Molecular Neuroscience and Neurodegeneration

Molecular Neuroscience and Neurodegeneration

The human brain is complex in its structure, function and development. Disorders and diseases of the brain and nervous system impact individuals and society on many levels. Our teams of world-class researchers engage with the global community, employing cutting-edge technologies that enable analysis on an unprecedented scale. We investigate the building blocks of the brain to understand how it works, improve accurate diagnoses of brain illnesses, and to discover the preventions, treatments, and cures of the future. 

Research groups

Emerging evidence suggests ancient viral sequences which make up almost 10% of our DNA, known as endogenous retroviruses, contribute to the appearance and spreading of molecular clumps throughout the brain. This ‘clumping’, or aggregation, is a central signature of many neurodegenerative disorders including Alzheimer’s and Motor Neuron (MND) diseases. Our mission is to understand the Neurobiology of Endogenous RetroViruses in both health and disease: we are the NERVLAB! Our team is developing a unique molecular toolbox spanning orders of magnitude, from single molecules to whole proteomes, which allows us to quantify and characterise ERVs in complex biological samples in unprecedented detail.

We are using this cutting-edge toolbox, combining super-resolution microscopy and proteomic techniques, to identify specific ERV signatures in patient-derived biofluids, to benchmark experimental models, and to explore the interplay between genetic diversity, aggregation and ERV expression in the context of neurodegeneration. Our ultimate goal is to translate these fundamental insights into novel diagnostic and therapeutic strategies with the potential to have tangible impact on the lives of those living with MND worldwide.

View Dr Dezerae Cox's Scholars page

Contact dezerae_cox@uow.edu.au for more information.

Our research integrates technologies in human pluripotent stem cell (hPSC) biology, neuroscience, and bioengineering to create cellular models of the human nervous system. Specifically, we work on establishing new techniques for differentiating hPSCs into various neural lineages, such as dorsal root ganglia sensory neurons, cortical neurons and auditory neurons. Our work plays a pivotal role in advancing our understanding of human neurodevelopment and has impact on regenerative medicine applications for neurological disorders, specifically Friedreich's ataxia (FA) and hearing loss.

Our laboratory has also developed valuable tools for collaborative research in modelling neurodegenerative conditions. This includes generation of NGN2 transgenic hPSC lines, which allows for rapid conversion of neurons in vitro (following the protocol of Fernandopulle et al.). Our transgenic hPSC lines includes FA induced pluripotent stem cell lines (iPSC) and their corresponding isogenic control iPSC lines, that were developed by Dr Marek Napierala (owned by University of Alabama, USA). The transgenic cell lines have been applied to study disease mechanisms underlying FA and to test potential therapeutic interventions, including candidate pharmaceutical compounds and gene therapy.

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The Ecroyd research focus is in the field of protein homeostasis (proteostasis), an important area of research as disturbances in proteostasis can lead to protein aggregation (i.e. the clumping of proteins into large deposits), a pathological hallmark of many human diseases, including Alzheimer’s disease, Parkinson’s disease and Motor Neurone Disease (MND). Research in the Ecroyd lab focuses on the role of molecular chaperone proteins in proteostasis. This is because these are the body’s front-line defenders against protein aggregation. By identifying innovative approaches to activate molecular chaperones, the group aims to develop new drugs to treat, and ultimately prevent, neurodegenerative diseases such as MND.

Work currently being undertaken in this laboratory extends from molecular biology-based techniques to recombinant protein expression and purification, in vitro biochemical assays of chaperone protein activity, to mammalian cell culture and the study of protein expression and modification in animal tissues. Of late, my group has been involved in developing novel techniques to study heat-shock chaperone function in cells and a flow cytometry-based method to count and physically isolate protein inclusions from cells. The group are also developing new single-molecule approaches so that, for the first time, we can see and characterise the interactions between heat-shock proteins and aggregation-prone proteins.

The small heat shock protein Hsp27 (HSPB1) bound to the surface of an a-synuclein amyloid fibril. This image was obtained using Total Internal Reflection Fluoresence (TIRF) microscopy. We think, by binding to amyloid fibrils, these molecular chaperones protect the cell from their toxic effects.

View Professor Heath Ecroyd's Scholars page

Contact heathe@uow.edu.au for more information.

Humans are experiencing stress at higher levels than ever before. In the developed world, this appears to be a product of our way of life, where we are busier than ever yet more isolated from our natural environments and communities. In other places, war, conflict, climate change and environmental disasters are displacing people from their homes and countries at unprecedented rates.

Stress is not always bad for us. It’s what gets us out of bed and gives us laser focus. Yet stress that is stronger than an individual’s ability to adapt and cope is one of the leading risk factors for developing severe mental illnesses including depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, and anxiety. In fact, the World Health Organisation predicts that by 2030, one third of all disease burden in the world will be caused by stress.

