New technology revolutionizing drug discovery

The National Science Foundation has awarded Weill Cornell Medical College researcher Dr. Scott Blanchard its prestigious Career Award, recognizing his groundbreaking work in cell biology -- work that is poised to revolutionize research for the next generation of young scientists.

The award totals more than $806,000 spread over five years.

Dr. Blanchard is a Strategic Plan recruit in the Department of Physiology and Biophysics and joined the college in 2004 as an assistant professor. He is perhaps best known for advancing fluorescence technologies that allow scientists to observe the activities of single-molecules in real-time. Much of his previous and ongoing research has been focused on the ribosome, the complex molecular machine responsible for translating DNA-encoded instructions into usable proteins.

"I'm extremely gratified to receive this award. It will help significantly to expand our work on the ribosome -- work that has potential for drug discovery. Nearly, half of all therapeutic agents target the ribosome. Nevertheless, we know precious little about how they affect this complex enzyme at the molecular level," Dr. Blanchard says. "The NSF award will shed important new light on conserved aspects of the ribosome mechanism across species, enhancing not only our basic knowledge how this enzyme is able to synthesize protein but also furthering our knowledge of how antibiotics work."

"This NSF award recognizes both Dr. Blanchard's important contribution to the field, as well as Weill Cornell's commitment to the kind of basic research that can yield real clinical breakthroughs," adds Dr. David P. Hajjar, senior executive vice dean and executive vice provost of Weill Cornell Medical College. Dr. Hajjar is also dean of Weill Cornell's Graduate School of Medical Sciences, the Frank H.T. Rhodes Distinguished Professor of Cardiovascular Biology and Genetics, professor of biochemistry, and professor of pathology and laboratory medicine at Weill Cornell Medical College and the Graduate School of Medical Sciences.

An NSF Career Award is typically designed to fund basic science and has a strong educational component, including the training of young scientists at the high school and undergraduate level.

"It's rare that the NSF bestows such an award upon a medical college, since these grants typically go to undergraduate institutions with a heavy emphasis on the basic sciences," adds Dr. Hajjar. "But Weill Cornell is strongly committed to supporting basic science with an eye to translational research -- bringing discoveries made in the lab up to the level where they can be used to solve clinically relevant problems. So, in bestowing this award, the NSF is also recognizing Weill Cornell as one of the elite basic-science training institutions in the nation."

Dr. Blanchard's work in fluorescence microscopy aims to revolutionize the way we examine how enzymes work.

"Until recently, scientists have been forced to observe the activity of enzymes en masse. This method measures only the average behavior of many billions of molecules present in a test tube, and is an expensive and relatively imprecise approach," Dr. Blanchard explains. "Or they rely on computational methods that animate static structural models. Single-molecule fluorescence microscopy aims to integrate these disparate views of enzyme function -- we actually watch photons of light coming out of a single molecule and use it to track a molecule's location, its interaction with other molecules, and tiny motions within the molecule itself. From these data, we hope to generate the first experimentally-validated movies of single molecules at work."

Since coming to Weill Cornell from Stanford University, Dr. Blanchard has focused his work on the ribosomal functions present in one of the most basic organisms on earth -- the E. coli bacterium.

"We looked first at E. coli because it has been exhaustively researched and its basic functions are relatively well understood. It was a proof-of-principle project that demonstrated that single-molecule fluorescence microscopy could illuminate ribosomal activity," the researcher explains.

But the most exciting research lies ahead.

"We know that the ribosome works by similar mechanisms across organisms and cell types. Yet subtle variations in function are evident in the effectiveness of ribosome-targeting antibiotics used clinically for the past 50 years," Dr. Blanchard says.

These antibiotics target -- and disrupt -bacterial ribosome functions, while leaving the human cell's ribosome alone. "We also suspect that the ribosomes of different human cell types work differently, depending on the organ or tissue in question," he adds. "Understanding and exploiting these differences may lead to opportunities for discovering highly targeted, safer and more effective medicines."

The fight against cancer is perhaps the greatest frontier for this avenue of research. "We have a pretty good idea that the ribosome functions inside cancer cells are markedly different from those inside healthy cells," Dr. Blanchard explains. "So, the ultimate goal here is to explore whether compounds like those used to target bacterial infection can be used to target only the cancer cell."

All of these breakthroughs are still years or even decades away, he cautions. But it's exciting stuff -- both for established researchers such as Dr. Blanchard and the next generation of up-and-coming scientists.

"In keeping with its educational focus, this new grant from the NSF will help fund the work of undergraduate students in our lab, as well as visits by local New York City high school students who are interested in the biological and physical sciences," Dr. Blanchard says. "In a recent visit to a local elementary school, I found that kids are incredibly informed and excited about the potential for basic-science discoveries to change all of our lives."

"We now have the tools in hand, and with the help of the NSF and others, I'm confident that great advances are waiting just over the horizon," he says.

Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in areas such as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, transplantation medicine, infectious disease, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease in an effort to unlock the mysteries of the human body in health and sickness. In its commitment to global health and education, the Medical College has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and most recently, the world's first successful use of deep brain stimulation to treat a minimally-conscious brain-injured patient.


The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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