Research Revolution at Yale
November 23, 2009
By early next year, employees from three new core facilities are scheduled to complete their move to Yales's West Campus, a 136-acre property which features state-of-the-art laboratories and the latest in life science technology.
At the center of the sprawling 136-acre West Campus are three buildings that will house scientists who are using three distinct technologies yet who share an underlying mission: transforming the way biological research is conducted at Yale.
"New technologies are creating an unprecedented amount of data and providing entirely novel ways to address scientific questions," says Michael Donoghue, VP for West Campus planning and program development. "The new cores opening up on the West Campus put Yale in a unique position to capitalize on these advances to answer some of the most fundamental questions in biology."
By January, the three core facilities—-occupants of the largest acquisition in Yale's history—-will be open and assisting scientists in the business of discovery.
Already, the technologies employed by the Yale Center for Genome Analysis, the Center for High Throughput Cell Biology and the Small Molecule Discovery Center have proved to be invaluable in dozens of Yale projects—such as shedding light on the genetic basis of autism, tracking key molecular pathways in inflammatory diseases, and discovering a new cancer drug. The new cores will only increase the computational firepower of bioinformatics systems and allow Yale scientists to conduct experiments that would not have been feasible just a few years ago.
These core facilities will help support the entire university, but will also be linked closely to five new institutes planned for West Campus. The institutes will be in microbial biology, chemical biology, cancer biology, systems biology and cell biology.
Shrikant Mane is representative of the directors charged with day-to-day operation of the new facilities. All are scientists whose love of research led them to learn the diverse and powerful new technologies that are quickening the pace of discovery in the life sciences. All are silent partners in labs throughout the university.
As a collaborator on several grants, Mane has provided the biotechnological support for projects that seek the genetic basis of autism and age-related macular degeneration; help test novel ways to repair the central nervous system; explore genes crucial to the evolution of the human brain; and look for genes involved in asthma, schizophrenia, bipolar disease, kidney disease and brain aneurysms.
A recent collaboration between Mane and Richard Lifton, chair of Yale's Dept. of Genetics, illustrates the power of the new technology and provides a glimpse of its potential clinical value. For the first time they made a clinical diagnosis using comprehensive DNA sequencing of all the protein-coding genes in the genome. The technology, which selectively analyzes the 1% of the genome that encodes for proteins, allowed the scientists to pinpoint mutations in the genes of a five-month-old Turkish boy that cause congenital chloride diarrhea, a rare birth disorder in which the gastrointestinal tract fails to properly absorb chloride and water.
For now, Mane says he plans to harness the power of 12 sequencers at West Campus to aid the work of Yale researchers. "We have no doubt that one day the technologies that are being employed at the new West Campus facility will pave the way for personalized medicine by providing critical insights into identification of genetic risk factors, diagnosis, prevention and treatment for a host of human diseases," Mane says.
While Lifton, Mane and others are pushing the limits of genomics technology, James Rothman, chair of the Department of Cell Biology, recently has his own vision for the Center for High Throughput Cell Biology. Rothman, one of the top cell biologists in the world who was recruited to Yale last year from Columbia Univ., wanted to create a center that married several distinct technologies that together would give scientists an unprecedented view of the inner workings of the cell.
In the summer of 2008 the center became the first of the three West Campus cores to open for business. Rothman recruited Columbia colleague Lars Branden to become director of the core. The facility, which employs 13 people, helps researchers assess how genes function in a cell by selectively silencing genes in highly automated, genome-wide screens. The latest in optical microscopes assess the effects of gene expression in living cells and the deluge of data is fed into banks of computers. The bioinformatics system helps researchers develop a picture of how those genes interact in living cells.
"We can do this for any field of biology you can imagine,'' Branden says. "We want to be a hub of the Yale community's efforts to decipher complex biological processes."
While most of the individual and robotic technologies housed at the center have existed for years, Rothman envisions marrying the technologies in a way that will create something entirely new.
"The marriage of genomic, optical and bioinformatics screening technologies can shave years off research time as well as give scientists new insights into cell biology that will drive research forward," Rothman says.
By contrast, chemical screening is a well-developed technology that has been a key part of the drug discovery process for years. But it is rare for Univ. scientists to have easy access to such technology, says Janie Merkel, who runs the Yale Small Molecule Discovery Center, scheduled to open on West Campus in late November.
Using high throughput experiments capable of analyzing tens of thousands of possible future drugs a day, the five-person team at the center is in the business of looking for small molecules that affect many biological processes such as inducing or repressing the expression of genes, inhibiting the interactions of proteins or the activities of enzymes. In terms of medicine, this could mean using a chemical at the DNA, RNA or protein level to correct the behavior of diseased cells to simulate health.
The great potential of the technology for academic researchers was illustrated by the recent sale of the biotechnology company Proteolix, developer of a drug to combat multiple myeloma, to Onyx Pharmaceuticals in a deal potentially worth $851 million. The basis for the new drug, now in Phase II clinical trials, originated in the lab of Craig Crews, executive director of the Small Molecule Discovery Center.
Source: Yale Univ.
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