Technology: Super vaccine crawls out of the slime

 作者:束假辑     |      日期:2019-02-28 06:16:03
By LEIGH DAYTON in SYDNEY Slime moulds, strange organisms which have characteristics of both plants and animals, could help researchers to grow the genetic material needed to produce new vaccines. Australian researchers have managed to grow genetic material in a slime mould six times faster than they can clone the genes by conventional methods. In their search for a vaccine against a group of viruses which commonly causes gastroenteritis, Keith Williams, a biologist and head of the Macquarie University Centre for Analytical Biotechnology in Sydney, has turned to the humble slime mould Dictyostelium discoideum to grow the genetic material. Gastroenteritis is widespread in developing countries, where poor sanitation enables rotaviruses – so-called because of their wheel-like shape – to spread through infected water and food, causing illness and diarrhoea in infants. Until now the basic approach has been to isolate genes for particular rotavirus proteins, clone them and insert them into animal cells. The cells produce the proteins along with their own biological products. The proteins can then be extracted from the cells for experiments. But animal cells are expensive and slow to work with. The equipment alone may cost ‘several hundred thousand dollars’ says Williams. Bacteria are cheaper, and grow faster. However, they are not a good substitute for animal cells because they do not ‘fold’, or shape, proteins in the same way: although the basic chain is the same, animal cell genes add different compounds to it, producing a protein which at the molecular level looks different from one made by a bacterial cell. This means that the viral proteins have to be carefully manipulated after bacteria have produced them before they will fool human immune systems into producing antibodies against the real rotavirus. ‘So what happens is that research (with animal cells) gets to a stage where it gets too expensive, and work stops,’ Williams says. The cells of slime moulds, however, are more like animal cells in that their walls are less defined than plants; yet they also reproduce using spores, like plants. Dictyostelium folds proteins much as animal cells do. Yet, like bacteria, it reproduces quickly, doubling in size in 3 to 4 hours. Animal cells take 24 hours to double. A rotavirus gene is inserted into a slime mould plasmid. Plasmids are free-floating rings of DNA present in bacteria and slime moulds. The plasmid is incubated overnight and then placed in a tray spread with a nutrient, agar, mixed with E. coli bacteria to feed the slime mould. ‘It’s a race,’ says Williams. ‘First the bacteria grow and eat the nutrients, and then the slime moulds come up behind and eat the bacteria.’ After three days, the scientists harvest billions of slime mould cells, each containing rotavirus protein. From every litre of nutrient, slime mould and bacteria, the team obtains 50 grams of slime mould cells – ten times the number of cells that can be grown from a litre of animal cell starter. The proteins are removed from the slime mould with a detergent which eats away the cell membrane. Researchers at Stanford University have tested extracts of the protein, and say it is as active as those produced in animal cells. However, Gerry Both, a molecular virologist with Australia’s leading research organisation, the CSIRO, is sceptical that the protein will lead to an effective vaccine: ‘It is a tough example to begin with,