MND research grants 2021

PROJECTS COMMENCING IN 2021

BETTY AND JOHN LAIDLAW MND RESEARCH PRIZE 2021
A/Prof Yazi Ke Macquarie University, NSW	Betty and John Laidlaw MND Research Prize awarded to an outstanding mid-career researcher	Novel therapeutic strategies targeting TDP-43 in Motor Neuron Disease

POSTDOCTORAL FELLOWSHIPS (2021 – 2023)
Dr Thomas Shaw University of Queensland, QLD	Bill Gole MND Postdoctoral Fellowship 2021 – 2023	Ultra-High Field MRI of Spinal Cord Tissue in Motor Neurone Diseases
Dr Emily McCann Macquarie University, NSW	Beryl Bayley MND Postdoctoral Fellowship 2021 – 2023	Investigating the role of complex genomic variation in MND
Dr Nicholas Geraghty University of Wollongong, NSW	Marisa Aguis MND Postdoctoral Fellowship 2021 – 2023	High-throughput flow cytometry drug screen to discover new treatments for MND

 

INNOVATOR GRANTS 2021
Dr Shyuan Ngo University of Queensland, QLD	Charcot Award, funded by the NTI MND Research Grant awarded to the highest ranking innovator grant application	MND in space and time: deciphering the spatio-temporal landscape of cell-autonomous and non-cell-autonomous drivers of motor neuron death in MND
Dr Victor Anggono University of Queensland, QLD	Judy Mitchell MND Research Grant	Molecular mechanisms underlying the cytoplasmic aggregation of the RNA binding protein, SFPQ, in ALS
Prof David Berlowitz University of Melbourne, VIC	Mavis Gallienne and Graham Lang MND Victoria Research Grant	REPAIR MND: REduced PAtient – ventilator asynchrony with Artificial Intelligence assisted Respiration in MND
Prof Ian Blair Macquarie University, NSW	Peter Stearne Familial MND Research Grant	Genome-wide detection of short tandem repeats that are expanded in ALS
Dr Christopher Bye The Florey Institute of Neuroscience and Mental Health, VIC	Robert Turnbull MND Research Grant	Next generation pre-clinical modelling for MND
Dr Mouna Haidar The Florey Institute of Neuroscience and Mental Health, VIC	Jack and Joan Thompson MND Research Grant	Will reducing abnormal cortical activity in MND have a therapeutic effect?
Dr Robert Henderson​ University of Queensland, QLD	Col Bambrick MND Research Grant	A Novel PET Imaging Marker of Astrocytes and Glutamate Reuptake in Brain and Spinal Cord in ALS
Dr Colin Mahoney University of Sydney, NSW	Dr Angela Worthington MND Research Grant	Establishing the role of high definition-density EEG in the diagnosis and monitoring of MND
Prof Pamela McCombe  University of Queensland, QLD	Run MND NSW Research Grant	Revisiting excitotoxicity in ALS: how does this occur?
Dr David McKenzie University of Sydney, NSW	Dr Paul Brock MND NSW Research Grant	Development of an amperometric biosensor for the detection of TARDNA binding protein 43 (TDP-43) in MND
Dr Nirma Perera The Florey Institute of Neuroscience and Mental Health, VIC	Jenny Simko MND Research Grant	Autophagy in Neuroglia: a hidden player in abnormal MND proteostasis
Dr Frederik Steyn University of Queensland, QLD	MonSTaR MND Research Grant	Targeting NAT1 to improve metabolism and slow disease progression in MND
A/Prof Bradley Turner The Florey Institute of Neuroscience and Mental Health, VIC	Superball XIII MND Research Grant	Defining upper motor neuron markers using translational RNA profiling
Dr Adam Walker University of Queensland, QLD	Fat Rabbit MND Research Grant	Defining the involvement of ubiquilin-2 in MND

 

