillary rarefaction will
be assessed by standard immunohistochemical techniques. All measurements will be
performed simultaneously in both subcutaneous (inguinal) and visceral (epididymal) adipose
tissue depots at different time points flowing introduction of animals placed to high fat diets.
References
1.
Clark, M. G., Wallis, M. G., Barrett, E. J., Vincent, M. A., Richards, S. M., Clerk, L. H.,
and Rattigan, S. (2003) Am J Physiol Endocrinol Metab 284, E241-258
2.
Rattigan, S., Bussey, C. T., Ross, R. M., and Richards, S. M. (2007) Microcirculation
14, 299-309
3.
Boden, G., and Shulman, G. I. (2002) Eur J Clin Invest 32 Suppl 3, 14-23
4.
Hotamisligil, G. S. (2003) Int J Obes Relat Metab Disord 27 Suppl 3, S53-55
5.
Halberg, N., Khan, T., Trujillo, M. E., Wernstedt-Asterholm, I., Attie, A. D., Sherwani,
S., Wang, Z. V., Landskroner-Eiger, S., Dineen, S., Magalang, U. J., Brekken, R. A.,
and Scherer, P. E. (2009) Mol Cell Biol 29, 4467-4483
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An institute of the University of Tasmania
Supervisor: Dr Kristy Sanderson
Research Themes: Public Health & Primary Care
Research Area: Psychiatric Epidemiology
Email: [email protected]
Phone: +61 (0)3 6226 4724
Research Interests:
Dr Sanderson's research focuses on quantifying and reducing the individual and economic
burden of mental disorders and related chronic diseases. Her work has been recognized
through selection for the National Health and Medical Research Council “Ten of the Best
Research Projects 2011” and from support by an Australian Research Council Future
Fellowship.
Student Background:
As outlined for each project.
Project 1: Depression in the workplace
Depression is the leading cause of disease-burden in high-income countries like Australia and
is predicted to become the second cause of global burden by 2030. While there are many
effective treatments available for depression, the majority of sufferers remain undetected
and/or untreated. At least half of the people who experience depression and related disorders
are able to continue working, thus workplaces are an important avenue to explore
opportunities for reducing the high burden of these disorders. Using a number of data sources
including some funded by NHMRC our group is addressing questions such as:

What is the current prevalence of depressive and anxiety disorders in the Australian
workforce and has it changed over the past decade?

How much productivity loss (work disability) is associated with these disorders and
what does it cost? How much of this cost is borne by the employee?

How do managers perceive the impact of these disorders on workplace performance?

Why do these disorders seem to have such a strong association with “presenteeism”
(continuing to work when sick)?

Can continuing to work when sick actually worsen health?

How can we better manage presenteeism and what is the role of different health and
other professionals in this?