We are therefore at a crossroad. We urgently need an improved understanding of the detailed and widespread effects of stress on human biology, so that we can identify people who are vulnerable to the effects of stress and improve their resilience. To do this, we must first understand what are the biological effects of stress and how does stress raise risk to mental illness.

An inverse Colgi-cox stained image of the human brain cortex by Dominical Kaul

Our goal

The Matosin Lab broadly aims to understand how stress contributes to the development of mental illness. The lab has two main streams:

  1. In the first stream, we aim to understand what happens to the cells and molecules in the human brain after stress exposure or in mental illness. To do this, we study human brains donated to science by people who used to live with a mental illness and/or had very stressful lives. Tiny slivers of brain or pieces no larger than the size of a pea are used to pinpoint differences in the shapes, numbers, orientation and connections of brain cells, as well as what is happening inside them from the level of the gene to the protein. This research provides the fundamental knowledge needed to develop new treatments and interventions.
  2. In the second stream, we aim to understand what are the long-term and sustained effects of stress on the human body, and then to build a framework for identifying people who are at risk to mental illness and ways to improve their resilience. Our group is also interested in how the effects of stress and trauma can be transmitted from parent to offspring, therefore having transgenerational impact. To address these questions, we study biological samples  – including saliva, mouth swabs, blood, and breast milk – and psychological data from people and communities who have been heavily stress exposed. By studying human tissues and fluids that are easily accessible and minimally invasive to collect, this research provides the possibility to develop ways to (a) screen for people at risk to the detrimental effects of stress, (b) identify who could benefit from specific treatments and interventions, and (c) design those treatment and interventions.

Our values in and out of the lab

Scientific excellence, impactful research, collaboration, openness and authenticity, training and connecting the next generation of scientists with world leaders, enthusiasm, creating an environment that is positive and encourages teamwork and generosity.

View Dr Natalie Matosin's Scholars page

Contact nmatosin@uow.edu.au for more information.

The Vine‐Perrow Lab is a dynamic and innovative research group dedicated to advancing the understanding and treatment of motor neuron disease (MND). Our research efforts are driven by an urgent need to address the challenges faced in the development of effective treatments for MND. Over the past two decades, the majority of clinical trials for MND have yielded disappointing results, primarily due to significant barriers in therapeutic agent bioavailability, inefficient delivery to the central nervous system (CNS), and complexities in therapeutic administration. My lab draws from longstanding experience in developing targeted therapies for cancer to overcome the challenges posed by the blood‐brain barrier (BBB) and blood‐spinal cord barrier (BSCB) to enable effective delivery of systemically administered agents to the CNS. Specifically, we focus on the delivery of antisense oligonucleotides to the CNS using calcium phosphate lipid nanoparticles in combination with focused ultrasound, a non‐invasive method to transiently and safety open the BBB and improve drug delivery to the CNS. Our team employs a multidisciplinary approach, combining expertise in cell and molecular biology, nanotechnology and focused ultrasound to develop innovative solutions for the treatment of MND.

The Wilson research group is focussed on both basic and applied science relating to chaperones and protein folding, with a special emphasis on a novel group of (normally secreted) extracellular chaperones discovered by us. We reported the first known extracellular chaperone in mammals (clusterin) and have continued to discover new examples of this small but growing family of important molecules. Our studies include in vitro structure-function studies of extracellular chaperones, and also encompass work in small animal models (Drosophila, zebrafish and C. elegans) addressing basic science questions and specific disease scenarios. We have also developed new fluorescence-based technology platforms, including a high-throughput flow cytometry system currently being applied in a search for novel drugs to treat motor neurone disease.

A 3-colour image of a stressed cell: nucleus (blue), endoplasmic reticulum (red) and a chaperone (BiP; green)

View Senior Professor Mark Wilson's Scholars page

Contact mrw@uow.edu.au for more information.

The Yerbury lab is dedicated to understanding the molecular mechanisms underpinning Motor Neurone Disease (MND), with a particular focus on protein misfolding and protein aggregation. Utilising a broad array of methods ranging from the fields of biophysics, biochemistry, and cell and molecular biology, we study the basic biological processes that lead to protein aggregation, with the aim of identifying and developing novel therapeutic strategies for the treatment of MND.

Currently, we are developing a powerful high-throughput microscopy method to screen novel and clinically-approved compounds for their protective properties against MND-related protein aggregation in cultured cells. Utilising this approach, we are able to identify clinically-translatable compounds and assess their therapeutic potential in preclinical models, in an effort to uncover novel treatment avenues for MND.

Motor neurons in culture captured using confocal microscopy (Christen Chisholm, PhD candidate)

View Professor Justin Yerbury's Scholars page

Contact jjyerbury@googlemail.com for more information.