MNDRA Linda Rynalski Bridge Funding Grants 2021
Professor Julie Atkin Macquarie University, NSW	Novel mechanisms of neurodegeneration induced by dysfunctional actin dynamics in MND
Dr Richard Gordon University of Queensland, QLD	Targeting inflammasome-driven neuropathology and motor neuron death in MND using a clinically approved cancer drug
Dr Albert Lee Macquarie University, NSW	Clearance of TDP-43 by PROteolysis TArgeting Chimera (PROTAC) dual targeting to treat ALS
Dr Fiona McKay University of Sydney, NSW	Natural Killer cells in amyotrophic lateral sclerosis
Dr Marco Morsch Macquarie University, NSW	The unexplored posttranslational modification (SUMOylation) of TDP-43 affects aggregate formation and localisation
A/Prof Mary-Louise Rodgers Flinders University, SA	Urinary Neopterin as a candidate biomarker that can be used to test disease progress in clinical trials for Motor Neurone Disease
Dr Kara Vine University of Wollongong, NSW	Non-invasive drug delivery across the blood brain barrier: Improving the bioavailability of drugs for MND
Dr Trent Woodruff University of Queensland, QLD	Transcriptomic and Functional Evaluation of Immune-Activated Monocytes in MND

 

MULTI-YEAR GRANTS FROM PREVIOUS YEARS CONTINUING IN 2021

BETTY LAIDLAW MND RESEARCH PRZIE (2020– 2021)
Dr Shyuan Ngo  University of Queensland, QLD	Betty Laidlaw MND Research Prize awarded to an outstanding mid-career researcher	From the nucleus to the powerhouse: investigating how TDP-43- mitochondrial interactions wreak havoc in MND

 

POSTDOCTORAL FELLOWSHIPS (2020– 2022)
Dr Luke McAlary University of Wollongong, NSW	Bill Gole MND Postdoctoral Fellowship 2020– 2022	Targeting Prion-Like Strains of TDP-43
Dr Mehdi van den Bos Westmead Hospital, NSW	Beryl Bayley MND Postdoctoral Fellowship 2020 – 2022	Deep learning as a tool to advance the diagnosis and pathophysiological understanding of ALS

 

POSTDOCTORAL FELLOWSHIPS (2019 – 2021)
Dr Rosemary Clark University of Tasmania, TAS	Bill Gole MND Postdoctoral Fellowship 2019 – 2021	Clinical heterogeneity in ALS: insights from interneurons?
Dr James Hilton University of Melbourne, VIC	Beryl Bayley MND Postdoctoral Fellowship 2019 – 2021	Ferroxidase dysfunction drives glial ferroptotic stress and motor neurone death via neurotoxic A1 astrocyte conversion

 

MNDRIA PhD SCHOLARSHIP TOP-UP GRANTS
Courtney Clark University of Tasmania	MNDRA PhD Scholarship Top-Up Grant 2020 - 2022	Inhibitory Regulation of Motor Neurons: A new target mechanisms for MND
Laura Reale University of Tasmania	MNDRA PhD Scholarship Top-Up Grant 2020- 2022	Can we stop the spread of TDP-43 pathology in ALS?
Megan Dubowsky Flinders University, SA	MNDRA PhD Scholarship Top-Up Grant 2019 - 2021	Endogenous retroviruses as a cause of motor neurone disease
Marcus Dyer University of Tasmania, TAS	MNDRA PhD Scholarship Top-Up Grant 2019 - 2021	Neuronal excitability in ALS – a focus on TDP-43 mislocalisation

 

PROJECTS COMMENCING 2021

Betty and John Laidlaw MND Research Prize

A/Prof Yazi Ke
Macquarie University, NSW

Novel therapeutic strategies targeting TDP-43 in Motor Neuron Disease
Our research team has discovered a new, previously unidentified protein complex that appears to be involved in Motor Neurone Disease (MND). This protein complex contributes to disease processes such as nerve cell death. This proposal has three main aims: firstly, to understand how different components of this protein complex contribute to its function; secondly, to study this protein complex in an established MND mouse model to understand its disease-relevance; and, finally, to harness the knowledge of this protein complex in the development of two highly feasible therapeutic approaches in a pre-clinical setting. This project could identify new therapies for MND.
 

