2008 Lasker Awards announced
Three researchers, linkurl:Victor Ambros,;http://www.umassmed.edu/faculty/show.cfm?faculty=1266 at the University of Massachusetts Medical School, linkurl:Gary Ruvkun,;http://www.hms.harvard.edu/dms/bbs/fac/ruvkun.html at Massachusetts General Hospital, and linkurl:David Baulcombe,;http://www.plantsci.cam.ac.uk/research/davidbaulcombe.
Three researchers, linkurl:Victor Ambros,;http://www.umassmed.edu/faculty/show.cfm?faculty=1266 at the University of Massachusetts Medical School, linkurl:Gary Ruvkun,;http://www.hms.harvard.edu/dms/bbs/fac/ruvkun.html at Massachusetts General Hospital, and linkurl:David Baulcombe,;http://www.plantsci.cam.ac.uk/research/davidbaulcombe.html at the University of Cambridge in the UK, will share the 2008 Albert Lasker Award for Basic Medical Research for their discovery of microRNAs, the Albert and Mary Lasker Foundation linkurl:announced;http://www.laskerfoundation.org/awards/currentwinners.htm today (Saturday, September 13).
Ambros and Ruvkun will receive the award for their work describing microRNAs in Caenorhabditis elegans. Baulcombe wins the award for his work in plants.
The Lasker-Debakey Award for Clinical Medical Research will be given to Akira Endo, a researcher at Biopharm Research Laboratories in Tokyo for his discovery of LDL-cholesterol-lowering statins.
And the biennial Lasker-Koshland Award for Special Achievement in Medical Science will be awarded to linkurl:Stanley Falkow,;http://cmgm.stanford.edu/micro/fac/falkow.html at Stanford University, for his work in microbes and host-pathogen interactions.
"The 2008 Awards represent science at its best: intelligent, creative and dedicated research that touches and improves the lives of people," Maria Freire, president of the Lasker Foundation, wrote to The Scientist in an Email. This year's awards underscore "the global nature of medical research, with discoveries in Japan, England, and the U.S."
MicroRNAs, tiny pieces of RNA as little as 21 nucleotides long, have been shown to play a big role in gene expression. "We are finding explanations for mechanisms of disease that no body could explain for years, like cancer and Alzheimer's," linkurl:George Calin,;http://www.mdanderson.org/departments/expther/display.cfm?id=7bed03e2-3c4d-4d10-8b1e9d5fcfcd22a9&method=displayfull&pn=bcf512c7-24ba-464c-b62521340eec2781 from MD Anderson Cancer Center, told The Scientist. "A lot of papers are telling us that microRNAs are involved in regions in cancer, expressed in schizophrenia, involved in diabetes. These discoveries have a huge impact."
The discovery of microRNAs began with developmental studies in the model organism C elegans. In the early 1980s, Ambros, a molecular biologist, was studying the role of a gene called lin-4 that had been associated with early developmental timing in the worm. Another gene -- lin-14 -- appeared to regulate later events in development, and Ambros linkurl:showed that lin-4 activity dampens lin-14 activity,;http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Search&term=Genes%20Dev.%5Bta%5D%20AND%201%5Bvol%5D%20AND%20398%5Bpage%5D&doptcmdl=Abstract maintaining the worm's proper developmental timing. Meanwhile, Ruvkun was examining lin-4's effect on lin-14. Somehow, it seemed, lin-4 was linkurl:altering lin-14 protein expression;http://www.ncbi.nlm.nih.gov/pubmed/1916264?ordinalpos=103&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum via a region on the lin-14 gene called the 3' untranslated region (3'UTR).
For decades, researchers had believed that only proteins could control gene expression. So as Ambros continued working on lin-4, trying to isolate the gene itself, he assumed he was looking for a DNA sequence coding for a protein. But unable to locate such a DNA sequence, his group started to consider that they might be looking for RNA. Finally, in the early 1990s, they found a piece of RNA --only 22 nucleotides long -- that they determined was lin-4. When Ambros and Ruvkun compared their data, the two researchers were surprised to find that the small lin-4 RNA matched sequences in Ruvkun's lin-14 3'UTR messenger RNA. suggesting that the linkurl:lin-4 RNA piece was acting directly on lin-14's 3'UTR.;http://www.ncbi.nlm.nih.gov/pubmed/8252621?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedarticles&logdbfrom=pubmed While other researchers were working on RNA interference, lin-4 was the first example of such a small fragment of RNA regulating gene expression.
