Quick Project Snapshot

New animal models of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common age-related dementia, with the number of affected individuals expected to exceed 100 million worldwide by 2050. In Australia, Alzheimer’s disease is the third leading cause of death behind heart disease and cancer. Despite the significance of this disease there are currently no disease modifying drugs to treat Alzheimer’s disease.

One of the pathological hallmarks of Alzheimer’s disease is the cerebral deposition of plaques composed of Amyloid-beta (Aß) peptide. Aß is produced by sequential proteolytic cleavage of the ubiquitously expressed integral-membrane protein, amyloid ß-protein precursor. The Aß released typically ranges from 38 to 43 amino acids in length due to imprecise cleavage. Peptides Aß1-40 and Aß1-42 are two of the most common forms and have received the majority of research attention. Clearance of Aß is slowed in cerebrospinal fluid from Alzheimer’s disease patients, which likely contributes to its pathological deposition. The accumulation of Aß is thought to lead to disease progression, however, the underlying mechanism of Aß toxicity remains unclear.

The nematode, Caenorhabditis elegans offers a simplified in vivo system in which to examine Aß toxicity and its modulation.

 

 

Figure: Staining of amyoid deposits in C. elegans. A) Controls and B) Aß1-42 expressing strain.

 

The project: We have developed new transgenic C. elegans strains expressing specific disease relevant amino-truncated Aß-species.

·      The in vivo aggregation and oligomerization properties, and toxicity of these Aßx-42 transgenes will be compared.

·      C. elegans lines will be examined for rescue of the toxicity phenotypes by genetic interaction studies, to identify new therapeutic opportunities.

 

 

Suitable for PhD or MSc

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HEAD OF LAB
Dr Gawain Mccoll

Molecular Gerontology Laboratory

Ageing is universal in multicellular organisms. How ageing and lifespan can be modulated is an area of significant scientific interest. By reducing complexity and time scale, the study of simple organisms has provided a wealth of information about the biochemical systems that contribute to the ageing process. The nematode, Caenorhabditis elegans has numerous advantages for the study of the biology of ageing.

These nematodes are microscopic (~1 mm), self-fertilizing, free living, and easily cultured in the laboratory. Benefits of this model system include: a short three-day life cycle, 14-day natural lifespan, highly developed genetic tools, fully characterised cell lineage, and an open research community. Despite its simplicity, conservation of genetic and disease pathways between C. elegans and higher eukaryotes make it an effective in vivo model for study ageing and disease pathogenesis and the preeminent model system for genetic manipulation of ageing.

Work using this model first demonstrated that single genes and compounds could dramatically modulate life span and the rate of ageing.

All Projects by this Lab

Rapid animal models of Parkinson’s diseaseNew animal models of Alzheimer’s diseaseIron and Biological AgeingSupport Cells and Dopaminergic Neurons
CO-HEAD OF DIVISION

Professor Philip Beart

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CO-HEAD OF DIVISION

Prof Colin Masters

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Biophysics Laboratory

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HEAD OF LAB
Dr Simon Drew

Oxidation Biology Unit

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HEAD OF LAB
Prof Ashley Bush

Prana Laboratory

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Dr Robert Cherny

Neurodegeneration

Scientists in the Neurodegeneration division interrogate how neurones live, die and can be rescued to improve brain function in degenerative conditions such as Parkinson’s and Motor Neuron Diseases. There is no effective treatment for Motor Neurone Disease and the incidence of Parkinson’s Disease is rising alarmingly in our aging community. Gene abnormalities, energy deprivation, toxic rubbish accumulation and inflammation all contribute to a toxic environment for brain cells. Our teams study these events in animal models and cultured cells, with a view to translating knowledge into new therapies for human patients.

All Labs that operate in this Division

Atomic Pathology LaboratoryBiophysics LaboratoryCellular Neurodegeneration LaboratoryCreutzfeldt Jakob Disease Clinical Research GroupMolecular Gerontology LaboratoryMotor Neurone Disease LaboratoryNational Dementia Diagnostics LaboratoryNeurochemistry of Metal IonsNeurogenesis and Neural Transplantation LaboratoryNeuropathology and Neurodegeneration LaboratoryNeuroproteomics and Metalloproteomics LaboratoryNeurotherapeutics LaboratoryOxidation Biology UnitParkinson's Disease LaboratoryPrana LaboratoryPre-clinical Parkinson’s Disease Research LaboratoryPresynaptic Physiology Stem Cells and Neural Development LaboratorySteroid Neurobiology LaboratorySynaptic Neurobiology LaboratoryThe Australian Imaging Biomarker and Lifestyle Study (AIBL)