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
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 LabRapid animal models of Parkinson’s diseaseNew animal models of Alzheimer’s diseaseIron and Biological AgeingSupport Cells and Dopaminergic Neurons
Dr Lachlan Thompson
Prof David Finkelstein
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.