Macquarie University Neurodegenerative Disease Biobank
All people living with MND who attend the clinic, together with their families and supporters, are invited to contribute to this invaluable resource. DNA, RNA, plasma, serum, urine, hair, skin, and, when appropriate, post mortem tissue are collected and stored with ongoing analysis in various projects. This resource has grown rapidly with more than 575 people participating and over 17,000 samples collected. The unique nature of the biobank includes multiple sampling at intervals to investigate how the disease progresses, and the interdigitation with clinical records of progression and disease phenotype. This is the well-spring of our research.
Cell Culture Models of MND
Our cell culture facility is within a physical containment 2 (PC2) laboratory and is designed to accommodate the culture of mammalian cell lines and primary cells. The facility has biological safety cabinets (four) for the sterile handling of cells, as well as several atmosphere-controlled (CO2) incubators with HEPA air filtration system for growing cells. Phase-contrast, fluorescence, standard bright-field microscopes, as well as cell counters are available for cell analysis. The Class II biological safety cabinet provides protection for personnel, environment and products who work with genetically modified microorganisms (GMOs). The cell culture resources are purposed for transient and stable transfection and/or lentiviral transduction of MND/FTD genes of interest that enable us to comprehensively study their effects in in vitro and ex vivo systems.
The genomic analysis team is building resources for the analysis of genomic variability in ALS and FTD, with a high level of both human and technological capacity. Current resources build on our BioBank platform to provide Whole Genome Sequencing in familial and sporadic ALS/FTD, Whole Exome Sequencing in familial ALS, as well as transcriptomic and methylomic profiling. These are critical resources for identifying the genetic and genomic basis of the onset and progression of familial and sporadic ALS and FTD. Our genomic analysis in ALS and FTD is funded in part by the by an NHMRC Demetia Research Teams Grant.
The faculty microscope facility is built with the state-of-the-art instruments for single molecule, cell, tissue, organelle and whole animal imaging. These include multichannel confocal systems that allow superresolution airyscan and live cell time-lapse imaging for short or long term experiments and a number of upright microscope platforms that are capable of high resolution transmitted light and epifluorescence imaging. In addition, the faculty also provides tools such as Imaris for post image analysis.
The Centre has access to leading edge proteomics infrastructure at the Australian Proteome Analysis Facility (APAF) to assist the MND and neurodegenerative diseases research community to facilitate collaboration and provide solutions for proteomics needs. The Centre have expert staff dedicated to managing the proteomics pipeline to facilitate the gene discovery and biomarker platforms to provide unbiased, high-throughput, and quality analysis of biological changes. Our proteomics pipeline aims to maximise the potential of MND research projects, some of which may include an in-depth analysis of cell pathways affected from candidate MND genes, environmental stressors, or potential therapies, to name a few. We invite the MND and neurodegenerative diseases community to collaborate and discuss their projects that may have utility for proteomics.
Transgenic Mouse Models of MND
The Centre manages and makes use of several well-established MND mouse models, including genetically modified SOD1 and TDP-43 mice. We have extensive expertise in histological, biochemical and behavioural studies in these animals, with the goal of understanding disease and finding new treatments for people living with MND. We regularly perform motor testing (grip strength and movement tasks) as well as pre-clinical studies including testing of potential new therapeutic compounds, administered via oral route, injection or stereotaxic surgery in mice. All our mouse studies are assessed by the Macquarie University Animal Ethics Committee and conform to the 'Australian code for care and use of animals for scientific purposes'. We take care to reduce the number of animals, refine our experimental procedures and replace the use of animals in experiments wherever possible, while maintaining an effective pre-clinical pipeline aimed at delivering new therapeutics to people living with MND as soon as possible.
Our state of the art zebrafish facility is located within an aquatic physical containment 2 (PC2) laboratory inside the larger PC2 laboratory. The facility has been specifically designed to facilitate all aspects of zebrafish work and includes microinjection facilities, microscope facilities, behavioral tracking facilities, zebrafish breeding, training services, zebrafish agistment and cryogenic freezing. The facility houses and breeds genetically modified transgenic, mutant and wild-type strains of zebrafish in an Aquatic PC2 space. The three microinjection stations allow for the generation of transient, stable, knockdown or knockout zebrafish models. The microscope facilities offer access to a range of microscopes; from phenotyping microscopes up to high end confocal and live imaging microscopes. The zebrafish resources are purposed for the facilitation of studying all aspects of MND/FTD and their modifiers in an in vivo vertebrate system.