Howard P. Isermann Professor, Department of Chemical Engineering
Rensselaer Polytechnic Institute

Date: Thursday, January 11, 2007
Time: 11AM-12PM
Location: IBB 1128

"Molecular Bioprocessing as a New Paradigm for Drug Discovery"

Abstract: Using tools of systems, and more recently synthetic, biology the generation of biological diversity by engineering the biosynthetic gene assembly of metabolic pathways has led to a wide range of "unnatural" variants of natural products. However, current biosynthetic techniques do not allow the rapid manipulation of pathway components and are often fundamentally limited by the compatibility of new pathways, their gene expression, and the resulting biosynthetic products and pathway intermediates with cell growth and function. To overcome these limitations, we have developed an entirely in vitro approach to synthesize analogs of natural products in high throughput. In this talk I will highlight our recent efforts in developing such approaches to accelerate drug discovery and development. Specifically, we have brought together biocatalysis and human cell culture on high-throughput platforms for the generation of unique natural product analogs, including polyphenols and polyketides, with anti-inflammatory and anticancer biological activities. We have also developed a microarray platform for the identification of potential drug candidate toxicity. The so-called MetaChip (Metabolizing Enzyme Toxicology Assay Chip) enables the early-stage evaluation of drug candidate toxicity through combined high-throughput P450 catalysis and cell-based screening on a microscale platform. As a result of these high-throughput platforms, the pharmaceutical industry can make better educated decisions on which compounds to take forward out of discovery, which is expected to accelerate drug development times, and reduce investment in late-stage drug failures.