NIH – Assay Development and Screening to Discover Therapeutic or Imaging Agents for Diseases of Interest to the NIDDK (R01)

July 22, 2016 by School of Medicine Webmaster


Projects submitted to this FOA should be directly focused on assay development and screening for a therapeutic or imaging agent that will modulate or track a health-related outcome of interest to the NIDDK. This includes outcomes relevant to obesity, diabetes, nutrition, and related aspects of endocrinology and metabolism; benign digestive and liver diseases; benign kidney, urological and hematologic disease; and specific aspects of cystic fibrosis. Additional information concerning programmatic areas at NIDDK is available Prior to submitting an application, investigators are strongly encouraged to contact the Scientific/Research Contact for this FOA to discuss the appropriateness of the proposed research to this FOA. Projects in areas that are primarily within the missions of other Institutes or Centers (ICs) of the NIH are not appropriate for this FOA and will not be supported. For example, research on diabetic retinopathy should be submitted to the NEI, research on cardiovascular disease, hypertension, or dyslipidemia should be submitted to the NHLBI, and research on cancers should be submitted to the NCI.

Staging of Therapeutics Discovery and Validation

The process of identifying and validating therapeutic leads or imaging agents such as small molecules or peptides for the treatment, diagnosis, or study of human disease begins with a hypothesis and can be viewed as progressing along a continuum of increasing confidence, leading to widespread acceptance of its use in people ( For the purposes of this FOA, these stages are defined as:

Identification of therapeutic or imaging leads: This may occur through a variety of approaches and stages such as developing an assay, screening compound libraries, or constructing prototype peptides with preliminary evidence that they may significantly impact or track a disease process.

Early-stage preclinical validation: Pre-clinical hypothesis testing to generate data that, over time, increases confidence that manipulation or monitoring of disease processes via a specific strategy may be clinically meaningful and safe. This process occurs prior to clinical testing of a new therapeutic or imaging agent, and ideally should include the use of human-derived data, tissues, cells, and systems.

Clinical validation: Studies conducted in human patient populations to fully understand the efficacy and safety profiles of a therapeutic or imaging agent. True validation of a therapeutic or imaging agent may take decades of post-regulatory approval data accumulation.

This FOA is intended to stimulate research that furthers the development of and/or screening with assays in order to identify therapeutic or imaging agents that may serve as 1) possible therapeutic or imaging agents or 2) the starting points for medicinal chemistry or protein engineering campaigns to develop such agents. It is NOT intended to support early-stage preclinical validation or clinical target validation. Later stage validation, discovery, and development efforts may be pursued via mechanisms outside of this FOA such as, but not limited to, spin-off companies, licensing to or partnering with pharmaceutical companies, other funding opportunity announcements, and non-profit organizations.

Examples of the type of assay development and screening projects that can be pursued under this funding opportunity include, but are not limited to:

  • Generating data that demonstrates a biologically-relevant phenotypic assay can be conducted at a scale sufficient to screen a meaningful library of molecules, including an appropriate statistical analysis of the assay’s rigor and reproducibility as well as technical and logistical feasibility;
  • Conducting a high- or medium-throughput screening campaign with a well validated assay against a well-characterized library (focused or large) of small molecules, macrocycles, or peptides, including appropriate follow-up validation and characterization of hits.
Research Goals and Objectives

This FOA advances basic research findings into therapeutic and imaging agent discovery by promoting the adaptation and implementation of state-of-the-art measures of basic cellular processes or molecular events that are key mediators of disease pathogenesis into novel assays with the intent to probe or modulate mechanisms or perturbations in an unbiased and efficient manner. Proposed projects may involve collaboration with an academic, nonprofit, or commercial screening facility that has the requisite expertise and experience to conduct a screening-ready assay for the discovery and validation of therapeutic or imaging agents. Assays are expected to target outcomes relevant to the NIDDK mission.

Suitable assays development projects include, but are not limited to:

  • Novel adaptation of assays to increase throughput or include high content, multiplexed measures that maximize the amount and value of the captured data;
  • Optimizing phenotypic assays for outcome measures relevant to disease pathophysiology such as monolayer assays, microfluidic assays such as engineered microphysiological systems, or self-organizing organotypic assays;
  • Novel adaptation of assays for imaging and quantifying dynamic changes in the localization of signaling molecules, intracellular compartmentalization, regulatory networks, or folding/sorting machinery;
  • Assays to identify highly specific molecular markers that might be useful for identifying or tracking a particular cell or phenotype;
  • Phenotypic, model organism-based assays (e.g., Drosophila, C. elegans, zebrafish), in particular projects that aim to significantly improve on the automation of imaging analysis and whole organism handling;
  • Development of screens for targeted phenotypes in cellular models derived from human patient populations (e.g., induced pluripotent stem cells, cadaveric donor cells, biopsy samples) to identify alterations in cellular processes associated with disease processes;
  • Novel target-focused in vitro or cell-based assays to modulate the activity of a target strongly implicated in a disease-relevant network.

For projects conducting a screen with an assay, suitable library types may include, but are not limited to:

  • Small focused collections (hundreds to tens of thousands) to large collections (hundreds of thousands to millions) of small molecules;
  • DNA barcoded macrocyclic chemical libraries;
  • Collections of fragment molecules that serve as starting points for medicinal chemistry;
  • Cheminformatics approaches utilizing virtual libraries of compounds;
  • Libraries based on peptides or metabolites (e.g., metabolic intermediates, microbiome-derived products, lipid derivatives).

The following are types of projects that are NOT appropriate for this FOA:

  • Research focused on understanding normal biology or disease processes, rather than developing the tools to facilitate such;
  • Projects that propose significant efforts in molecular optimization that do not directly follow a proposed screening campaign;
  • Projects in which the primary focus is assay development or screening without an integrated plan to evaluate the validity of the assay for a health-related outcome within the mission of the NIDDK;
  • Projects in areas that are primarily within the missions of other Institutes or Centers (ICs) of the NIH are not appropriate for this FOA and will not be supported. For example, research on diabetic retinopathy should be submitted to the NEI, research on cardiovascular disease, hypertension or dyslipidemia should be submitted to the NHLBI, and research on cancers should be submitted to the NCI.

Deadlines:  letters of intent are due 30 days before full proposals; standard dates apply


Filed Under: Funding Opportunities