The overarching goal of this funding opportunity announcement (FOA) for the Common Fund program “Illuminating the Druggable Genome” (IDG;https://commonfund.nih.gov/idg/ is to solicit applications to build a set of Cutting Edge Informatics Tools (CEITs) that will augment the capability of the IDG consortium’s Knowledge Management Center (KMC) as well as the broader IDG Consortium.
Awards will support the IDG Consortium by: (1) developing and deploying tools to enhance the community’s ability to process, analyze, and visualize IDG data, (2) prioritizing new data resources and methods to be incorporated into Pharos(https://pharos.nih.gov/idg/index)that will strengthen predictions about physiological and disease associations around IDG-eligible understudied proteins (non-olfactory GPCRs, protein kinases, and ion channels), and (3) developing methods to prioritize IDG-eligible understudied proteins for deeper study using experimental assays both developed within the IDG pipeline or by the larger community.
The IDG consortium’s purpose is to facilitate the unveiling of the functions of selected understudied proteins in the Druggable Genome using experimental and informatics approaches. Currently, this research consortium is composed of multiple Data and Resource Generation Centers (DRGCs), a Knowledge Management Center (KMC), and a Resource Dissemination and Outreach Center (RDOC).
The human genome has revealed a great deal about the human proteome, though significant portions remain understudied that could have implications in various diseases. Only a subset of expressed proteins demonstrates the requisite properties to serve as targets for the development of therapeutics. Many bona fide drug targets likely remain to be discovered in the Druggable Genome (DG), which can be defined as a subset of the ~20,000 genes in the human genome encoding proteins that have the potential to bind drug-like molecules. The term “drug-like” refers to the physical, biochemical, and pharmacological attributes of small molecule compounds that are generally recognized to be required for efficacious clinical drugs in humans. While the number of proteins in the DG is upwards of 3,000, the existing clinical pharmacopeia is represented by only a few hundred targets, leaving a huge swath of biology that remains unexploited.
The discovery of a disease association or the development of a useful tool reagent can accelerate research into a previous understudied protein. Many interesting and critical biological processes and potential therapeutic avenues remain unexplored because an initial, catalyzing event has not yet occurred. Thus, the IDG Program is addressing this issue by systematically querying these understudied proteins to find phenotypic associations and develop useful research tools that could potentially translate into new methods for treating diseases.
While at the informatics level, genome- and proteome-wide tools can collate information and query all proteins, technical feasibility necessitates a narrower focus of experimental efforts into protein families for which there are definable understudied members along with existing technologies that can be readily adapted at the scale necessary for wholesale elucidation of their function and generation of tools. During the Pilot Phase of the IDG, it was determined that the experimental focus of the IDG will be on the understudied members in the families of non-olfactory GPCRs, ion channels, and protein kinases, as these families contain adequate numbers of understudied members and are well-established druggable families with high potential to impact human health once disease associations are made.
The IDG Program inspires innovative research by revealing a number of new activities and potential drug targets amongst these understudied proteins. Moreover, it is anticipated that the IDG Program will enhance our understanding of on- and off-target effects by establishing functional relationships among understudied members of the commonly targeted IDG-eligible protein families.
Thus, the overall goal of the IDG Program is to catalyze research in areas of biology that are currently understudied but that have high potential to impact human health by:
- Identifying biochemical, cellular, or animal model phenotypes for understudied proteins from druggable gene families.
- Enabling further investigation of those proteins by providing reagents and tools.
- Generating, maintaining, and facilitating the use of a minable knowledge base.
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Filed Under: Funding Opportunities