Dr. Inglese, a former scientist at Merck and Pharmacopeia, uses his previous experience in the drug development industry to inform the process of HTS at the NCGC. “By understanding the system’s limits, be it an assay design or screening process, one can innovate beyond them.”
Since the primary mission of the NCGC is to apply the tools of small molecule screening and discovery to the development of chemical probe research tools, demand has grown for screening technology innovations, library storage, delivery systems, and data interpretation to maximize the center’s data production efficiency. Dr. Inglese emphasizes that the center has a clear need to understand the impact of assay technologies on the chemical biology under study.
“In the course of developing assays as proxy measures for complex biological processes we often introduce new complexities related to the assay technique that must be appreciated during the interpretation of the screening results.
“We find that considerations of both the basic enzymology and cellular biology underlying the basis of the technology are critical to interpretation of the data based on reporter gene assays.”
For instance, discoveries based on the use of bioluminescent reporters have prompted further research into the depths of chemical biology for studies based on these systems. Thus, the broad-based chemical studies that are conducted at the NCGC have proven applicable to molecules that lie outside specific categories of interest.
The NCGC is also involved in training post-doctoral fellows in the use of the center’s technologies. Through the NCGC’s participation in the MLPCN, post-doctoral fellows can expand their previous education in basic research. The NCGC provides training on assay development technologies, screening and data analysis, and follow-up testing and chemical probe optimization. Post-doctoral fellows at the NCGC learn to collaborate with investigators in other academic, government, and private labs.
When matching post-doctoral fellows with project teams at the NCGC, Dr. Inglese says that they seek “scientists who wish to acquire the understanding and skills that will be useful in allowing them to become active in translational research, be that in the pharmaceutical industry, academia, or elsewhere.” He adds that the center is also looking for candidates who can work with an integrated, interdisciplinary team and demonstrate capabilities to master the highly technology-enabled processes in place at NCGC.
NIH post-doctoral fellows work with investigators to learn how to scale assays and acquire the means to interact with chemists to optimize compounds that have been discovered as potential drug candidates. According to Natasha Thorne, a current NIH post-doctoral fellow at NCGC, she has been offered the opportunity to work on projects that involve a broad spectrum of biological fields.
“Whereas my graduate student training largely involved independent research that delved deeply into a single, specific scientific question, my post-doctoral training at NCGC is multidisciplinary and involves establishing and maintaining collaborations with other scientists.”
Christopher Austin, M.D., director of the NCGC, is expanding the organization to include a focus on creating a pipeline of potential drugs for the treatment of rare diseases. In this regard, the NIH recently initiated a program to expand upon the work of NCGC and other screening centers’ work in the probe development pipeline.