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Study of Life’s Blueprint Wins Prestigious $25,000 Young
Scientist Prize Awarded by Amersham Biosciences and Science
For his study of life's genetic blueprint, Lei Wang, a post-doctoral researcher at the University of California-San Diego, has been named to receive the prestigious $25,000 Young Scientist Prize, awarded by Amersham Biosciences and the journal, Science.
Now 31 years old, Wang was working at UC-Berkeley, guided by Prof. Peter G. Schultz (currently at the Scripps Research Institute) when he became fascinated with fundamental questions:
Why, for example, do all life forms use the same 20 amino acids to build proteins? Is life's blueprint a genetic fossil, accidentally frozen before it could code for more amino acids? Or, is modern DNA an expanded version of its shorter, primordial blueprint?
Wang, a native of Tonggu, China now living in La Jolla, California, ultimately developed a method for inserting an extra amino acid into a protein in live cells, in the same way that natural amino acids are incorporated. The research thus produces a living or "in vivo" means for studying the evolution of genetic code, and for probing life processes.
Indeed, Schultz said, Wang's research sets the stage for highly specific genetic engineering, thus opening new research horizons: "His work will likely make possible the generation of proteins, and perhaps entire organisms with novel properties not limited by the 20 common amino acids."
"We were able to show, for the first time, how the genetic code could indeed be expanded by human power, using nature's technique," said Wang. "In a way, our methods remove the constraints of nature, suggesting exciting opportunities for studying and engineering various biological functions."
Using the bacterium E. coli as a host, Wang designed and engineered a new set of components including nucleic acids and enzymes. A "nonsense codon"a trio of bases that codes for nothingwas hijacked to serve as the trigger or signal. These new building blocks, when added into the cell machinery, selectively insert a new amino acid into proteins in response to the signal. The research resulted in an article in Science (20 April 2001) describing the method and the first bug with an expanded genetic code. In follow-up work by other researchers, the system and strategy were transplanted from the bacterium into mammalian cells (Nucleic Acids Research, 1 November 2002) and yeast (Science, 15 August 2003).
"The standard of this year's entries to the Young Scientist Prize has been impressive. The studies carried out by Lei Wang and the other entrants demonstrate the talent that exists amongst the young scientific community," said Andrew Carr, President Discovery Systems, Amersham Biosciences. "This prize is dedicated to recognizing the scientists who will be at the forefront of molecular medicine in the future."
Amersham Biosciences and Science established the Young Scientist Prize in 1995 to support fundamental discoveries in the field of molecular biology.
"Supporting scientists at the beginning of their careers is crucial for continued scientific progress," said Science's Editor-in-Chief Donald Kennedy. "We're delighted and honored to celebrate the achievements of this year's winners. Their workconducted in laboratories all over the worldwill help pave the way for advances to benefit society and to enhance our fundamental knowledge of the living world."
Schultz applauded Wang's persistence and ingenuity: "Although his work built on that of many others in and outside of our laboratory, it was Lei's creativity, experimental ability, and determination that cracked this incredibly challenging problem."
In addition to the annual Grand Prize Winner, a judging panel may present regional awards of $5,000 each to researchers within four geographic regions: North America, Europe, Japan and All Other Countries. The following five scientists were named to receive regional prizes in 2003:
Cell Behavior and Disease Development:
Albert Einstein (1879-1955) once said that "everything should be as simple as it is, but not simpler." In the past, prevailing views on single-cell gene expression were indeed simple: Cells, under the same conditions, were believed to generally behave alike. Scrutiny of the single cell is essential for better understanding of diseases such as cancer, explained Jeffrey M. Levsky, who was born in 1978 in Washington, DC. But, previous methods used samples containing millions of cells to determine the state of the average cell. Levsky's team used digital microscopy to detect many different sites of transcription all at once within individual cells. Computer image interpretation and mathematical algorithms were used to pinpoint gene-expression relationships. Levsky, of the Albert Einstein College of Medicine at Yeshiva University in New York City, discovered a degree of variability much greater than anyone ever imagined. "There may be every variation possible, from no genes expressed, to all at once, and every combination in between," he wrote. The research, with Robert H. Singer, is a step toward deeper knowledge of cell behavior and disease development.
