In Brief Australian decision on stem cell use Australian Prime Minister John Howard, has produced an agreement between himself and the Australian state and territory leaders on the use of stem cells and cloning in humans. Scientists will have the right to use spare embryos from in vitro fertilization programmes for research, but nuclear transfer technology and therapeutic cloning will be banned. An ethics committee will consider how to ensure that embryos are created only for in vitro fertilization and not just for research. The Australian 5April (2002), p. 4 DM Yeast ‘localizome’ in vitro Anuj Kumar et al., report on a large scale analysis of proteins (the proteome) in baker’s yeast, Saccharomyces cerevisiae. Although the S. cerevisiae genome sequence was completed in 1996, over a third of the protein products encoded by the 6000 genes are yet to be assigned a function. Because subcellular localization is a strong indicator of protein function, a high-throughput method to tag individual proteins and visualize their movements within living cells was developed, successfully determining the subcellular location – ‘localizome’ – of over 2700 yeast proteins.The work provided an insight into the potential function of nearly half of all previously uncharacterized yeast proteins. For more information there is a database containing the results of the work: http://ygac.med.yale.edu. (Genes Dev. 16, 707–719) DM Sleeping beauty transformed For the first time, a transposon (called Sleeping Beauty) has been used to genetically modify a vertebrate animal. Adam J. Dupuy et al. injected the transposon containing the gene for a yellow coat colour into a mouse embryo, resulting in a genetically modified mouse. ‘We’re very excited about Sleeping Beauty’s potential,’ said David Largaespada, group leader for the project. ‘One use would be to add genes to germ cells or early embryos in order to produce large amounts of a protein in an animal.The protein then would be purified and used as a drug treatment for hemophilia, for instance.’ Largaespada is TRENDS in Biotechnology Vol.20 No.6 June 2002 http://tibtech.trends.com 0167-7799/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. 235 News& Comment Cellular prion protein (PrP C ) is a cell-surface protein expressed mostly by neural tissue. Although its precise function is unknown, among the possibilities is a role in copper metabolism. An abnormal conformation of the protein (PrP Sc ) is believed to be the causative agent of prion diseases.These are fatal neurodegenerative disorders in which neuronal loss and overgrowth of glial fibres occur after long, seemingly asymptomatic, incubation periods. It seems that expression of PrP C is necessary for the manifestation of prion disease, as genetically modified mice that fail to express it are resistant to infection with mouse prion inoculum. However, exactly how the conformational change from PrP C to PrP Sc leads to neurodegeneration is not understood. PrP C is a copper-binding protein.To further elucidate the role of metals in prion disease,Thackray et al. [1] investigated whether there were changes in trace elements in the brains, and other organs, of mice infected with mouse scrapie. Interestingly, the authors found changes in the levels of copper and manganese in the brains of infected mice, prior to the onset of clinical symptoms. Specifically, they observed a reduction in brain copper and significantly elevated levels in the liver and blood, suggesting a displacement of copper from the brain or other tissues. Changes in manganese were more widespread, with elevated levels occurring in blood, brain and muscle. Of particular note was the increase in brain manganese relative to the decrease in copper.The change reached its maximum at the onset of clinical signs.This constitutes the first report of a neurodegenerative disease in which there is a systemic change in manganese, perhaps signifying a characteristic that will allow selective diagnosis of prion disease. It has been suggested that prions are antioxidant proteins.Therefore, the authors investigated whether there were also changes in antioxidant proteins associated with disease progression.They found that whereas expression levels of both copper/zinc-superoxide dismutase (SOD) and manganese-SOD are not altered by prion disease, the activity of the enzymes is affected. Both purified and recombinant PrP C are believed to have a catalytic activity similar to SOD, which is a copper-dependent enzyme.The metal content and level of PrP-dependent SOD activity in purified proteins was therefore assessed. During infection, inoculated mice showed a loss of bound copper and an increase in associated manganese, together with a significant decrease in SOD-like activity.The decrease in activity matched the decrease in copper, implying a reduction in copper and antioxidant activity of the total PrP content. Manganese binding to PrP C is known to stimulate its conversion into an abnormal conformation rich in β-sheets, and it was thought that an imbalance in brain trace elements could lead to the formation of PrP Sc . This study suggests that scrapie-induced prion disease might cause such a change in the brain, and therefore a metal imbalance could induce conversion of PrP C into PrP Sc . Thackray et al. therefore postulate that alterations in trace-element metabolism arising from changes in metal binding to PrP are central to the pathological modifications characteristic of prion disease. Further analysis of the alterations are necessary, but the implication is that these values might represent specific changes with immediate diagnostic potential. 1 Thackray, A.M. et al. (2002) Metal imbalance and compromised antioxidant function are early changes in prion disease. Biochem. J. 362, 253–258 Teresa K.Attwood attwood@bioinf.man.ac.uk M etals in prion disease