Do these issues have a greater impact in certain occupations or industries?
This research area is growing rapidly and there are substantial opportunities to make a
contribution from students with an interest/background in public health, health promotion,
epidemiology, or allied health.
Project 2: ADVENT
The ADVENT (Anxiety Depression & heart rate Variability in cardiac patients: Evaluating
the impact of Negative emotions on functioning after Twenty four-months) study is a
prospective cohort study investigating the interplay between psychosocial and biological
factors relevant to symptoms of depression and anxiety in post-MI patients at 12- and 24PhD Project List
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An institute of the University of Tasmania
months. Depression and anxiety commonly occur in patients with heart disease, particularly
those who have had a heart attack. Together they represent a large burden on the healthcare
system as well as individual patient’s lives. This study will help us to further understand the
complex biological and psychological relationships between depression/anxiety and heart
disease.
ADVENT is a NHMRC-funded project led by Monash University in collaboration with
Menzies Research Institute Tasmania, University of Melbourne, and Stanford University.
This project provides an opportunity to work with leading researchers in cardiology,
psychiatry, public health, and epidemiology.
The PhD opportunity at Menzies focuses on the following areas:
1) Methods for screening and diagnosis of mental health disorders in post-MI populations
2) Patterns of mental health symptoms in post-MI populations
3) Association of particular patterns of mental health symptoms with employment
outcomes and quality of life.
This project will be suitable for students with an interest/background in public health,
epidemiology, or allied health.
Project 3: The impact of job losses on the physical and mental health of Tasmanians
This project aims to investigate in Tasmania among working age adults: i) the temporal
association of job loss with hospital use and mortality; ii) the association of hospital use with
job loss; iii) whether these associations differ for urban versus rural/remote areas and by
prevailing economic climate. This study will use an ecological time series analysis using
existing employment and health statistics for Tasmania.
In Tasmania suicide is the leading cause of death in adults up to the age of 44 years, with
ischaemic heart disease the second leading cause of death from age 45 onwards. Tasmania has
had significant periods of job market contraction with rural and remote areas especially hardhit. The association between job loss and health may be because job loss contributes to
illness, illness contributes to job loss, or both. How soon any health affects appear from job
losses, and whether this varies by health outcome, is unknown. It is also unknown whether
any health outcomes differ between rural/remote and urban communities, or whether the
prevailing economic climate affects different health outcomes in different ways.
This project will be suitable for students with an interest/background in epidemiology,
statistics, or allied health.
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An institute of the University of Tasmania
Supervisor: Professor Bruce Taylor
Research Theme: Public Health & Primary Care
Research Area: Multiple Sclerosis & Statistical Genetics
Email: [email protected] Phone: +61 (0)3 6226 7704
Professor Taylor's research interests centre on the environmental and genetic factors that
influence the development and progression of multiple sclerosis. His previous students
include Dr Ingrid van der Mei, now a highly respected researcher investigating MS and
Vitamin D deficiencies in the population. Dr van der Mei advises the government on sun
exposure policy. Prof Taylor’s team is composed of a strong group of postdoctoral fellows
and research students. He works closely with Dr Jac Charlesworth a genetic bio informatician
and is a member of the governance committee of the Australian and New Zealand MS
Genetics consortium and the steering committee of the International MS genetics Consortium.
Consequently we have access to a unique highly curated data set of 5,000 MS GWAS
samples, and over 2,000 exome arrays. We also through collaborations as outlined have
access to cutting edge international MS genetic programmes.
Research Interests:
Professor Taylor’s research interests include:

Gene environment interactions in the onset and progression of MS.

The search for genetic rare variants that contribute to the onset and progression of MS.

The role of epigenetic changes in the onset and progression of MS.

The role of non coding variants in the onset and progression of MS.

