Archive for October, 2010

BUFFALO, N.Y. — Twenty-first-century pharmaceutical breakthroughs require 21st-century drug discovery tools, such as computational or in silico molecular design and high-throughput screening of effective, new compounds. That’s the theme of a University at Buffalo symposium to be held Sept. 11 on “Twenty-first Century Bioscience: In Silico Methods and High-Throughput Screening,” which will feature a variety of cutting-edge advances in the field developed by researchers in Western New York and throughout the US.

The symposium will be held at the Hauptman-Woodward Medical Research Institute, 700 Ellicott St., Buffalo from 8:30 a.m. to 5 p.m.

Speakers will discuss techniques they are developing to treat cancer and other disorders, including such hereditary eye diseases as retinitis pigmentosa.

Symposium topics will range from using flow cytometry and combinatorial chemistry to screen new compounds, to overcoming the hurdles in RNA drug discovery and developing molecular regulators of gene expression.

Research into computational or in silico methods of designing potential new drug compounds and high throughput screening of them is especially strong in Western New York, according to Steven J. Fliesler, PhD (pronounced Fleece-ler), the Meyer H. Riwchun Endowed Chair Professor of Ophthalmology, and vice chair and director of research in the Department of Ophthalmology, Ross Eye Institute, in the UB School of Medicine and Biomedical Sciences. Fliesler is a health systems specialist at the Veterans Affairs Western New York Healthcare System; he organized the symposium and is one of the moderators.

“Western New York is fortunate to have a diversity of scientists working in these areas on specific applications to human disease,” Fliesler says. “So whether it’s in cancer, ophthalmology, cardiovascular disease or diabetes, these genetic approaches are going on in parallel, utilizing some of the same approaches but with diverse applications. The goal of this combination of methods is to give investigators more powerful tools with which to alter how the genome is expressed in cells and silence disease-causing genes.”

For example, Fliesler and his UB colleagues are conducting research on novel gene therapy applications to treat retinitis pigmentosa, a group of genetic eye conditions that can lead to incurable blindness and which Fliesler says underscores the importance of genomic research.

In retinitis pigmentosa, he says, there are well over a hundred known mutations in the gene that codes for the visual pigment rhodopsin alone, and there are dominant and recessive forms of the disease.

“If it was possible to just disable the disease-causing allele (one member of a pair of genes) early in development, then you’d get a normal individual,” Fliesler says.

Plenary lectures will be given by Larry A. Sklar, PhD, of the University of New Mexico, John S. Lazo, PhD, of the University of Pittsburgh, Bryan Roth, MD, PhD, of the University of North Carolina at Chapel Hill and Menghang Xia, PhD, of the National Institutes of Health.

Topics of other talks will include:

* Advances in genomic techniques that have allowed scientists to dissect how the cell responds to changes in the environment by modulating access to information encoded in the genome. The talk, by Michael J. Buck, PhD, UB assistant professor of biochemistry, will focus on a master regulator essential for cellular stress response and how it controls access to the genomic information.
* challenges in developing RNA drugs and ways that UB scientists and others are working to overcome them. Development of RNA drugs as novel gene-based therapies for retinitis pigmentosa and other retinal degenerations is a primary focus of the research program of Jack M. Sullivan, MD, PhD, UB associate professor of ophthalmology, who will discuss an experimental platform his group has developed to rapidly screen large sets of candidate RNA drugs to identify the most powerful treatments for retinitis pigmentosa and common age-related macular degeneration.
* A high-throughput functional genetic approach to anti-cancer drug targets developed by Andrei V. Gudkov, PhD, chair, Department of Cell Stress Biology at Roswell Park Cancer Institute.
* Computational methods developed by Rajendram V. Rajnarayanan, PhD, UB assistant professor of pharmacology and toxicology, who is using them to design small molecules that can alter RNA expression.

In addition to Fliesler, other moderators and speakers include Alexander N. Cartwright, PhD, interim vice president for research at UB, Norma J. Nowak, PhD, director of scientific planning at UB’s New York State Center of Excellence in Bioinformatics and Life Sciences, Eaton E. Lattman, PhD, chief executive officer of HWI and research professor in the UB Department of Structural Biology, and Jennifer A. Surtees, PhD, assistant professor of biochemistry at UB.

The symposium is sponsored by the UB 2020 Strategic Strength in Molecular Recognition in Biological Systems and Bioinformatics, a cross-disciplinary effort to foster new scientific ideas throughout different departments and schools at UB and its partner institutions. Co-sponsors are HWI, the UB departments of biochemistry and chemistry and the Ira G. Ross Eye Institute.

For more information and to register, contact Jennifer Hunt at jluck@buffalo.edu in the UB Department of Biochemistry.

The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB’s more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
Source: molecularstation.com

Book: Chapter 18 Handbook of Drug Screening, Second Edition
Ramakrishna Seethala and Litao Zhang
Cover Image

Published
June 2009
ISBN
9781420061697
Edition
Second
Pages
504
Size
6 x 9 in
Format
Hardcover
142 illustrations

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Chapter Opening

High throughput screening (HTS) has progressively evolved since the late 1980s as an important approach for new lead discovery and a chemistry starting point (1). The size of compound collections used in HTS campaigns has also increased significantly from under 100,000 to a few million in major pharmaceutical companies. In the 1990s, pooling approaches, in which 10 to 20 compounds were contained in one well, were widely used for compound screening due to the limited screening throughput (2). Frequent interference from compounds in pooled samples and time-consuming hit deconvolution from the primary screen impaired the ability of lead identification using early pooling strategies. In the late 1990s and early 2000s, single-compound screening became the main platform with the advances in HTS technology and increases in screening throughput. However, primary screening of compound collections is routinely performed at a single concentration, typically as a single replicate, due to the high cost and time requirement for screening such large compound collections (usually in millions of compounds). Screening at a single concentration provides only a limited window of opportunity to identify the useful lead compounds.
Source: informahealthcare.com