Bill Gole MND Postdoctoral Fellowship (2021 – 2023)

Dr Thomas Shaw
University of Queensland, QLD

Ultra-High Field MRI of Spinal Cord Tissue in Motor Neurone Diseases
Characterising differences in MND sub-types including ALS and PLS is important for understanding the disease. This project aims to distinguish these sub-types, which have separate patterns of brain and spine pathology. To achieve this, I will use Magnetic Resonance Imaging to measure tissue properties of brain and spine over time in MND patients, comparing these with clinical outcomes of disease. The project will generate significant outcomes by - for the first time - relating pathology in the brain and spinal cord to MND sub-types over time. This will increase understanding of mechanisms accounting for the irreversible progression of MND.
 

Beryl Bayley MND Postdoctoral Fellowship (2021 – 2023)

Dr Emily McCann
Macquarie University, NSW

Investigating the role of complex genomic variation in MND
Gene mutations are the only known cause of MND, however almost 90% of patients have an unidentified genetic cause of MND. Little is also known about why the clinical presentation of MND varies substantially between patients. In this project, I will use innovative bioinformatic strategies to search through the genomes of MND patients to find complex genomic changes that play a role in the cause, onset and progression of MND. Once identified, these MNDrelevant genomic changes will provide clues to how MND develops and progresses, to help patients and clinicians make informed decisions about treatment and family management strategies.

Marisa Aguis MND Postdoctoral Fellowship (2021 – 2023)

Dr Nicholas Geraghty
University of Wollongong, NSW

High-throughput flow cytometry drug screen to discover new treatments for MND
Motor Neurone Disease (MND) arises due to proteins misfolding inside motor neurone cells, leading to toxicity, cell death and loss of motor function. TDP-43 is an important protein known to misfold, leading to its clumping or “aggregating”, which causes cell death and leads to MND. This project uses a cell model in which TDP-43 forms toxic aggregates, in a high-throughput drug screen of thousands of chemicals to find potential drugs to treat MND patients. A small number of “hits” have already been identified and will be screened in animal models of MND, to identify a therapeutic to treat MND patients.

Charcot Award, funded by the NTI MND Research Grant

Dr Shyuan Ngo
University of Queensland, QLD

MND in space and time: deciphering the spatio-temporal landscape of cell-autonomous and non-cell-autonomous drivers of motor neuron death in MND
Motor neurons are usually supported by a number of different cells that sustain their function and survival. In MND, it is proposed that these support cells become toxic and contribute to the death of neurons, although we do not know how this occurs. Using mini 3D spinal cords that we have generated from MND patient skin cells, we will study how neurons and their support cells interact over time. This will allow us to generate the first “cell-to-cell communication network maps” that will give us insights into how we can manipulate this communication to save neurons from death.

Judy Mitchell MND Research Grant

Dr Victor Anggono
University of Queensland, QLD

Molecular mechanisms underlying the cytoplasmic aggregation of the RNA binding protein, SFPQ, in ALS
The mislocalisation and aggregation of RNA binding proteins are pathological hallmarks of amyotrophic lateral sclerosis (ALS). However, the molecular mechanisms underlying these aberrant processes are poorly understood. This project aims to define the molecular basis of zinc-induced cytoplasmic aggregation of an ALS-associated RNA binding protein, SFPQ. Using a combination of biochemistry, and structural and cell biology, this project will examine how two human SFPQ variants that are exclusively found in familial ALS subjects affect neuronal functions. The outcomes of this study will provide a novel conceptual framework for understanding the cytoplasmic aggregationof RNA binding proteins in ALS.

