Prof Caroline (Lindy) Rae

Early detection of Parkinson’s disease

This project aims to better identify those at higher risk of subsequently developing Parkinson’s disease with the aim of being about to test and validate potential preventative measures. We aim to identify people at risk while they are still healthy before irreversible major cell loss has occurred.

Collaborators: Kay Double, USyd; Gabrielle Todd, UNiSA, Karl Aoun (Usyd)

 

A unified model of amino acid homeostasis

This Australian Research Council funded project (DP180101702) aims to understand the functions that amino acids play in brain, in particular in protein biosynthesis and energy generation. We are using a combination of genetic and pharmacological manipulation in conjunction with isotope labelling and NMR spectroscopy to help build our model.

 

Collaborators: Stefan Bröer, ANU, Brian Billups, ANU, Abhijit Das NeuRA

Binge drinking and the adolescent brain

This study is examining the neurobiological impact of binge alcohol consumption in 16-17 yo adolescents using magnetic resonance imaging and spectroscopy along with cognitive and behavioural measures.

Collaborators: Lucette Cysique, NeuRA; Maree Teesson, NDARC Louise Mewton NDARC

 

Lees, B., Mewton, L., Stapinski, L, Squeglia, L. M., Rae, C. & Teesson, M. (2018) Binge drinking in young people: Protocol for a systematic review of neuropsychological, neurophysiological and neuroimaging studies. BMJ Open 8 (7) e023629.

Brain network discovery in medical research

In collaboration with colleagues in Electrical Engineering at UNSW we are developing and applying new methods for identifying and comparing brain functional and structural networks.

Main Collaborators: Victor Solo (UNSW); Ben Cassidy (NeuRA); Michael Green (NeuRA)

 

Cassidy, B., Rae, C. & Solo, V. (2015) Brain activity: connectivity, sparsity and mutual information. IEEE Transactions on Medical Imaging 34, 846-860.

Cassidy. B., Bowman, D., Rae, C. & Solo, V. (2018) On the reliability of individual brain activity networks. IEEE Transactions in Medical Imaging 37, 649-662.

New Methods for analysis and visualisation of metabolic data

Systems biochemistry requires the understanding and manipulation of large data sets. Here, we are applying network analysis methods from other disciplines to metabolic datasets. In collaboration with the Expanded Perception and Interaction Centre (EPICentre) at UNSW and the Australian Metabolic Phenotyping Centre based in WA, we are developing data visualisation tools for these datasets that work across a variety of 2D, and immersive platforms.

 

Main Collaborators: Tomasz Bednarz EPICentre; Jeremy Nicholson, Murdoch University

Regulation of brain energy metabolism by NAD and sirtuins

All cells require a constant supply of energy to survive, however the active and dynamic environment within the brain imposes not only a high basal energy requirement, but also vastly fluctuating energy demands across the course of a normal day. Fundamental to understanding brain energy metabolism is the lynchpin molecule, nicotinamide adenine dinucleotide (NAD). Despite its central importance to brain metabolism, we still do not know how the fundamental processes of NAD synthesis, recycling and catabolism are regulated in brain.  Through use of highly innovative and novel strategies combining new molecular tools and flagship infrastructure, we are selectively dissecting the synthesis and roles of NAD across the 3 major classes of neural cells – neurons, astrocytes, oligodendrocytes. The results of this project will generate a systems biology platform to underpin manipulations of NAD homeostasis as well as to understand the relationship between brain NAD levels and mitochondrial function.

Main Collaborators: Gary Housley (SOMS), Matthias Klugmann (SOMS), Ben Rowlands (NeuRA)

Rowlands, B., Klugmann, M & Rae, C.D. (2017) Acetate metabolism does not reflect astrocytic activity, contributes directly to GABA synthesis, and is increased by silent information regulator 1 activation. The Journal of Neurochemistry  140, 903-918.

Determining new targets and approaches for treating sleep apnoea

Sleep apnoea results in cognitive dysfunction, excessive sleepiness, doubling of workplace accidents  and more than 2-fold increased motor vehicle crash risk presenting a huge health care burden in Australia and internationally. The disorder is also associated with increased risk of stroke, heart disease and possibly dementia. It is a complex disorder with multiple impacts including hypoxia, sleep deprivation, metabolic syndrome and cardiovascular risk factors.

This project aims to unravel the impact of OSA on the brain and to determine whether deleterious effects can be reversed or slowed by treatment options.

 

Main collaborators: Andrew Vakulin, Flinders; Ron Grunstein, Woolcock Institute, Angela D’Rozario, Woolcock Institute, Delwyn Bartlett, Woolcock Institute; Lynne Bilston, NeuRA, Michael Green, NeuRA

Miller, C.B., Rae, C.D. Green, M., Yee, B.J., Kyle, S.D., Gordon, C.J., Marshall, N.S., Espie, C.A., Grunstein, R.R. & Bartlett, D.J. (2017) An objective short-sleep insomnia disorder subtype is associated with reduced brain metabolites in vivo: a preliminary magnetic resonance spectroscopy assessment. Sleep 40, zsx148

D’Rosario, A., Bartlet, D., Wong, K.H., Sach, T, Yang, Q., Grunstein, R.R. & Rae, C.D. (2018) Brain bioenergetics during resting wakefulness are related to neurobehavioural deficits in severe obstructive sleep apnea. Sleep 41(8) zsy117.

Determining new targets and approaches for treating sleep apnoea

We are running a range of projects to determine how existing treatments for sleep apnoea work so that we can optimise therapy and improve treatment success.

Regulation of brain energy metabolism by NAD and sirtuins

This project is investigating control of metabolism by sirtuins and by NAD+ availability using an innovative, pharmacogenetic approach to metabolism research and “world-first” cell-specific introduction of enzymes into tissue in vivo. It will deliver an integrated picture of how SIRTs 1-3 and NAD+ interact with metabolism, crucial for development of next generation treatments based on this system. Finally, in preclinical translation, we will test the therapeutic effects of manipulating this system to combat decreased NAD+ availability and SIRT activity within the aging brain.

New methods for analysis and visualisation of metabolic data

We are developing new approaches that allow representation of metabolomic data as a network, while still retaining some elements of data reduction in order to remove the immense complexity associated with analysis.

Brain network discovery in medical research

Scientists discovered some time ago that they could use magnetic resonance imaging (MRI) to map brain activity when a person was repetitively performing a task, like looking at flashing lights or doing serial maths calculations. More recently, they found that these MRI signals could also provide useful information when the scanned subject was not doing anything. They called these signals “resting state” signals. Our new analysis approach for resting state data uniquely provides repeatable, reliable results from single scanning sessions. We are developing methods for network comparison and are applying our new approaches across a targeted range of patient data.

Binge drinking and the adolescent brain

This study is examining effects of binge alcohol consumption in 16-17 year olds using questionnaires, magnetic resonance imaging and cognitive testing. It aims to determine whether binge consumption of alcohol is impacting adolescent brain and cognitive development.

Novel brain biomarkers of neurobehavioural dysfunction in obstructive sleep apnoea

This study aims to investigate the relationship between brain biomarkers measured at baseline, with neurobehavioural dysfunction during a subsequent extended wakefulness “load” that will uncover the individual variation in neurobehavioral dysfunction in patients with obstructive sleep apnoea.