The effect of environmental and personal factors on the progression of MS.
Student Background:
Students should have an interest in computational genetics, and some background in genetics
of complex disorders. They should have an interest in statistics and a background in
epidemiology public health for the non genetic projects. The student will learn how to analyse
complex databases using epidemiological processes and novel statistical methods and will be
involved in the development of analysis techniques for assessing causation in longitudinal
studies.
Project 1: The genetic and environmental factors that affect conversion to and
progression in MS
We host the largest longitudinal MS CIS study in the world, The Ausimmune/AUSLONG
study that has followed around 250 people with their first episode of MS for at least 5 years
and have just received funding to extend this study to 10 years. We have collected a wealth of
data on environmental and personal factors that may affect progression to definite MS and
modulate the rate of disability progression. As part of this project we will use the bespoke MS
chip to acquire exome array data and 200,000 additional SNPs from the immunochip project
to assess how genetic variance affects MS progression.
Project 2: Clinical and genetic factors that influence the onset and progression of MS
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An institute of the University of Tasmania
Utilising the large amount of environmental and genetic data in the AUSLONG study we are
looking for students to drive the analysis of this internationally highly regarded data set. This
will involve selecting factors that may putatively modulate the progression of MS and using
cutting edge genetic analyses determine the contribution of these factors to MS progression.
This study is unique in its design and outcome measures and will contribute significantly to
the world’s knowledge of MS progression.
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An institute of the University of Tasmania
Supervisor: Dr Ingrid van der Mei
Research Theme: Public Health & Primary Care
Research Area: Epidemiology
Email: [email protected]
Phone: +61 (0)3 6226 7710
Research Interests:
Dr van der Mei is an epidemiologist who focuses her research on vitamin D deficiency in the
general population and risk factors of the onset and progression of Multiple Sclerosis.
Student Background:
Project 1: The student needs to have a background in Epidemiology or Public Health and
needs to have an aptitude for statistics.
Project 2: The student needs to have a background in Genetics and a strong aptitude in
Genetic Statistics. The student also needs to understand, or be willing to learn, the field of
Epidemiology.
Title: Vitamin D deficiency in the general population
Vitamin D is a steroid hormone that is predominantly produced in the body when the skin is
exposed to the ultraviolet (UV) rays in sunlight. Vitamin D is required for optimal bone
health. While it was previously thought that vitamin D deficiency was uncommon in sunny
Australia, there is now evidence that it is more common than expected, even in healthy
individuals. In Tasmania, 67% of healthy Tasmanian adolescents and adults are vitamin D
deficient (<50 nmol/L) in winter and spring and 33% are deficient in summer and autumn.1-3
The recognition of vitamin D deficiency is important, because it causes a tension with the skin
cancer public health campaign. This work therefore aims to contribute to new public health
recommendations in relation to sun exposure and vitamin D.
AusD study
A multi-centre vitamin D study (Hobart, Canberra, Brisbane, Townsville) has been
conducting in 1002 healthy Australians. In each region, ~250 people of the general population
were enrolled, aged 18-70 years. Vitamin D levels were measured, as well as recent sun
exposure, sun behaviour, sun attitudes, skin type, vitamin D intake, muscle function, blood
pressure, use of medications and genes involved in the production of vitamin D. DNA was
collected for genotyping.
Project 1: Vitamin D research that builds the evidence-base for new sun exposure
recommendations in Australia
The AusD dataset is a rich dataset that can answer a large range of research questions such as:
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An institute of the University of Tasmania






What is the profile of people who are vitamin D deficient all year round?
How much time are different groups of people required to spend outside to maintain
vitamin D sufficiency in different times of the year?
Which factors influence how much time people spend outdoors or how much skin they
expose?
Can we predict how much time people need to spend outside based on the UV index?
Why is obesity a strong predictor of vitamin D levels?
How important is skin type as a predictor of vitamin D levels?
Sun exposure recommendations are likely to be tailored to location. There will be the
opportunity to conduct more in-depth analyses using the Hobart data and to translate this data
to new recommendations, together with the Cancer Council Tasmania.
Project 2: Genetics of vitamin D
Relatively little is known about the genes that influence serum vitamin D levels. While we
know that vitamin D levels are for a large part driven by environmental factors such as
ambient UV and sun exposure behaviour, Genome Wide Association Studies do not have data
on these environmental predictors of vitamin D. The AusD study will have both genotype and
environmental data available and can therefore examine the effect of genes on vitamin D after
taking into account the influence of the environmental factors. Moreover, genes are likely to
interact with these environmental factors in the production of vitamin D. Examining the
interplay between genes and environmental factors will substantially increase the knowledge
on the pathway of vitamin D.
The AusD provides the unique opportunity to examine:

Which genotypes are associated with vitamin D levels, after taking environmental
factors into account

Which genotypes modify the association between personal exposure to solar radiation
and vitamin D levels.

