Research Opportunities

The Woolcock Institute of Medical Research is offering a number of Honours and Graduate research projects. The research areas offered are listed below. Further details about the individual projects can be obtained from the project leaders listed.

Allergen Group

Dr Euan Tovey

Cat allergy – exposure, avoidance and symptoms
The relationship between exposure to the allergens produced by domestic cats and clinical outcomes such as allergic sensitisation and asthma symptoms is both complex and unclear. There is currently little quantitative information on the actual patterns of daily exposure to cat allergens of both cat owners and non-cat owners, or why very high exposure to cat allergens may be protective for outcomes in some people and is a risk factor in others, or how exposure declines over time when a cat is removed from a house or what the pattern is of clinical outcomes in cat-sensitive people when exposure is greatly reduced. We have excellent methods for measuring personal exposure to cat allergens. The aim of this project is to apply these methods in a series of studies of cat allergen exposure in groups of cat-allergic people with asthma, living with or without cats or moving between exposure situations, created either by intervention or by moving locations.

The nature of exposure to fungal aeroallergens
This year we published a landmark paper that will discreetly change the way exposure to fungal allergens is understood in future. We used methods, developed in-house, to show two things about fungal exposure: that the carriers of a significant minority of fungal allergens are the fine threads of fungal hyphae and not the larger fruiting conidia (spores) that have previously been assumed to be the sources of exposure. Secondly, that a sizable minority of fungal allergen exposure occurs from fungal genera that have not previously been identified as allergen sources. The aim of this project is to apply our methods in different and selected indoor and outdoor exposure situations, and relate this exposure to the clinical symptoms of different fungal-allergic people.

The nature and reduction of domestic aeroallergen exposure
Being allergic to domestic allergens (mite, cat, dog, cockroach etc) is strongly associated with much, but not all asthma, particularly in children. The understanding of the role of allergen exposure to chronic and acute asthma symptoms and airways hyper-responsiveness is limited, partly by the current paucity of quantitative information on the nature and periodicity of that exposure. Despite global guidelines strongly advocating that allergic patients reduce exposure to the allergens that they are allergic to, the mechanics of effectively performing this in normal domestic situations are elusive and weakly founded. Indeed many of the basics, such a the role of bedding, whether carpets are good or bad, the usefulness of vacuum cleaning or air filters on exposure are all controversial and under researched. Technically, we are superbly positioned to contribute to this important area of public health. This project will aim to build a framework describing normal domestic allergen exposure and quantify the efficiency of the some of the more common ways of reducing aeroallergen exposure.

Masks and filters for viruses
We have a new-found interest in masks and filters used for protection against respiratory viruses such as influenza and rhinovirus. There are numerous issues that require attention, including characterizing the generation of aerosols by different respiratory events (cough, sneeze, talk etc), factors that influence the dispersion of these airborne particles in the environment, and the extent that different masks and filters provide protection, both from the exhalation of these by an infected person and also the inhalation of them by a person at risk of infection. Other forms of transmission are also of interest, such as via contact with dried mucous on surfaces (fomites). We are developing collection techniques in these areas and collaborating with others who possess sensitive PCR assays.

Clinical Mechanisms

Dr Greg King, Dr Cheryl Salome

The Asthma Mechanisms Group of the Woolcock Institute of Medical Research has research projects in the area of lung physiology.

The Woolcock Institute of Medical Research is based on the campus at Royal Prince Alfred Hospital, but we have collaborative links with Royal North Shore and Liverpool Hospitals, and with groups at the John Hunter Hospital in Newcastle, all of whom provide a range of skills and experience to draw on. The WIMR is also the senior partner in the CRC for Asthma, which offers opportunities to have contact with our major industry partners.

The Asthma mechanisms group is primarily interested in the abnormalities of airway function associated with asthma. Our studies involve physiological and clinical evaluations of patients with asthma and chronic obstructive pulmonary disease, and healthy controls. We have a wide range of physiological and imaging techniques established either at the RPAH campus or at RNS.