Mavis Gallienne and Graham Lang MND Victoria Research Grant

Prof David Berlowitz
University of Melbourne, VIC

REPAIR MND: REduced PAtient – ventilator asynchrony with Artificial Intelligence assisted Respiration in MND
Non-invasive ventilation (NIV), overnight breathing support with a machine and mask, is the most effective way to increase survival in MND. NIV only works if you use it and our team has shown that careful coordination of the breathing machine to the patient can convert NIV non-users into users. The coordination process is however very labour intensive and therefore challenging to translate into clinical practice. This project will build an Artificial Intelligence-based decision support tool (REPAIR MND) that will increase clinicians’ capacity to optimize NIV and usage; 20% more people with better usage is 20% more people surviving longer.

Peter Stearne Familial MND Research Grant

Prof Ian Blair
Macquarie University, NSW

Genome-wide detection of short tandem repeats that are expanded in ALS
DNA mutations are responsible for familial MND and genetic factors contribute about half the risk of developing sporadic MND. However, the genetic causes of MND are unknown in one third of MND families and most genetic risk factors are unknown. Rare expansions of DNA repeat sequences cause many other neurodegenerative diseases. Until recently we had little capacity to screen MND patients for these repeated sequences. Excitingly, this is about to change: drawing on latest technologies and bioinformatics tools, this project will screen Australian MND patients in combination with international datasets to make fresh inroads to solving the genetic basis of MND.

Robert Turnbull MND Research Grant

Dr Christopher Bye
The Florey Institute of Neuroscience and Mental Health, VIC

Next generation pre-clinical modelling for MND
Using a small skin sample from a person with MND, we can now grow motor neurons identical to those inside of that person’s body. This is an important breakthrough because we can use these motor neurons to find and test drugs to treat MND in that person. In this project, we have developed a new approach to grow these motor neurons inside a “living brain” to more accurately test potential treatments. We aim to show that this “living brain” model can accelerate the selection of drugs for clinical trials for people with MND.

Jack and Joan Thompson MND Research Grant

Dr Mouna Haidar
The Florey Institute of Neuroscience and Mental Health, VIC

Will reducing abnormal cortical activity in MND have a therapeutic effect?
Nerve cells in the motor regions (or motor neurons) of the brain carry signals to the spinal cord which in turn ommunicate with muscles to control movement. These brain motor neurons are overactive early in MND and eventually die, losing their ability to initiate and control muscle movement. We will evaluate a novel genetic approach targeted to brain motor neurons to reduce their overactivity in a mouse model of MND. Our approach uses "chemogenetic technology" to selectively reduce the overactivity of brain motor neurons. This study will encourage future use of our novel approach for the potential treatment of MND.

Col Bambrick MND Research Grant

Dr Robert Henderson​
University of Queensland, QLD

A Novel PET Imaging Marker of Astrocytes and Glutamate Reuptake in Brain and Spinal Cord in ALS

Damage to motor nerves through activation (“excitotoxicity”) is long-recognised as a potential avenue to target new therapeutics in MND. To date, there has been no reliable method to image excitotoxic injury in vivo. This novel project will test a new PET imaging method to identify key alterations in the main transporter of glutamate, the principal excitatory neurotransmitter, into glial cells in the brain and spinal cord of patients with MND. The ultimate objective is that this method will help to predict progression in individual MND patients and aid in the selection of new therapies for clinical trials.

Dr Angela Worthington MND Research Grant

Dr Colin Mahoney
University of Sydney, NSW

Establishing the role of high definition-density EEG in the diagnosis and monitoring of MND

There continues to be significant challenges in diagnosing and successfully treating those with motor neuron disease. We increasingly recognise that MND is a multi-systems disease, affecting structures beyond the motor systems, often in advance of weakness. It is crucial to develop sensitive tools to detect pathological changes across other brain regions. We will use high-density electroencephalography (EEG), to assess abnormal brain wave changes relating to both cognitive and motor processes, potentially in advance of motor weakness. The detection of early brain changes using this innovative technology may reduce diagnostic delay, and improve precision in prognosis and enrolment in clinical trials.