Which genotypes modify the association between body mass index and vitamin D
levels.
References
1.
van der Mei IA, Ponsonby AL, Engelsen O, et al. The high prevalence of vitamin D
insufficiency across Australian populations is only partly explained by season and
latitude. Environ Health Perspect. Aug 2007;115(8):1132-1139.
2.
van der Mei IA, Ponsonby AL, Dwyer T, et al. Vitamin D levels in people with multiple
sclerosis and community controls in Tasmania, Australia. J Neurol. May
2007;254(5):581-590.
3.
van der Mei IA, Dore D, Winzenberg T, Blizzard L, Jones G. Vitamin D deficiency in
Tasmania: A whole of life perspective. Intern Med J. Apr 5 2012.
PhD Project List
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An institute of the University of Tasmania
Supervisor: Dr Ingrid van der Mei and Professor Bruce Taylor
Research Theme: Public Health & Primary Care
Research Area: Epidemiology of Multiple Sclerosis
Email: [email protected]
Phone: +61 (0)3 6226 7710
Research Interests:
Dr van der Mei is an epidemiologist and Professor Taylor is a clinical researcher and
neurologist. Part of their research focuses on the risk factors of Multiple Sclerosis (MS) onset
and progression, for example sun exposure, infection load in early life and EBV infection.1-4
Dr van der Mei also examines how genes and environmental factors interact with each other
to cause disease.5,6
Student Background:
The PhD student is expected to have a background in epidemiology and statistics.
Project: Identifying modifiable factors of the conversion to MS and MS progression
Several projects are available suitable for PhD projecs
AusLong study
The study aims to predict prognosis after a first demyelinating event and aims to identify
modifiable lifestyle factors that influence progression. People with a first demyelinating event
have been followed for five years. The novel aspect internationally is the collection of data in
multiple domains - environmental, genetic, clinical, and magnetic resonance imaging.
Environmental data available includes sun exposure, vitamin D, Epstein-Barr virus markers,
exposure to chemicals, exposure to infections, stressful life events, immunisations, smoking,
dietary intake, and physical activity. Clinical data includes data on disability, fatigue, anxiety,
and depression. Knowledge of lifestyle factors that modify this debilitating disease empower
patients to delay conversion to MS (occurrence of a second episode of demyelination) and
limit the increase in disability. The ultimate aim is to create a predictive algorithm that will
encompass all these domains, which provides information on an individual prognosis for
patients and can guide treatment decisions.
Tasmanian MS Longitudinal Study
This study focuses on factors that modify the progression of MS (e.g. clinical progression,
onset of relapses, development of new brain lesions). A population-based sample of 200
people with established MS was followed 6-monthly for up to three years. Detailed data was
collected on disease progression, lifestyle factors, markers of viral reactivity and genes. A
number of papers have already been published using this rich data set. A novel finding was,
for example, that higher 25(OH)D levels are associated with a reduced hazard of relapse, each
10-nmol/L increase in 25(OH)D resulting in a 12% reduction in relapse risk.
The PhD student will have access to both datasets. They can choose a particular exposure, or
a number of exposures, and examine whether this is associated with the progression of MS. In
the AusLong study, one might examine whether an exposure (e.g. high antibody levels to
PhD Project List
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An institute of the University of Tasmania
Epstein-Barr virus) is associated with the conversion from a first demyelinating event to MS,
with the number of relapses or with the accumulation of clinical disability. Genetic data is
also available, allowing the examination of gene-environment interaction.
References:
1.
Simpson S, Jr., Taylor B, Blizzard L, et al. Higher 25-hydroxyvitamin D is associated
with lower relapse risk in multiple sclerosis. Ann Neurol. Aug 2010;68(2):193-203.
2.
Simpson S, Jr., Taylor B, Dwyer DE, et al. Anti-HHV-6 IgG titer significantly
predicts subsequent relapse risk in multiple sclerosis. Mult Scler. Jun 2012;18(6):799806.
3.
Lucas RM, Ponsonby AL, Dear K, et al. Current and past Epstein-Barr virus infection
in risk of initial CNS demyelination. Neurology. Jul 26 2011;77(4):371-379.
4.
Lucas RM, Ponsonby AL, Dear K, et al. Sun exposure and vitamin D are independent