What Gives Bacteria Their Shape?:
"I acquired a large variety of genetic, biochemical and cytological techniques and, most importantly, I discovered the beauty hidden in bacteria," Rut Carballido-López said of her award-winning research. A native of Barcelona, Spain, Carballido-López wanted to learn what gives bacterial cells their shape. Eukaryotes, with genetic material enclosed by a cell nucleus, have a cytoskeleton to define their silhouette. But, most cell biology textbooks have traditionally reported that the primitive prokaryotic cellsincluding bacteriadiffer fundamentally from the cells of higher organisms and lack a cytoskeleton. Carballido-López's Ph.D. research, guided by Jeff Errington at Oxford University, U.K., overturned this long-standing dogma by demonstrating that bacteria contain cytoskeletal elements that are structurally and functionally similar to eukaryotic actin. Using powerful microscopy techniques, she performed analyzed the living or "in vivo" properties of the actin-like Mbl protein of the rod-shaped bacterium, Bacillus subtilis. These findings led to a new model for bacterial growth and structure. Today, Carballido-López is a Human Frontiers postdoctoral Fellow at the I.N.R.A. of Jouy-en-Josas, France.
Understanding Gene Functions:
Ravi S. Kamath, from Overland Park, Kansas, has been studying molecular biology since he was first introduced to the field at the age of 13, when he worked in the laboratory of Joan Hunt at the University of Kansas Medical Center. Kamath's winning research, conducted with Julie Ahringer at the Wellcome Trust / Cancer Research UK Institute and the University of Cambridge, sheds light on how genes determine the properties of an organism. Kamath, now completing a medical degree at Harvard, studied gene function on a large scale by systematically "knocking out" almost all of the gene products in the nematode C. elegans for the first time. His work also has shown how gene functions have been determined and conserved through evolution, and how they are organized in the genome. His methods are helping to speed the discovery of genes involved in a wide range of biological processes.
ALL OTHER COUNTRIES:
Environmental Triggers and Adaptive Responses:
The quest for scientific discovery carried prize winner Qing Chen on a journey around the world, from her hometown of Jinan, China, where she was born in 1964; to Israel and the United States. Today, she studies the genomic features that make certain bacterial strains so dangerous, as part of her work for the Walter Reed Army Institute of Research in Silver Spring, Maryland. Her goal is to someday help develop new vaccines to improve public health. Chen's PhD research at The Hebrew University, guided by Orna Amster-Choder, looked at how cells process environmental information to generate appropriate adaptive responses. A model system, based on expression of the gene, bgl, within a bacterial host, E. coli, allowed her to pinpoint the specific site (Cys-24) within a Bgl sensor that serves as a molecular on-off switch for the gene. Depending on the protein stimulation, she found, Cys-24 binds either to a phosphoryl group or to another cysteine. Her findings suggest that other cellular processes, including signal transduction and transport, may be regulated in a similar fashion.
ALL OTHER COUNTRIES:
Oxygen Deprivation Responses:
How do cells cope with periods of oxygen shortage or "hypoxia?" David Lando was working at the University of Adelaide, Australia, with Murray L. Whitelaw when he discovered a second "switch" that helps mammalian cells respond to hypoxia. HIF (hypoxia-inducible factor) helps cells respond to oxygen deprivation, by triggering increased transcription of genes that boost oxygen intake. Scientists had known that a process called proline hydroxylation acts as a switch to keep HIF in check when oxygen conditions are normal. Lando showed that a second switch, asparagine hydroxylation, also regulates HIF responses. His winning essay, "The Huff and Puff of HIF Regulation," follows up on his publication in Science (1 February 2002). Lando now works at The Wellcome Trust / Cancer Research UK Institute.
23 October 2003