Researchers in this theme focus on unravelling the underlying mechanisms that contribute to the onset and progression of MND. We particularly focus on investigating genetic contributions, protein misfolding, mitochondrial dysfunction, neuroinflammation, ion channel dysfunction, cellular stress, altered communication between neurons and muscle, and extracellular vesicles (among many others). As a collective, we use patient tissues, in vitro cell models, and animal models to understand what might be driving disease, and their role in MND. This knowledge is important because it can be used to develop better treatments for MND.
Genetic pathways
Researchers investigate key MND-linked genes such as SOD1, C9orf72, and TARDBP and their contributions to MND. We can introduce gene variants into cells or animal models (e.g. flies, zebrafish) to determine the extent to which they might contribute to MND. We also use a suite of bioinformatics and genetic sequencing tools (genome wide association studies, whole genome sequencing, spatial transcriptomics) to identify novel genetic contributions to MND. Many of these identified pathways lead into a better understanding of the cellular and/or molecular factors that are involved in MND.
Cellular and molecular pathways
Researchers investigate how cellular pathways within motor neurons and between other cell types (such as glia and skeletal muscle) contribute to motor neuron degeneration. These pathways include processes such protein aggregation, mitochondrial dysfunction, and inflammation. Techniques such as CRISPR-Cas9 gene editing, live cell imaging, high throughput screening and proteomics, are used to generate data that can be combined to build a clearer picture of how cell pathways might come together to cause motor neuron death. We routinely use animal models of MND as well as stem cell derived neurons, and stem cell derived mini 3D brains and spinal cords to understand when and where (in which cells) these cellular pathways go awry.
Researchers can also investigate the finer details within cellular pathways by identifying molecular interactions within cells that affect motor neuron function and survival. Pathways such as transport, metabolism, and DNA replication and repair are investigated. Novel techniques have been developed to study the interactions between proteins, lipids, and nucleic acids. We use our animal models of MND, stem cell derived neurons, and stem cell derived mini 3D brains and spinal cords to then manipulate these molecular pathways to determine whether they have positive or negative impacts in the disease.
Why our research matters
Our multifaceted approach to understanding disease mechanisms in multiple pre-clinical models of MND is critical because it allows us to:
- Identify key therapeutic targets for developing effective and targeted treatments that can move through our translational pipeline, ultimately leading to a cure
- Leverage our collaborations with leading scientists and clinicians around the world, ensuring that our findings translate into clinical trials for patients and real-world applications.
Our team
- Associate Professor Mark Bellingham – an electrophysiologist with an interest in studying how increased activity of neurons contributes to MND
- Dr Fernanda Cardoso – a pharmacologist who is interested in determining whether venoms (e.g. spider venoms) can be used to modify the activity of neurons
- Professor Elizabeth Coulson – an expert in investigating how and why certain neurons die in neurodegenerative diseases
- Dr Fleur Garton – using genetic risk factors, polygenic scores, and blood-based omics to understand how these contribute to MND
- Dr Jean Giacomotto – developing laboratory models to understand how genes mutations might underpin MND
- Dr John Lee – a neuroscientist with additional training in immunology who is interested in understanding how inflammation impacts MND
- Dr Allan McRae – expert in statistical genomics and in using large-scale genetic/’omic data to pinpoint drivers of MND
- Professor Mark Midwinter – Professor of clinical anatomy contributing to studies aiming to determining the role of skeletal muscle in MND
- Associate Professor Sean Millard – developing laboratory models to understand how genes mutations might underpin MND
- Associate Professor Dominic Ng – a cell biologist interested in uncovering the molecular mechanisms of MND
- Associate Professor Shyuan Ngo – a biomedical researcher and neuroscientist who is studying a range of potential disease mechanisms for therapeutic development
- Associate Professor Peter Noakes – a neuroscientist who has a strong focus on understanding how skeletal muscle impacts MND
- Dr Margreet Ridder – an electrophysiologist who is focusing on studying the activity of neurons and how this can be targeted to improve their survival
- Dr Daniel Schweitzer – a neurologist with an interest in understanding how gene variants and changes in physiological processes contribute to MND
- Associate Professor Adam Walker – a neuroscientists who is focused on understanding why and how toxic proteins form clumps in neurons
- Associate Professor Anthony White – a neuroscientist with an interest in understanding the role of inflammation in MND
- Associate Professor Joy Wolfram – an expert in extracellular vesicles (EVs) who is aiming to understand whether (EVs) from certain cell types might be playing a role in MND
- Professor Trent Woodruff – a pharmacologist interested in understanding and developing treatments against inflammation in MND
- Professor Naomi Wray – leader in statistical genetics, guiding direction/analyses of large-scale genetic data to identify causes for MND
- Dr Alain Wuethrich – a physicist and bioengineer who is interested in uncovering the role of extracellular vesicles in MND