Run MND NSW Research Grant

Prof Pam McCombe
University of Queensland, QLD

Revisiting excitotoxicity in ALS: how does this occur?​
In MND, some of the damage to motor neurones comes about because of over-excitation. This appears to be an early event in disease. This study will examine how this occurs. We have developed novel techniques to measure amino acids that can cause over-excitation and will determine whether these are elevated in the blood of MND patients. In addition, our preliminary studies have discovered a novel molecule that helps reduce over-excitation. We will use genetic techniques to see whether variation on this molecule is associated with the clinical course of MND. This would be evidence of its involvement in MND pathogenesis.

Dr Paul Brock MND NSW Research Grant

Dr David McKenzie
University of Sydney, NSW

Development of an amperometric biosensor for the detection of TARDNA binding protein 43 (TDP-43) in MND
The underlying causes of amyotrophic lateral sclerosis (ALS, a subtype of MND) are not yet completely understood. This complicates timely and accurate diagnosis and the development of new efficient treatments. The hallmark of ALS is a protein named TDP-43 that accumulates in degenerating motor neurons of around 95% of people with ALS. We will develop a biosensor, a device that is able to detect TDP-43 in liquids, to study in future why and how this happens and if it can be reversed. In future, our biosensor can also be modified to detect other molecules relevant for ALS or other MNDs.

Jenny Simko MND Research Grant

Dr Nirma Perera
The Florey Institute of Neuroscience and Mental Health, VIC

Autophagy in Neuroglia: a hidden player in abnormal MND proteostasis
MND is characterised by accumulation of toxic protein deposits in motor neurons and surrounding neuronal supporting glial cells. Autophagy is the only pathway in our cells that can purge large protein deposits. Therapeutic rescue of autophagy to clear culprit protein aggregates may have therapeutic potential. Many studies so far have focused on exploring neuronal autophagy while glia autophagy remain unexplored. Using the powerful combination of an autophagy reporter mouse model, stem cell derived glia and post-mortem tissue, we will analyse autophagy in glia for the first time, providing new insights leading to therapeutic modulation of intricate autophagy pathway in MND.

MonSTaR MND Research Grant

Dr Frederik Steyn
University of Queensland, QLD

Targeting NAT1 to improve metabolism and slow disease progression in MND
Through working with people with ALS we have made new discoveries on a mechanism that could contribute to more rapidly progressing disease, and impairments in metabolism that are associated with rapidly progressing disease. NAT1 is an ancient protein that controls how our mitochondria respond to metabolic stress. We have found that NAT1 is linked to metabolic imbalance and faster disease progression in people with ALS. We will now conduct a world first study to understand how NAT1 modifies the body’s response to ALS. This will help reveal how we might target NAT1 to improve
outcomes in ALS.

Superball XIII MND Research Grant

A/Prof Bradley Turner
The Florey Institute of Neuroscience and Mental Health, VIC

Defining upper motor neuron markers using translational RNA profiling
There is increasing evidence that MND pathology originates from the brain and spreads to the spinal cord. Yet, the molecular makeup of motor neurons in the brain is poorly understood in MND. To unravel the mechanisms behind brain dysfunction in MND, specific molecular markers or 'sign posts' of brain motor neurons are urgently needed. This project will combine next-generation genetic sequencing technology with new genetically engineered mice to define the molecular makeup of brain motor neurons for the first time. Identifying molecules that are both specific and unique to brain motor neurons will vastly accelerate research in MND, allowing us to understand the mechanisms underlying their vulnerability to degeneration in MND and highlight pathways to potential effective treatment.

Fat Rabbit MND Research Grant

Dr Adam Walker
University of Queensland, QLD

Defining the involvement of ubiquilin-2 in MND
The mechanisms that cause the death of motor neurons in MND are still not completely understood. In this project, we will employ cutting-edge genetic engineering technology in cells to identify genes that control the pathology formed by a key MND-related protein. Importantly, unique inherited mutations in this core pathological protein also cause MND in some Australian/New Zealand families. We will analyse the mechanisms of disease related to this protein, and compare our results to human pathology. Overall, these studies will define, in an unbiased high-throughput manner, the early pathological mechanisms involved in MND.