Taking Risks


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Prof. Naama Barkai. Experiment in evolution
Every time a scientist embarks on a new experiment, he or she is taking a chance: The results are never known in advance, and all possibilities are open. Nature, in this sense, is a great laboratory; the forces of evolution are continually taking chances on their experiments with living organisms.
Cells can be thought of as basic subjects for evolution’s experiments: Changes in a tiny molecule here or there can have far-reaching, unpredictable consequences for the cell, and for the organism as a whole. Scientists, as well, have often adopted cells as their subject matter and, through their research, they are discovering how the rules governing experimentation in nature have evolved over the millennia.
Prof. Naama Barkai and her research team in the Institute’s Molecular Genetics Department, for example, have revealed a principle that evolution uses in designing experiments. The stakes are often high: A failed experiment in the cell can mean death for the organism, while a successful one can give the organism an edge in the survival game. In this light, it’s not too surprising that some genes have hardly been touched by evolution – they’ve been conserved from single-celled yeast through plants and worms right up to humans – while others have been changed many times over. Clearly, the conserved genes have some basic, universal function for life, and rearranging them for the sake of an experiment would have drastic consequences for the organism. But how does evolution “decide” which genes to conserve and which can be test cases for change? How are the genes that need to be conserved spared the constant fiddling that affects their neighbors in nature’s lab?
The scientists found that genes have evolved a sort of labeling system that can indicate the level of risk associated with making changes in the expression of a particular gene. The label is a short sequence of letters in the gene code, TATA, which is found in the promoter regions where the genes are activated. A gene that displays a TATA box in its promoter is more likely to have evolved its expression – a signal that it’s open to taking a risk on experimentation.
That risk, say the researchers, can be calculated very much like a financial “risk distribution law,” which is based on the cost of an error. If that cost is high, the investor will be less willing to take a risk, even if the chances of an error are low. Conversely, a low cost for an error, even if there’s a good chance one will be made, will make the investment – or the experiment – more attractive.
Evolution sometimes performs a more drastic experiment on living cells: The whole genome is doubled. In a second line of research, Barkai and her team compared two species of yeast. One of these species had undergone genome doubling millions of years ago, a feat that profoundly affected the yeast’s lifestyle: It gained the ability to grow and thrive without oxygen. To uncover the connection between such a change in gene expression and lifestyle, the scientists singled out and compared 50 genes that are involved in oxygen use in both yeast species. They discovered one gene segment – a bit that regulates the expression of the other oxygen-processing genes – that had changed in the course of the gene doubling. This small change, because it affected so many other genes, dramatically altered the oxygen requirements of the yeast.
The payoff for this natural experiment is open to interpretation: It probably allowed this type of yeast to expand into new environmental niches, giving it an advantage over its sister species in places where oxygen was scarce. In the future, changing environmental conditions might again favor one over the other, or they might support the survival of yet other species that are still to come out of the great, ongoing experiment called evolution.   
Prof. Naama Barkai’s research is supported by the Helen and Martin Kimmel Award for Innovative Investigation; the Carolito Stiftung; the Minna James Heineman Stiftung; and the PW-Iris Foundation.

Innovation Prize

A sort of risk distribution law often seems to apply to the grant approval and funding processes in science. All too often, grants are given to research proposals that entail minimal risk: Even though the gains may be proportionately small, chances are the research will yield the expected results. In contrast, scientists engaging in research that is “high-risk, high-gain,” may not even be able to define the expected outcome of a particular line of research to the satisfaction of a grants committee, much less offer guaranteed results for the money.
Nonetheless, true leaps in science are more likely to come out of research that explores the truly unknown or attacks a question from a completely new angle, with few prior clues as to what that research will yield. To encourage scientists who undertake high-risk, high-gain research, the Weizmann Institute, together with the Kimmel family, have come up with a promising concept: Fund the exceptional scientist, rather than the specific research. To this end, they created the Helen and Martin Kimmel Award for Innovative Investigation.
This past  November, Prof. Naama Barkai became the first recipient of this annual award. She receives one million dollars, spread over five years, to continue to research wherever her curiosity leads her.