The W.M. Keck Foundation of Los Angeles has awarded the University of Colorado at Boulder $1 million to bridge the gap between molecular and cellular structures, a project expected to lead to significant advances in biomedicine.
Spearheaded by Nobel Laureate and Professor Thomas Cech of the chemistry and biochemistry department and Professor Richard McIntosh of the molecular, cellular and developmental biology department, the $1 million grant was approved by the Keck Foundation in July. Participating faculty, researchers and students hope to create a new generation of research spanning the gap between atomic-resolution structures of biological macromolecules and images of cellular architecture.
"We thought the timing was right to try something that has never been done before," said Cech. "There has been a revolution occurring in structural biology for the past 20 years, and the success and advances have made researchers much more ambitious, encouraging them to take on extremely difficult problems that might have seemed foolish to attempt even 10 years ago."
Cech, also a Howard Hughes Medical Investigator, will become president of the Howard Hughes Medical Institute of Chevy Chase, Md., in January 2000. He plans to return to CU twice monthly to oversee his lab.
Some of the specific objectives of the Keck grant include determining the structure of telomerase, the chromosome-end enzyme implicated both in aging of human cells and cancer. Headed by chemistry and biochemistry Professor Steve Schultz, the telomerase structure project is extremely challenging, said Cech.
"It is difficult to obtain enough pure telomerase to try to grow crystals because telomerase is not very stable," Cech said. But I think we have a talented group of students who can help overcome this problem."
Another project, carried out under the direction of Assistant Professor Lin Chen of chemistry and biochemistry, will be to look at Interleukin聳2 gene expression at the structural biology level, said Cech. Interleukin-2 stimulates the immune system, including the point that certain white blood cells, known as helper T-cells, divide. As the first line of defense against immune system invaders, T-cells are activated by an antigen to produce antibodies.
This research has implications for patients with autoimmune disease who are producing inappropriate antibodies against their own cellular components, as well as patients needing to have their own immune response suppressed during organ transplants in order to allow foreign organs to successfully graft to tissues of patients, Cech said.
MCD biology Professor Richard McIntosh, who specializes in cell mitosis, believes the Keck-funded program may allow students and faculty to create a website in which users could "take a tiny car and motor through and around a cell in three dimensions," said Cech.
"All of these projects are very ambitious, but the time has come to tackle them," said Cech. The program will involve the use of electron microscopes, x-ray crystallography equipment, and other sophisticated instruments.
The W.M. Keck Foundation of Los Angeles is one of the nation's largest philanthropic organizations. Established in 1954 by the late William Myron Keck, founder of Superior Oil Co., the foundation's grants are focused primarily on breakthrough research in science, engineering and medicine.
"The Keck Foundation has been very supportive of CU," said Cech. "The foundation funds help us 聭jump-start聮 new programs and allow us to further develop them and pursue federal grants. A side benefit is that most of the Keck biology grants go to top-tier schools such as Yale, MIT and the University of California, San Francisco, indicating Keck believes our research at CU is of the highest quality."
The CU-Boulder team has already begun ordering equipment and selecting students to participate. Undergraduates will be provided with research supplies, while gradate students and post-doctoral students will receive stipends, said Cech.