Washington D.C.- Victor Velculescu, a 29-year old cancer researcher at the Johns Hopkins Oncology Center in Baltimore, is the grand prize winner of a prestigious science award for his enterprising work on a technique that provides a "snapshot" of all the active genes inside a cell. This method promises to be a boon for scientists worldwide searching for cures to cancer and other diseases. On the eve of the completion of the Human Genome Project, Velculescu's work anticipates the next millennium's scientific challenge--to discover the function of the thousands of genes in the human body that will be sequenced in this global effort. His winning essay will appear in the 19 November issue of Science.
Amersham Pharmacia Biotech, a leading biotechniques company, and Science established the Young Scientists Prize together in 1995 to provide support to molecular biology scientists at the beginning of their careers. The judging panel may present awards in four different geographical areas (North America, Europe, Japan, and all other countries). The regional winners each receive $5,000; the grand prize winner is selected from the pool of regional winners and receives $25,000. Velculescu will be honored together with four other regional winners on 9 December at Uppsala University in Sweden, in a ceremony that coincides with the Nobel Prize festivities.
For his thesis, Velculescu developed a method known as SAGE (serial analysis of gene expression) that allows scientists to rapidly analyze the overall pattern of genes expressed in a cell. There are approximately 100,000 genes in the human genome, but only a fraction of them are expressed or "turned on" in a given type of cell.
"For a long time researchers have wanted to have a sense of which genes are active in which cells, which is what SAGE tells us," Velculescu said. "My particular interest is in how this technique could be applied to look at genes in human disease, such as what kinds of genes might serve as disease markers, which genes might be involved in the disease process, and so on."
The technique works by identifying a unique marker or tag of nucleotides (the building blocks of DNA) in a gene's transcript, which is the molecule that is produced when a gene begins to copy itself--a sign of gene expression. These molecular tags are then spliced together to form one long DNA molecule. By sequencing this long DNA strand, researchers can analyze multiple gene expressions all at once. This type of analysis is akin to serial processing in computers, where information is transmitted and dealt with as a continuous stream of data.
Researchers can use this method to develop a quick snapshot of all the active genes in a cell, or potentially throughout the entire genome, all at once. Velculescu coined the term "transcriptome" to describe an organism's total pattern of gene expression. Unlike the genome, which basically remains the same throughout an organism's life, the transcriptome is a dynamic entity, since gene activity changes in response to both external and internal conditions.
The SAGE technique was born out of Velculescu's quest to obtain a better insight into the genetics of human cancer. Scientists have an inkling of how a few cases of gene expression relate to certain kinds of cancer, but lack an overall picture of gene activity in cancer cells. For instance, Velculescu said that SAGE could be used to profile the total gene expression in both tumor and normal cells, so that researchers could compare the two and decide whether changes in gene expression might be responsible for a cancer's progression. The method could also be used to search for potential tumor markers in patient sera or in body fluids close to a particular cancer, or to look at genes that are expressed "downstream" from other important cancer genes, like oncogenes or tumor suppressors. "It's possible that we could use these observations to then see if we could deactivate or reactivate the specific gene," said Velculescu.
The process is generating a slew of satisfied scientists--a testament to Velculescu's success. 400 - 500 detailed protocols of the SAGE method have been delivered worldwide, with tens of SAGE-related papers already published. An overbooked conference last February in the Netherlands demonstrated the impressive range of SAGE applications. Researchers are using the technique to pinpoint disease factors, to model the genomes of whole organisms like yeast and worms, and to take a closer look at human tissues that have traditionally been difficult to characterize. There is another SAGE conference in the United States scheduled in 2000.
Velculescu was born in Romania, and moved to California with his family in 1977. His interest in the sciences is lifelong, beginning with a "fascination" with chemistry and astronomy at a young age. In high school he worked for Rockwell Science Center on a project involving superconductors, and at Stanford University he became interested in biology and biochemistry. He enrolled in a joint M.D./Ph.D. program at Johns Hopkins, channeling his efforts into understanding disease at the molecular level. "My medical training has been extraordinarily useful for understanding the key questions in human biology, which could help solve some of the problems that cause human suffering," said Velculescu.
