2011 Postgraduate Research Competition - UNSW Science - The ...

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Yeast genome-wide analysis identifies cellular
processes affecting aggregation of amyloid beta
42-GFP fusion reporter
Suresh Nair and Ian Dawes
School of Biotechnology & Biomolecular Sciences
Abstract
Alzheimer’s disease (AD) is the leading cause of dementia in individuals over 65 years of age;
and the risk of developing Alzheimer’s disease increases steadily with age. Amyloid-beta (Aβ)
plaques, composed of aggregates of Aβ peptides, are a major neuropathological feature of
AD. The two major isoforms of Aβ peptide are Aβ40 and Aβ42, of which the latter is highly
prone to aggregation and shown to support a central role in AD disease progression. The
increased presence and aggregation of intracellular Aβ42 peptides has been shown to be
an early event in the disease progression of AD. Improved understanding of cellular
processes involved in Aβ42 aggregation may have implications for our understanding of AD
disease progression and possible development of therapeutic strategies.
In this study, Aβ42 fused to GFP (Aβ42GFP) was expressed in each mutant of the
Saccharomyces cerevisiae genome-wide deletion library, to identify on a genome-wide
scale the proteins and cellular processes that affect intracellular Aβ42 aggregation by
assessing the fluorescence associated with the Aβ42GFP reporter. The genome-wide
screening identified 98 mutants exhibiting intense Aβ42GFP-associated fluorescence. These
deletion mutants were categorised according to broad biological functional groups/cellular
processes based on the established or putative cellular roles of each of the respective 98
gene products. This approach identified four major cellular processes that were overrepresented
in the data set, of which mutants that were categorised into the lipid
homeostasis functional group is discussed.
Abstract
Are tear proteins essential for good vision
Siva Balasubramanian and David Pye
School of Optometry & Vision Science
Human tears are rich in proteins and help to provide nourishment to the cornea, which is
located at the front of the eye. A normal spherical cornea is essential for good vision.
Keratoconus is a disease condition which alters the corneal shape and can therefore
produce severe visual impairment.
Thin capillary tubes were used to collect human tears and shape of the subject’s corneas
was measured. The total proteins and major individual proteins in human tears were
analyzed. The association between tear proteins and severity of keratoconus was studied.
The tears of people with keratoconus were deficient in certain tear proteins and these levels
decreased as the disease progressed.
Since tears are spread over the cornea, the tear proteins might affect, or be affected by the
altered corneal shape in Keratoconus. Appreciating the cause for low levels of tear proteins
might be vital to slow or prevent vision loss from this condition.
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