The ChemGen IGERT Program (2005 – 2010)
Beginning in 2005, the Center for Plant Cell Biology provided graduate student training in interdisciplinary science through its ChemGen IGERT (Integrative Graduate Education and Research Trainee) program. Sponsored by the National Science Foundation and founded by leading practitioners of chemical genomics, this program trained 23 Ph.D. students versed in cell biology, chemistry, computational sciences and engineering, in advanced chemical genomics. Spearheaded by IGERT and CEPCEB Director Julia Bailey-Serres, with the participation of Plant Cell Biology Professor Natasha Raikhel, Chemistry Professor Michael Pirrung, Computer Science Professor Tao Jiang, and Biochemical Engineering Professor Jerome Schultz, this program trained graduate students to become adept practitioners in the field of chemical genomics and address fundamental biological mechanisms with broad relevance from biotechnology to human health.
A New Approach to Study the Functions of Genes and Biological Pathways
The completion of the genomic sequences of many organisms has created a vast resource of information as well as a vast challenge in understanding how all genes function within the cellular network. Traditional genetic techniques to study gene function involve deleting the gene, or perhaps destabilizing the mRNA that comes from it, and observing biological changes. These methods are limited in their ability to make changes in a temporal and spatial manner. As a result, some questions of gene function may not be easily addressed because of problems with lethality, for example. The presence of genes with redundant function in some organisms also compromises the traditional genetic approach. The field of chemical genomics arose from the realization that chemical compounds can be used to study the fundamental biology of cells through their effects on genes and gene products. For example, the powerful combination of genetic resources in the model plant Arabidopsis and advances in combinatorial chemistry provides an unprecedented opportunity to understand fundamental aspects of plant development and cellular processes.
Aim of Chemical Genomics
One outcome of a chemical genomics approach would be the identification and use of a chemical that can penetrate cells, is stable within them, and can act very specifically on a single gene product or on a particular pathway. The chemical target can be one or several proteins in the pathway. The requirement for cell penetration is best met with compounds of molecular weight less than ca. 700. The ideal outcome of chemical genomics is “a small molecule to modulate the activity of each known protein.” Because there are so many proteins (tens of thousands) within a cell, success depends on the availability and testing of large numbers of compounds. Chemical genomics has thus been enabled by combinatorial chemical techniques, which permit the rapid preparation of large numbers of chemical candidates and methods for rapid biological testing, so-called high-throughput screening.
The ChemMine Database
ChemMine is a compound mining database that facilitates drug and agrochemical discovery and chemical genomics screens. The associated publication is available in Plant Physiol: 138, 573-577. The ChemMine project is divided into three main components: a compound database, a cheminformatic toolbox and a screening database.