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Tasha Nalywajko monitors one of the robotic instruments in the Vanderbilt Institute of Chemical Biology's new high-throughput screening facility. photo by Anne Rayner

Network to boost discovery efforts

BY: BILL SNYDER

6/17/2005 - Scientists at Vanderbilt University Medical Center have joined a major federal effort aimed at developing innovative chemical tools for drug discovery and biological research.

A high-throughput screening (HTS) facility, which opened recently within the Vanderbilt Institute of Chemical Biology, is one of nine pilot centers chosen this spring to participate in the Molecular Libraries Screening Centers Network (MLSCN), an initiative of the National Institutes of Health (NIH).

The Vanderbilt facility will receive a $2 million award from the NIH for the fiscal year beginning July 1. Nearly $89 million has been budgeted for the MLSCN centers over the next three years. After that, funding will continue for a smaller number of fully operational centers, federal officials said.

“We are very excited to have the opportunity to be a part of the first major public sector investment in high-throughput screening to support and accelerate basic and early drug discovery research,” said C. David Weaver, Ph.D., assistant director of the Vanderbilt Molecular Recognition and Screening Facility and research assistant professor of Pharmacology.

“Being chosen to participate in this effort helps to establish Vanderbilt in a leadership position in the application of HTS in an academic environment and offers an excellent opportunity for us to establish a broader base of collaboration in this challenging venture,” he said.

Weaver is co-principal investigator of the pilot screening center grant with P. Jeffrey Conn, Ph.D., professor of Pharmacology and director of the program in drug discovery at the Vanderbilt Institute of Chemical Biology.

Drug discovery research in the pharmaceuticals industry has led to the generation of massive “libraries” of small molecules — a class of organic chemicals that are the “active ingredients” in most drugs — and the ability to rapidly screen them for therapeutic or research potential.

However, “that potential was not being realized in the public sector because of a lack of infrastructure and resources and knowledge of the approach,” said Christopher P. Austin, M.D., senior advisor for translational research at the National Human Genome Research Institute.

The screening centers network is designed to extend the reach of new technologies and add to the researcher's “toolbox.”

“What we hope to do is take the assay, do the robotic screening on a big library, do some initial chemistry, and give (scientists) back a small molecule compound which allows them to query the function of that gene or pathway — to test a hypothesis,” Austin said in an interview.

“Although there will be many challenges in an undertaking of this scope and novelty,” Weaver added, “ultimately we believe the investment will pay off in a wealth of tools to help us increase our understanding of living systems and to support early drug discovery research.”

Getting on the network

The Molecular Libraries Screening Centers Network is included in a sweeping plan, called the “Roadmap,” which was developed by the NIH to accelerate the translation of basic science discoveries into tangible benefits for patients.

Part of that plan, called the Molecular Libraries and Imaging Roadmap, is supporting the research of nearly 200 scientists, including three at Vanderbilt:

• Conn, who also is director of the Program in Translational Neuropharmacology in the Department of Pharmacology, is using high-throughput screening to search for compounds that might improve treatment of Parkinson's disease and schizophrenia.

• James E. Crowe Jr., M.D., professor of Pediatrics and director of the Vanderbilt Alliance for Nanomedicine, is exploring the molecular and cellular basis of immunity with the help of nanotechnologies such as “quantum dots.”

• David W. Piston, Ph.D., professor of Molecular Physiology & Biophysics and director of the W.M. Keck Free-Electron Laser Center, is developing high-resolution fluorescent probes to image single molecules within living tissues and animals.

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