The evolving discipline of Chemical Biology (or Chemical Genomics) has empowered investigators with a new set of tools and approaches to probe basic biological and genetic questions. This strategy uses libraries of small molecules (e.g., natural compounds, aptamers, or the products of combinatorial chemistry) and high-throughput screening to advance understanding of biological pathways to identify compounds that act as positive or negative regulators of individual gene products, pathways or cellular phenotypes. In addition, the field of Developmental Therapeutics, long mainly pursued only within the context of pharmaceutical and biotechnology companies, is emerging within the academic sector, in large part due to the continued genetic division of diseases into subsets amenable to targeted therapies but that are too small from a market standpoint to attract the interest of for-profits. While this identification of small-market disease target groups is new and continuing, occurring in large part due to the human genome effort, the economic blocks to for-profits that have precluded the development of new therapies for """"""""orphan diseases"""""""" such as the pediatric malignancies, as well as """"""""Third World Diseases"""""""" like many of the infectious diseases, has been a longstanding problem. The liquid-handling robot and microplate reader that are the subject of this application are requested as part of a multi-institutional initiative, involving five institutions (St. Jude Children's Research Hospital, The University of Tennessee, Health Science Center, the National Center for Natural Products Research at the University of Mississippi, the University of Memphis, and Christian Brothers University) located in the Memphis, TN area, that seeks to establish robust Chemical Biology and Developmental Therapeutics programs to help address basic biological questions and to improve the therapy of disease, especially those diseases typically ignored by pharma and biotech. This initiative involves more than 20 investigators with varied areas of expertise, including molecular and cellular ontology, the infectious diseases, and medicinal chemistry, among others - most of whom have one or multiple NIH grants to support their studies, and are engaged in multi-disciplinary collaborative projects with one or more other investigators located at the five participating institutions. A component of this research initiative also includes the establishment of a high throughput screening (HTS) core facility to be based at St. Jude, which will be available to qualified investigators at all five local institutions to facilitate their efforts to develop small molecules for both basic research and possible therapeutic applications, especially for orphan disease targets. The liquid-handling robot and microplate reader requested in this application will help to meet the marked demand for HTS capabilities in the Memphis region - as is exemplified by the multiple investigator project descriptions that comprise this document - by helping to make a local HTS core facility a reality.