Researchers assumed that the small RNA Ambros and Ruvkun observed was unique to C elegans. But during the same period, Baulcombe had been studying plant-virus interactions and the gene silencing phenomenon that had been previously observed when viral genes are introduced to the plant genome. Baulcombe reasoned that researchers had been unable to identify the factors responsible for gene silencing because they were very small. He identified small RNAs about 25 nucleotides long that were only present when certain plant genes were shut off. Baulcombe's linkurl:paper in 1999;http://www.ncbi.nlm.nih.gov/pubmed/10542148?ordinalpos=72&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum on the small sequence "was a real stimulus" to acceptance of the idea of small RNAs, Ambros told The Scientist, because it showed small RNAs weren't a worm-specific mechanism.
In 2000, linkurl:Ruvkun pinpointed;http://www.ncbi.nlm.nih.gov/pubmed/10706289?ordinalpos=65&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum the second small RNA in C elegans called let-7. And in 2001, linkurl:Ambros identified;http://www.ncbi.nlm.nih.gov/pubmed/11679672?ordinalpos=27&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum nearly 100 more small RNA's in flies, humans, and worms. "One of the important things in my mind about discoveries being recognized by these awards is that none of us were looking for what we found," said Ambros. "There wasn't a theoretical prediction before us that there should be another kind of regulatory molecule."
That new kind of regulatory molecule, called microRNA, changed the landscape of cell biology and many biological areas. After Baulcombe's paper, "it became clear that the audience for microRNAs was going to be humongously large," Ruvkun told The Scientist. Recent studies have found upward of 1000 microRNAs at work in everything from neurotransmission to oncology.
These discoveries have likely affected our view of the genome, as well. "In the old days proteins were considered to be the workhorse of cell," linkurl:Bino John,;http://www.johnlab.org/ a researcher at the University of Pittsburgh School of Medicine, told The Scientist. But "only 3% of whole human genome codes for proteins. That other 97% was in the old days considered to be junk DNA. And now with this understanding of microRNA, the whole field of how we view what a gene is and how many genes there are in human genome, that is just profoundly changing."
"It's really cool, the continual surprises that come out of [this research]," said Ambros. "We'll never cease to be astonished by microRNAs-- they're so much fun. They keep cropping up doing interesting and peculiar things. And this brings us into a lot of different kinds of biology."
The Lasker-Debakey Award for Clinical Medical Research this year honors Akira Endo's discovery that statins control LDL-cholesterol levels. Over decades of work, Endo searched through thousands of natural products to isolate which ones might block a key enzyme in the synthesis pathway of the harmful type of cholesterol. His work led to the development of the first statin approved for the clinic, more than 20 years ago. "The discovery of the statins has revolutionized clinical practice helping and preventing heart disease around the world," Freire wrote. "Dr. Endo's systematic and focused quest for the cholesterol-reducing agent testifies to his inspiration, his tenacity and his unwavering commitment to help people fight this terrible problem."
The Lasker-Koshland Award for Special Achievement in Medical Science was awarded to Stanley Falkow, honoring his work in establishing a set of postulates for determining which genes in a pathogenic microorganism causes disease in the miroorganism's host.
This is often called virulence factor, and Falkow based the postulates on Robert Koch's postulates from the late 1800s which outlined how to isolate and grow pathogens in culture. Falkow, who spent 50 years studying how microbes invade their hosts, also showed that bacteria pass antibiotic resistance to each other on circular DNA. "One of the best parts about the Lasker-Koshland recognition is that it focuses on the recent excitement in cellular microbiology and how the study of the biology of pathogenicity is teaching us about our own biology," Falkow wrote to The Scientist in an Email. "Also, it permits the public to learn more about microbes as a constant human companion."
Ambros, Ruvkun, and Baulcombe will share a the award cash prize of $300,000, while to other two recipients will get $300,000 each. The awards will be presented to the laureates at a ceremony on September 26 in New York City.
September 15, 2008
Baulcombe missed out on the Nobel for the same work.\nGood to see a great plant biologist get his due.
September 15, 2008
I think it's a real shame to have the discoverer of statins awarded a price! The people who voted for are either unaware of (unlikely) or totally ignoring the serious adverse effects. I am not referring only to Lipobay (although that is more likely to ring a bell to many people's minds)!\n\nAny biochemist in his(her) right mind would wonder how can you inhibit such an important enzyme like HMG-CoA Reductase and hope to get away with it. If you don't understand what I am talking, have a look at the Boehringer Mannheim metabolic pathways:\nhttp://www.expasy.ch/cgi-bin/show_image?D10&up\nFrom the top-left, go to mevalonate and "follow the lead", to the right, to geranyl-PP and farnesyl-PP (think about all ras-related proteins anchored in the cell membrane) and to tocopherol and ubiquinone (coenzyme Q10, needed to shuttle electrons between the mitochondrial complexes). It's not on paper only, have a look at peer-reviewed research based on FDA data:\nFDA adverse event reports on statin-associated rhabdomyolysis\nhttp://www.theannals.com/cgi/content/abstract/36/2/288\n\nHow can one develop a drug which stops the production of so many metabolically-important molecules and get a prize for it??