risk factors for CNS demyelination. Neurology. Feb 8 2011;76(6):540-548.
5.
van der Mei IA, Ponsonby AL, Taylor BV, et al. Human leukocyte antigen-DR15, low
infant sibling exposure and multiple sclerosis: gene-environment interaction. Ann
Neurol. Feb 2010;67(2):261-265.
6.
van der Mei IA, Simpson S, Jr., Stankovich J, Taylor BV. Individual and joint action
of environmental factors and risk of MS. Neurol Clin. May 2011;29(2):233-255.
PhD Project List
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An institute of the University of Tasmania
Supervisor: Professor Alison Venn
Research Theme: Public Health & Primary Care
Research Area: Epidemiology (women’s reproductive health)
Email: [email protected] Phone: +61 (0)3 6226 7706
Research Interests:
Professor Venn is an epidemiologist with a long-standing interest in women’s reproductive
health. She has previously led major cohort studies investigating cancer risk associated with
infertility and IVF treatment, and of the long-term health effects of estrogen treatment of tall
girls. The Tall Girls Study was established to investigate the long-term health and
psychosocial consequences of treating tall girls with estrogen to reduce their growth and adult
height. It compared treated as well as untreated tall girls with follow-up for up to 40 years and
was conducted in collaboration with researchers at La Trobe University and the Murdoch
Children’s Research Institute. This treatment, while uncommon, has been given to several
thousand women around the world, mostly in the 1960s and 70s. The Tall Girls Study has
already investigated the long-term effects of treatment on mental wellbeing, fertility, breast
feeding and mammographic breast density as a marker of breast cancer risk.
Student Background:
This project would be suitable for a candidate with a background in women’s health,
midwifery, obstetrics or epidemiology.
Project 1: Long-term reproductive health outcomes in tall girls treated with high-dose
estrogen to reduce their adult height.
This project will investigate whether estrogen treatment for tall stature had any effect on the
following:
1.
The risk of miscarriage and ectopic pregnancy
2.
The risk of poor perinatal outcomes including preterm birth, low birthweight and
stillbirth.
3.
The incidence of gynaecological health problems
4.
The timing of menopause
PhD Project List
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An institute of the University of Tasmania
Supervisor: Professor Alison Venn and others
Research Theme: Public Health & Primary Care
Research Area: Epidemiology (cardiovascular disease and diabetes)
Email: [email protected] Phone: +61 (0)3 6226 7706
Professor Venn is an epidemiologist with a broad research program investigating the causes
and prevention of chronic disease. She has a particular focus on how factors in childhood
(overweight, blood pressure, blood lipids, smoking, physical activity, diet, and alcohol
consumption), and early adulthood affect the risk of developing cardiovascular disease and
diabetes later in life. Key resources for this work are the Childhood Determinants of Adult
Health (CDAH) study and an international collaboration, the i3C Consortium,
(www.i3Cconsortium.org) that pools data from similar cohorts in Finland and the USA.
The CDAH study team includes early and mid-career researchers with excellent research
records and specialist interests who are also able to provide supervision. They include: Dr
Verity Cleland (physical activity, obesity; socio-demographic determinants of health); Dr
Seana Gall (lifestyle, smoking, education); Dr Costan Magnussen (blood pressure, lipids,
vascular outcomes); Dr Kristy Sanderson (mental health); and Dr Kylie Smith (dietary
epidemiology).
The Childhood Determinants of Adult Health (CDAH) study is a cohort study with follow-up
at 20 and 25 years of 8498 children who participated in the 1985 Australian Schools Health
and Fitness Survey (ASHFS) when aged 7 to 15 years. Extensive measures of lifestyle,
physical characteristics, socio-demographic factors, blood biochemistry, mental health and
preclinical markers of cardiovascular disease and diabetes are available. To date this study has
resulted in more than 50 publications, many in very high ranking journals. Because the
CDAH data are so rich and extensive, a large number of PhD projects are available that would
suit candidates with backgrounds in any of the following: epidemiology; biostatistics; health,
clinical, or behavioural science; nutrition; human movement science or exercise physiology;
