Research projects

Health services, health systems, health informatics

The Australian Institute of Health Innovation is at the forefront of healthcare system research and the implementation of real improvements to health services in Australia and around the world. The Institute comprises the Centre for Healthcare Resilience and Implementation Science (CHRIS), the Centre for Health Informatics (CHI), and the Centre for Health Systems and Safety Research (CHSSR). Projects are often conducted collaboratively across the Centres, taking advantage of specialisations in each area.

AIHI welcomes applications for Higher Degree Research from students of diverse backgrounds, including psychology, anthropology, medical science, health and allied health professions, and computer science.

We particularly welcome practicing health professionals with an interest in research to contact us.

See our current scholarship opportunities and specialist areas of research: Study at AIHI

Neurobiology of vital systems

The Neurobiology of Vital Systems group is recruiting Masters and PhD students to work on
exciting projects in the field of autonomic neuroscience.How to apply These projects continue a program of research that investigates the architecture and functional organisation of the neural systems that keep us alive.

Key research topics in this field are:

THEME 1: Central mechanisms that generate respiratory-sinus arrhythmia

It has long been known that heart rate waxes and wanes with the respiratory cycle, a phenomenon known as respiratory sinus arrhythmia. Similar respiratory-entrained fluctuations are also present in the activity of the sympathetic nerves that innervate blood vessels and in blood pressure itself. The mechanisms responsible for these interactions are unclear, but data from human and animal studies show a link between the strength of these interactions and cardiovascular risk, which remains the main determinant of life expectancy worldwide, with reduced respiratory sinus arrhythmia and increasing respiratory-sympathetic coupling acting to increase morbidity.

Our group is recruiting students to work on two aspects of this theme that will focus on the fundamental organisation of these circuits in rodents.

Project 1: How are the neurons that control heart rate connected to those that control breathing?

The first project will use state-of-the-art genetically restricted viral tracers to map sources of monosynaptic input to cardiac vagal motoneurons, the part of the parasympathetic nervous system that ultimately controls heart rate. Building on viral tracing, imaging, mapping and analysis technologies established in our laboratory, this project will provide a definitive and comprehensive map of the brain systems that control heart rate.

Recommend reading:

• Saleeba C, Dempsey B, Le S, Goodchild A, McMullan S (2019) A Student's Guide to Neural Circuit Tracing. Frontiers in neuroscience 13:897. https://doi.org/10.3389/fnins.2019.00897
• Menuet C, Le S, Dempsey B, Connelly AA, Kamar JL, Jancovski N, Bassi JK, Walters K, Simms AE, Hammond A, Fong AY, Goodchild AK, McMullan S, Allen AM (2017) Excessive Respiratory Modulation of Blood Pressure Triggers Hypertension. Cell Metab 25:739-748. https://doi.org/10.1016/j.cmet.2017.01.019
• Dempsey B, Le S, Turner A, Bokiniec P, Ramadas R, Bjaalie JG, Menuet C, Neve R, Allen AM, Goodchild AK, McMullan S (2017) Mapping and Analysis of the Connectome of Sympathetic Premotor Neurons in the Rostral Ventrolateral Medulla of the Rat Using a Volumetric Brain Atlas. Front Neural Circuits 11:9. https://doi.org/10.3389/fncir.2017.00009

Project 2: What are the functional properties of neurons that co-ordinate respiratory-sympathetic coupling?

The second project builds upon recent work from our lab that identifies the intermediate reticular nucleus (IRt) as a critical node for the transmission of respiratory drive to sympathetic premotor neurons that control blood pressure. The objective of the current project will be to functionally identify so-called post-inspiratory neurons in the IRt and determine the mechanisms that determine their excitability. This project will use in vivo electrophysiological techniques, supported by machine learning analytical approaches, to assess the functional properties of neurons within this nucleus.

Recommend reading:

• Dempsey B, Le S, Turner A, Bokiniec P, Ramadas R, Bjaalie JG, Menuet C, Neve R, Allen AM, Goodchild AK, McMullan S (2017) Mapping and Analysis of the Connectome of Sympathetic Premotor Neurons in the Rostral Ventrolateral Medulla of the Rat Using a Volumetric Brain Atlas. Front Neural Circuits 11:9. https://doi.org/10.3389/fncir.2017.00009
• Anderson TM, Garcia AJ, 3rd, Baertsch NA, Pollak J, Bloom JC, Wei AD, Rai KG, Ramirez JM (2016) A novel excitatory network for the control of breathing. Nature 536:76-80. https://www.nature.com/articles/nature18944
• Toor R, Sun QJ, Kumar NN, Le S, Hildreth CM, Phillips JK, McMullan S (2019) Neurons in the intermediate reticular nucleus coordinate post-inspiratory activity, swallowing, and respiratory-sympathetic coupling in the rat. J Neurosci [In Press]

THEME 2: Activation of cardiovascular circuits by environmental stimuli

We all know that cardiovascular and respiratory changes are components of the physiological responses to threat – when surprised, we gasp, we suffer surges in blood pressure, and our heart rates soar. These responses help us to prepare for whatever the environment throws at us, but hyperactivity of these circuits is characteristic of psychological conditions such as post-traumatic stress disorder (PTSD) and may be responsible for elevating the cardiovascular risk associated with stress and anxiety disorders.

