ARRA Investments in High Throughput Screening
Public Health Burden
Traditional approaches to drug discovery and development, which involved testing potential compounds one at a time, was costly and time consuming. High throughput screening (HTS) is an advanced technology that allows multiple experiments to be done at once, greatly facilitating the drug discovery process. HTS has the potential to directly reduce the public health burden from a large number of diseases including rare diseases.
HTS allows hundreds of thousands of different samples to be tested simultaneously for a given characteristic. Robots precisely measure experimental reagents and distribute them into thousands of tiny chambers in plastic dishes that are then placed under specific experimental conditions for set amounts of time. Because multiple experiments can be done at one time, the time and effort needed to discover genes or chemicals that have specific properties, such as the ability to prevent a virus from infecting a cell, is greatly improved. The chemicals identified through HTS may be precursors to new drugs for a variety of disorders such as cancer and heart disease. The success of the HTS approach depends on many factors, including the quality of the chemicals or genes that are screened for activity and the tests used in the screen. Following identification of chemicals with the desired activities, it is often worthwhile to perform some chemical reactions on them to make them more stable or potent. The following ARRA awards are focused on developing new tests and chemistry resources to use in HTS:
Developing tests to identify inhibitors of malaria parasites that can provide insights into the biology of this parasite and lead to new drugs.
Developing an HTS test that can screen three-dimensional cultures of human cancer cells to identify chemicals that kill cancer cells under conditions that mimic intact tissues instead of cells grown artificially in a flat Petri dish.
Establishing a collection of chemicals and a group of chemists to convert lead candidates into useful drugs in a broad range of disease areas.
HTS tests can reveal new tools for biomedical research, for example, by identifying chemicals that inhibit processes that are not well understood. Researchers can observe the changes that occur when the chemical is used to inhibit the process of interest and learn more about the process. ARRA funded grants are exploiting HTS to identify new research tools that may eventually lead to new drugs.
Identifying cellular genes that are necessary for Human Immunodeficiency Virus (HIV) to go into hiding or become dormant, with the goal of exploiting these genes to prolong HIV dormancy and reduce the symptoms of acquired immunodeficiency syndrome (AIDs).
Identifying chemicals that inhibit only a subset of the activities of a group of proteins commonly targeted by drugs, with the long-term goal of generating new drugs with fewer side effects.
Discovering chemicals that kill specific bacteria in the gut and can be used both as research tools and as leads for therapeutic agents.
-- A Cell-based HTS for delayed death inhibitors of the malarial parasite plastid -- Fidock, David (NY)
-- High throughput screening in human 3D spheroids of epithelial, endothelial and stromal cells -- Vuori, Kristiina (CA)
-- The Southwest Comprehensive Center for Drug Discovery and Development -- Hulme, Christopher; Meurice, Nathalie, (contact); Mousses, Spyro (CA)
-- Developing transmissible antivirals by exploiting gene-expression circuitry -- Weinberger, Leor (CA)
-- Selective modulation of GPCR signal transduction with biased ligands-- Lark, Michael William (PA)
-- Discovery of gut microbiota-targeted small molecules: new tools and therapeutics -- Sonnenberg, Justin
Page Last Updated on June 30, 2018
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