A newlywed, Velculescu and his wife enjoy their free time hiking, skiing, playing tennis, and attending the theater and symphony. Velculescu also moonlighted as a keyboard player for a band called Wild Type, made up entirely of cancer researchers. "I'm semi-retired," he joked. "I didn't want to compete with my mentor Bert Vogelstein, who also plays the keyboards."
He intends to continue his research in genetics and human disease, but plans for the grand prize money are still up in the air. "It's quite a bit of money, and I'm still not used to thinking in those terms," Velculescu said. "I'll probably give some to charity. Oh, and maybe pay off some honeymoon debts."
"Victor epitomizes the young scientist that we know will be at the cutting edge of science in the next millennium. Support and recognition for their achievements is essential for the continued discovery of new drugs and therapies," said Ron Long, chief executive of Amersham Pharmacia Biotech.
Applicants for the Amersham Pharmacia Biotech & Science Young Scientists Prize earned their Ph.D. in 1998 and submitted a 1,000-word essay based on their dissertations. They were judged on the quality of their research and their ability to articulate how their work contributes to the field of molecular biology, which investigates biological processes in terms of the physical and chemical properties of molecules in a cell.
"Science is proud to take part in recognizing this cutting-edge research, and would like to congratulate all of this year's winners on their outstanding contributions to molecular biology," said Floyd Bloom, Editor-in-Chief of Science.
The four $5,000 regional winners are:
Lisa Goodrich, USA region: Goodrich has identified a gene in mice that may lead to the development of drugs to treat certain birth defects and a common form of skin cancer, basal cell carcinoma. This gene, known as patched, plays a crucial role in a growth and development pathway, and was previously only known in the fruit fly. patched mutations in humans can cause birth defects, skin cancer, and brain tumors. Its discovery in mammals adds to the growing body of evidence that cancer is caused by normal developmental systems going haywire. Goodrich received her Ph.D. from Stanford University, and is currently at the University of California at San Francisco.
Toshimasa Yamauchi, Japan region: Yamauchi looked at how cells receive information from outside their cell membrane via substances such as hormones and other protein messengers. His analysis may highlight some of the cellular mechanics of diseases like cancer. In his study, he uncovered a novel "cross-talk" connection between two of these different cell communication pathways. He is currently at the University of Tokyo where he also received his Ph.D.
Marilia Cascalho, Europe region (Portugal): Cascalho's work shows that mutations and DNA repair may work hand in hand when it comes to improving our immune system's "memory", or its ability to recognize and fight off invading pathogens. These two seemingly contradictory processes may also be involved in tumor growth, which could give her research clinical applications for treating certain cancers. Her study of immunoglobin gene mutation suggests that the high rate of mutation in these genes, which constantly adds to the body's repertoire of antibodies, is actually promoted by DNA repair mechanisms. Currently at the Mayo Clinic, she received her Ph.D. from the University of Lisbon, Portugal.
Giles Hardingham, Europe region (UK): Hardingham analyzed the different ways that calcium ions are involved in relaying and storing long-term information (like the memory of an important day or a never-forget skill like riding a bike) in the brain. His work could pave the way towards the development of drugs that aid failing memory or treat certain neurological disorders. His work looks at calcium flows into nerve cells following electrical brain activity, and how this activates the different chemical pathways that jump-start the genes underlying the memory process. Currently at the Medical Research Council in Cambridge, he received his Ph.D. from Cambridge University.
Science is a leading international journal that covers all scientific disciplines. It is published by the American Association for the Advancement of Science (AAAS), the world's largest general science organization. Science has the largest paid circulation of any peer-reviewed general science journal in the world, reaching a global audience of more than 143,000 individual scientists, engineers, and others with an interest in science and technology.
Amersham Pharmacia Biotech is at the frontier of new healthcare, providing the technologies to discover, develop, and deliver therapies faster and more cost-effectively than ever before. Owned 55% by Nycomed Amersham plc and 45% by Pharmacia & Upjohn Inc., it is an international market leader in most of its markets. Its innovative systems are used to sequence genes, uncover the structure and function of genes and proteins, separate biomolecules, screen potential drugs, and manufacture biopharmaceuticals.
Information about the prize and copies of the winning essays will be posted on Science Online (http://www.sciencemag.org/feature/data/pharmacia/1999.shl) and will be available on 18 November. Further information is also available from Amersham Pharmacia Biotech's press office. Please contact: Alexander Watson or Laetitia Mowat at Grayling, London at 44-171-255-1100.
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