In recent years we have unravelled a previously undiscovered neural circuit that links sensory integration centres in the brainstem with cardiovascular control nuclei. Our (thusfar unpublished) observations point to a critical role for neurons in the rostral ventromedial medulla in the elaboration of cardiovascular responses to acute visual stimuli. We think that this projection is responsible for generating cardiovascular responses to diverse stimuli, which may be appetitive or aversive, and which serve to support physiological responses to a range of environmental circumstances.

This project will use a combination of optogenetics, behavioural and physiological techniques to examine the role played by this pathway in the generation of cardiovascular, respiratory and motor responses to external stimuli.

Recommend reading:

• Muller-Ribeiro FC, Dampney RA, McMullan S, Fontes MA, Goodchild AK (2014) Disinhibition of the midbrain colliculi unmasks coordinated autonomic, respiratory, and somatomotor responses to auditory and visual stimuli. Am J Physiol Regul Integr Comp Physiol 307:R1025-1035.
• Muller-Ribeiro FC, Goodchild AK, McMullan S, Fontes MA, Dampney RA (2016) Coordinated autonomic and respiratory responses evoked by alerting stimuli: Role of the midbrain colliculi. Respir Physiol Neurobiol 226:87-93.
• Furlong TM, McDowall LM, Horiuchi J, Polson JW, Dampney RA (2014) The effect of air puff stress on c-Fos expression in rat hypothalamus and brainstem: central circuitry mediating sympathoexcitation and baroreflex resetting. Eur J Neurosci 39:1429-1438.

How to apply

Interested candidates should contact Associate Professor Simon McMullan (simon.mcmullan@mq.edu.au) to discuss these opportunities in detail.

Neuroinflammation group

THEME 1: The role of BMAA in neurodegenerative diseases

Project 1a: Elucidating the subcellular effects of BMAA on somatic and axonal degeneration

The algal neurotoxin β-Methylamino-L-alanine (BMAA) is associated with motor neuron disease (MND) and has been shown to enter brain cells. Its neurotoxic properties are well known, however, its effects on subcellular compartments of neurons are unclear. Using microfluidic chambers, we have previously shown that somatic exposure to BMAA causes more degeneration to the axons of neurons than to their soma, suggesting that BMAA might affect the peripheral nervous system more strongly. We aim to determine the effect of axonal exposure of low concentrations BMAA on axonal degeneration and somatic death.

Expected outcomes:

1. Determine if axonal BMAA exposure results in more axonal degeneration.
2. Assess the retrograde transmission of BMAA within and between cells.

Key techniques: Cell culture, immunocytochemistry, microscopy

Project 1b: Investigating transmissibility of the neurotoxin BMAA

The algal neurotoxin BMAA has been shown to enter brain cells, be transported within the cell, and transmitted between neural cells. We aim to show the spread of BMAA in neurons by synthesizing fluorescently labelled BMAA to allow real-time tracking of BMAA.

Tracking the fluorescently labelled BMAA in vitro will allow us to build hypotheses and lay the groundwork to develop therapeutic methods to disrupt BMAA uptake and transmission to block or slow disease. It will also allow us to test our overarching hypothesis for BMAA entering the central nervous system (CNS) and spreading in a retrograde manner.

Expected outcomes:

1. Synthesize novel fluorescently labelled BMAA.
2. Observe the uptake of BMAA into neuronal cells, and transport within and between neuronal cells.
3. Gather preliminary evidence of BMAA uptake, transport, and transmission in neurons.

Key techniques: Cell culture, microscopy

Project 1c: Role of BMAA in MND-associated protein dysfunction

The algal neurotoxin BMAA has been shown to enter brain cells and is associated with MND. There is preliminary evidence that BMAA is bound in proteins and may cause protein misfolding and aberrations. This project will elucidate the protein binding and misfolding properties of BMAA in MND proteins through the observation of BMAA integration or association with MND-related proteins, in cell cultures and mouse brain tissues (samples ready for analysis). We will analyse primary human neuronal cells exposed to BMAA for protein changes, as well as observe MND pathologies in these cells to establish whether BMAA contributed to the development of MND.

Expected outcomes:

1. Determine if BMAA is integrated or associated with MND related proteins.
2. Establish the role of BMAA in causing MND-like pathologies in cell cultures and mouse brain tissue sections.

Key techniques: Cell culture, microscopy, immunostaining, protein dysfunction, proteostasis

How to apply

Candidates interested in this thematic area or these projects should contact gilles.guillemin@mq.edu.au or vanessa.tan@mq.edu.au to discuss these opportunities in detail.

THEME 2: Biomarkers for MND

There is a pressing need for biomarkers in MND, not only to independently determine the progression of the disease, but also to delineate the different subtypes of the disease and provide a prognosis. Such biomarkers would be informative to the patients and their families, and would hold great clinical significance for the scientific and clinical research community in developing better research by enabling targeted research and treatments for the various disease subtypes in the clinical spectrum. More than 90 neuroinflammation and disease associated biomarkers on longitudinal patient and control samples are being assessed.

Expected outcomes:

1. Longitudinal information on changes in neuroinflammation within patients with MND.
2. Development of biomarkers that can be used to confirm diagnosis, and as progression and prognostic biomarkers.

Key techniques: Elisa, data management, biostatistical analys

How to apply

Candidates interested in this thematic area or these projects should contact gilles.guillemin@mq.edu.au or vanessa.tan@mq.edu.au to discuss these opportunities in detail.