Current research areas:

• Role of dynamic changes in airway caliber as an indicator of altered airway smooth muscle function in asthma.
• The use of imaging techniques, such as high resolution CT or SPECT scanning, to measure variation in airway narrowing through the bronchial tree.
• New physiological methods and computational models to describe small airway function in respiratory disease.
• Non-invasive methods for measuring airway inflammation in asthma
• Improved treatment outcomes in chronic obstructive pulmonary disease (COPD).

These projects provide opportunities for PhD, Masters and Honours students with an interest in lung physiology, airway imaging and clinical studies. Through our collaborations with other groups, there is also some scope for extending these studies into more basic research areas. We currently have 4 PhD students in the asthma mechanisms group, so there is a very supportive environment with lots of opportunity to share experience and knowledge.

Epidemiology Group

Associate Professor Guy Marks, Dr Brett Toelle, Dr Wei Xuan

The Epidemiology Group of the Woolcock Institute of Medical Research has research projects in the area of asthma, tuberculosis and planning a project in Chronic Obstructive Pulmonary Disease. The senior members of the group are Assoc Professor Guy Marks (Respiratory Physician/Epidemiologist), Dr Brett Toelle (Research Fellow) and Dr Wei Xuan (Biostatistician).

Childhood asthma prevention study
Between 1997 and 2005 we conducted a randomised controlled trial of two interventions, house dust mite avoidance and dietary fish oil supplementation, in children at high risk of asthma because of a family history of asthma. The children were recruited at birth and randomised to active or control interventions, which were implemented throughout the first five years of life. Throughout this time participants were closely monitored with frequent measurements of a range of environmental risk factors as well as assessments of allergic and respiratory disease outcomes. Data on a number of biological markers has also been collected.

During the period 2006 to 2008 we will be conducting a further detailed assessment of clinical outcomes in this cohort of 600 children. Subjects will be aged eight years at the time of this assessment. The objectives are to assess long term outcomes of the trial interventions and to evaluate the impact of a range of environmental exposures on the risk of asthma during childhood.

The project is funded by NHMRC and presents an excellent opportunity for a PhD student interest in respiratory health, paediatrics, allergy -immunology and/or epidemiology.

20-year longitudinal asthma and allergy study
The Epidemiology Group has a large data set collected from a well-characterised cohort of children who in 1982 were aged 8 – 10 years. Every two years between 1982 and 1992 then every 5 years until 2002 these individuals have provided detailed questionnaire information and most have undertaken clinical investigations. The last follow up was conducted in 2002 when members of the cohort were adults aged 28 – 31 years.

Project 1: Analysis of the gender difference in asthma
Boys have more atopy and more asthma but after puberty, women have more asthma. What is happening? What are the characteristics of the boys who move into remission and the characteristics of the girls who develop asthma? Are females always less atopic than males no matter what age? Over the course of this 20-year study what is the difference in the relationship between atopy and asthma at different ages and between the sexes?

Project 2: How is airway resistance measured in adulthood different between those who did and didn't have asthma as a child?
Members of the cohort can be divided into classifications of a) Normal - NEVER had asthma b) PAST asthma c) CURRENT asthma. There are multiple data points for each member of the cohort so it is possible to work up fairly comprehensive past and current definitions. For example NEVER by taking into account all visits, CURRENT by using the last two visits and PAST by taking into account the first two visits.

Project 3: Analysis of the natural history of asthma control
We have suggested and published classifications of "Asthma Symptoms" and "Troublesome Asthma". How does the prevalence of these classifications at different ages over the course of this 20-year study? What changes when subjects drop in and out of these classifications? What are the treatment approaches, morbidity and symptoms associated with these classifications?