and psychology.
Examples of available PhD topics include the following:
1.
Predictors and consequences of pre-hypertension and pre-diabetes in young adults.
2.
Modifiers of cardio-metabolic risk in the overweight and obese
3.
Alcohol consumption from childhood to adulthood and its associations with health
status.
4.
Patterns of sedentary behaviour and cardio-metabolic risk
5.
Diet quality, metabolomics and cardio-metabolic risk
6.
Childhood origins of depressive and anxiety disorders
PhD Project List
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An institute of the University of Tasmania
Supervisor: Professor Greg Woods
Research Theme: Cancer, Genetics & Immunology
Research Area: Devil Facial Tumour Disease
Email: [email protected] Phone: +61 (0)3 6226 4832
Professor Woods completed an undergraduate degree (BSc(Hons)) at Monash University, a
postgraduate degree at the University of Tasmania (PhD) and has worked as a research
scientist in Toronto Canada, London England, and Edinburgh Scotland. He has an
international research profile having contributed significantly to the field of dendritic cells,
specifically in the area of Langerhans cells, cancer and the development of the neonatal skin
immune system, the effect of sunlight on the developing skin immune system and the role of
vitamin D3. Professor Woods was one of the first in the world to indicate that immature
dendritic cells induce suppression.
Research Interests:
Professor Woods' research interests are primarily aimed at how cancer cells escape detection
by the immune system. His major research programme is to evaluate the immune system of
the Tasmanian devil and to understand how devil facial tumour disease can be transmitted
between devils with the ultimate objective to develop strategies to protect devils from this
infectious cancer.
Student Background:
This project would suit a student who has experience in protein work, particularly proteomics.
Bioinformatics skills would be beneficial.
Project 1: Identification and characterisation of DFTD tumour-associated antigens
using proteomics
DFTD is a clonal tumour that originated from a Schwann cell. It is a cancer that is transmitted
between Tasmanian devils and once a devil is infected, the devil does not survive. One of our
aims is to develop a vaccine. The clonal nature of DFTD is an advantage that can be used to
identify tumour-associated antigens that are expressed on all DFTD cells in all devils, and
therefore represent ideal vaccine antigens.
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An institute of the University of Tasmania
Supervisors: Dr Kaylene Young, Professor David Small, Dr Lisa Foa
Research Theme: Neurodegenerative Disease/Brain Injury
Research Area: Laboratory of Molecular Neurobiology - Projects in neurodegeneration,
brain development and neural regeneration
Email: [email protected]
Phone: +61 (0)3 6226 7745
The laboratory of molecular neurobiology comprises three complementary research teams that
work together to investigate the mechanisms that regulate normal brain development and
ageing, and understand how dysregulation of these processes can lead to neurological
impairment and / or degeneration.
PhD and honours projects that can be undertaken within the group are detailed below.
Research Interests:
New neurons and glial cells are continuously added to the central nervous system. These new
cells represent an amazing resource for central nervous system repair. Dr Young's research
team investigates various aspects of neural stem and progenitor cell biology, and aims to
understand their response to injury / disease and their ability to regenerate the damaged
nervous system. They are particularly interested in overcoming the demyelination and
oligodendrocyte damage detected in Multiple Sclerosis, Alzheimer's Disease and
Schizophrenia.
Student Background:
Students must have a keen interest in understanding how the nervous system works. A science
degree that involved studying Neuroscience is essential, and Molecular Biology,
Biochemistry or Genetics is also desirable.
Project 1: Can the brain’s endogenous progenitor / stem cells make new cells for brain
repair?
A significant component of Alzheimer’s Disease (AD) pathology results from the
dysregulation of a protein called amyloid. The level of soluble amyloid has been
demonstrated to correlate well with the extent of memory deficits experienced by AD
patients, and there is growing evidence that amyloid can be cytotoxic and lead to neural
degeneration. While most research into AD investigates the consequences of amyloid toxicity
