We use cookies to improve your experience on our site and to show you personalised advertising. To find out more, read our privacy policy and cookie policy

Protein aggregation related diseases

Protein-aggregation related diseases

In a healthy cell, the production and degradation of protein are integrated with processes that ensure the proper folding of these proteins and the prevention of unfolded proteins aggregating. Misregulation of this balance can lead to diseases such as Parkinson’s Disease, Motor Neuron Disease and Alzheimer’s. Our researchers investigate the molecule mechanisms of protein aggregation and work on the next generation of therapies against these diseases.

Molecular Horizons is closely affiliated with The Proteostasis & Disease Research Centre (PDRC) which aims to actively promote collaborative projects and provide a supportive environment to cultivate Australian proteostasis research.

Research groups

The goal of Dr Yee Lian Chew’s research team is to use the brain of a tiny nematode worm, Caenorhabditis elegans to reveal new information about the human brain, from looking at single cells and networks to advancing our understanding of how animals can adapt and learn new behaviours. We will do this by exploiting the unique properties of the nematode model: a compact nervous system consisting of 302 neurons, unrivalled genetic accessibility and ease of maintenance. The techniques used in the lab include the generation of transgenic lines and genome editing via CRISPR/Cas, molecular biology, biochemistry and analysis of behavioural changes/learning paradigms. Ultimately, the information derived from C. elegans is hoped to advance knowledge on the fundamental biological basis of neurological conditions in humans such as chronic pain and neurodegenerative disease.

Yee Lian has spent the last 9 years of her life trying to understand life through the worm: she did her PhD at the University of Sydney (2011-2014) and moved to the Laboratory of Molecular Biology in Cambridge, UK (2015-2019) to study worms in colder weather. She joined the University of Wollongong and Illawarra Health and Medical Research Institute (IHMRI) in January 2019.

 

"A transparent nematode C. elegans (and eggs), with red and green fluorescence marking different tissues in the body, including neurons in the head (middle of image). The fluorescent markers indicate where signalling molecules via a particular neuropeptide (red) or dopamine (green) are expressed. Fluorescent tools like these help researchers to dissect which neurons make up circuits in the brain that control the animal's behaviour." Photo taken by Y. Chew using Zeiss LSM 780 confocal microscope at the MRC Laboratory of Molecular Biology, Cambridge UK.

View Dr Yee Lian Chew's Scholars page

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

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.

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.

Close