Project 4: Prevalence of asthma and allergy in 28-30 year old adults
The study has a very respectable response rate 84%. Although the majority of cohort members still reside in Newcastle the cohort are scattered geographically. But they do represent a particular population of children born in Belmont between 1976 and 1978 at the start of the increase in prevalence recorded worldwide. We have clinical information on 45% of the cohort. But by looking at the relationship between questionnaire responses and clinical measures in those 45% who completed both we can adjust the prevalence figures

Cell Biology & Molecular Medicine

Professor Judy Black

Abnormal airway smooth muscle cells may be the key to asthma
We use cellular and molecular techniques to identify mechanisms underlying the abnormal properties of airway smooth muscle cells derived from asthmatic volunteers- a resource which is unique world-wide.

Cystic Fibrosis

Associate Professor Peter Bye

The Cystic Fibrosis has a large and active research group. There are broad areas of current research activity, because our group believes it is important to tailor projects to the interest of individual research students and involve them in every stage of the research project. This includes formulating the scientific hypothesis and designing the studies/experiments to test this hypothesis. Our experienced research personnel will assist students at every step of this process. The main areas of research interest with current projects include:

• Measurement of mucociliary clearance
• Sleep disordered breathing in CF patients
• Physiological studies of gas exchange
• Microbiology
• Effect of exercise programs on morbidity and mortality in people with CF
• Clinical Trials

In additions, the Microbial Molecular Epidemiology and Antibiotic Resistance Surveillance group offers the following projects:

• Epidemiology of multi-drug resistant Pseudomonas aeruginosa in Cystic Fibrosis patients
• Markers of antibiotic resistance and their transmission among bacterial pathogens of Cystic Fibrosis patients
• Molecular studies to determine virulence markers in epidemic clones of Pseudomonas aeruginosa
• Genetic characterisation and evolution of Multi-resistant Staph. Aureus (MRSA)

Sleep & Circadian Research

Professor Ron Grunstein 

The Sleep & Circadian Research Group at the Woolcock Institute of Medical Research is a multidisciplinary group of researchers investigating a wide range of research related to sleep, sleep loss, sleep disorders and circadian rhythms. We have a number of different research interests focused on these areas, including examining the links between sleep disordered breathing and development of metabolic syndrome; and the consequences of circadian disruption and sleep deprivation in individuals with respiratory disorders.

Project 1: Effect of SDB and its treatment on post-prandial hyperlipidemia.
Data from various studies, including our own work, demonstrates that Metabolic Syndrome (Msynd) and Sleep Disordered Breathing (SDB) are closely linked. Features common to both include insulin resistance, increased central adiposity, hyperlipidemia and hypertension. While central fat increases produce SDB, it has not been clearly demonstrated that SDB causes central adiposity or any of the other features of Msynd.

This study aims to establish whether SDB has a pathogenic role in the development of hyperlipidemia. Subjects with Metabolic Syndrome are characterised by increased postprandial lipidemia, a risk factor for atherosclerosis. There is no data on the role of SDB in the promotion of postprandial hyperlipidemia, hence one of the key aims of this study is to identify the presence of postprandial hyperlipidemia in SDB, relate it to SDB severity in humans and measure its reversibility with CPAP. Moreover, the hypoxia and other metabolic effects of SDB may also exacerbate the detrimental effect of dyslipidaemia on endothelial function. As such, this study will also investigate the impact of intermittent hypoxia on PPL in animal models.

Contact
Craig Phillips
T 9114 0448
E cphillip@mail.usyd.edu.au

Project 2: Effects of circadian disruption on neurobehavioural and physiological variables in respiratory disorders
A number of studies have demonstrated significant effects of acute circadian disruption on neurobehavioural capabilities, sleep physiology and other physiological variables in healthy subjects. Little work has been done, however, examining the effects of acute circadian disruption on patients with respiratory disorders, such as sleep apnoea and asthma.

This study aims to examine the effects of simulated jet lag on a number of physiological (sleep, respiratory, temperature) and neurobehavioural (neurocognitive function, subjective assessments) variables in healthy subjects and patients with sleep apnoea or asthma. This study involves maintaining subjects in a controlled time isolation laboratory for approximately one week, with continuous monitoring and repeated assessments of physiological and neurobehavioural function.

Contact
Craig Phillips
T 9114 0448
E cphillip@mail.usyd.edu.au