on neurons, recent experimental evidence indicates that other cells maybe severely affected
and contribute to the progression of the disease. Neural stem cells and oligodendrocyte
progenitor cells (OPCs) are two immature cell populations that remain in the adult brain well
after development is complete, and continue to divide and make new neurons and
oligodendrocytes throughout life.
We will use cre-lox transgenic technology to fluorescently label and trace each cell
population, and compare their behaviour in the brains of normal mice and mice that have been
genetically modified to develop AD. This project aims to determine whether neural stem cells
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An institute of the University of Tasmania
or OPCs are damaged by the toxic accumulation of amyloid in AD, and whether this
influences their ability to make new cells for the adult brain.
Project 2: How do oligodendroglial cells replenish their ER calcium stores?
Oligodendrocyte progenitor cells (OPCs) are the largest proliferating cell population in the
adult brain, comprising ~5% of all brain cells. The function of these cells is to generate new
oligodendrocytes in the normal brain, and contribute to remyelination in response to a
demyelinating disease such as multiple sclerosis. It was recently discovered that neurons
form synapses onto OPCs, and that neuronal activity can influence OPC behaviour. But how
this occurs is largely unknown. As neuronal activity has been shown to evoke a calcium
signal within OPCs, we hypothesise that calcium signalling directs OPC behaviour, and will
be reliant on calcium release from the endoplasmic reticulum (ER).
We will examine OPCs and oligodendrocytes in vitro and in vivo to determine which
components of the calcium-induced calcium release pathway are active in each cell type, their
sub-cellular localisation, and whether their manipulation can prevent or promote
oligodendrocyte differentiation. This project aims to determine the mechanism by which
calcium signalling is regulated within OPCs.
Project 3: Do primary cilia play a central role in regulating neural progenitor cell
behaviour and function in the adult brain?
Primary cilia are specialized cellular organelles that are functionally important for neural stem
cell maintenance in the central nervous system, and schwann cell maturation and myelination
in the peripheral nervous system. However a role for primary cilia in regulating
oligodendrocyte progenitor cell (OPC) function in the adult central nervous system has not
been investigated. OPCs are the largest proliferating cell population in the adult brain,
comprising ~5% of all brain cells. The function of these cells is to generate new
oligodendrocytes for the normal CNS and to achieve remyelination in response to a
demyelinating injury in diseases such as multiple sclerosis. OPCs reportedly undergo both
symmetric and asymmetric cell divisions, and their rate of division varies greatly between
brain regions, however we do not sufficiently understand how these processes are regulated.
This project aims to investigate the role of primary cilia in regulating OPC behaviour. We
will examine OPCs and oligodendrocytes in vitro and in vivo to identify the state of primary
cilia assembly in each cell type, and characterise changes that occur as part of the
differentiation process. We will also determine which key signalling proteins localise to this
region of the OPC.
Project 4: New oligodendrocytes are added to the adult central nervous system – what is
their function?
Oligodendrocyte Progenitor Cells (OPCs) are the largest proliferating cell population in the
adult brain, comprising ~5% of all brain cells. Throughout life OPCs generate new
oligodendrocytes which mature and ensheath multiple axons, producing myelin internodes.
Axon myelination significantly increases action potential conduction speeds. However it is
unclear whether the addition of new myelin in adulthood represents a novel form of central
nervous system plasticity, or is a method of central nervous system maintenance.
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An institute of the University of Tasmania
We will use cre-lox transgenic technology to fluorescently label the myelin of adult-born
oligodendrocytes, allowing us to characterise how new myelin internodes inter-collate with
developmentally formed myelin internodes, along individual axons.
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An institute of the University of Tasmania