NIH/NIDDK – New Paradigms in Tissue Communication-from mediators to metabolic function (RC2 Clinical Trials Optional)

August 6, 2018 by School of Medicine Webmaster

The overall goal of this FOA is to support research that will identify and study new messengers and communication pathways within and between tissues that impact metabolic function and dysfunction.

Advances made should facilitate the development of better models of tissue systems for studying diseases, improved strategies for in vivo targeting of specific tissue compartments and tissue functions, and/or new classes of therapeutic molecules. In addition, it is anticipated that many of the studies supported under this initiative may include a systems biology framework as needed to integrate data and information about signaling crosstalk.  Data analysis will also likely need to go beyond standard statistical approaches and may require the development of new or novel computational models.

Research supported under this FOA should focus on human physiology and lead to discoveries with potential clinical implications, including the identification of: 1) new signaling paradigms controlling energy balance and the development of obesity, or glucose handling and diabetes pathogenesis; 2) new therapeutic targets for obesity, diabetes or diabetes complications; or 3) novel biomarkers for the detection of disease initiation, monitoring of disease progression, or recording the development of complications in Type 1 or Type 2 diabetes. While applications to this FOA may utilize animal models, the relevance of any new signaling discovered in a non-human system should be validated in human cells or tissues within the timeframe of the funding period.

Communication modes and contexts that may serve as areas of focus for study include:

  • Surfaceomes and juxtacrine signaling: molecular complexes and signaling pathways that mediate cell-cell communication by direct contact (ECM, integrins, lipids) or exchange of cytoplasmic content (tunneling nanotubes, exosomes, extracellular vesicles);
  • Functional niches and paracrine signaling within tissues and organs: signals generated within and between tissue subregions, or between adjacent tissues (lymphatic vessels, microvascular beds, interstitium, perivascular niches, or local neural networks), that influence metabolic function and dysfunction;
  • Long-range signals: factors produced by specific cell types or tissues that are released in the circulation that mediate or regulate organ crosstalk (peptides, RNAs, lipids, metabolites, vesicular cargos).

Examples of potential research topics within these focus areas include (but are not limited to):

  • Characterization of key signals from the microbiome that impact glucose handling and/or diabetes pathogenesis;
  • Communication within the interstitial space that may contribute to, or report on, early events in the development of diabetes and complications that affect multiple organ systems;
  • Exploration of novel bioactive peptide production, secretion, and sensing by the brain and peripheral tissues impacted by altered energy balance and/or in diabetes;
  • Use of synthetic biology to develop biosensors that can track and report on changes in local tissue environments or signaling milieu during the progression to diabetes and its effect on end organ tissues;
  • High-resolution characterization of tissue compartments and niches (e.g. to inform the building of next-generation human tissues or organoids on a chip for disease modeling and drug screening);
  • Primary cilia as signaling platforms for the control of energy metabolism;
  • Mechanotransduction signals that play a role in sensing and communicating the metabolic status of tissues and end organs (e.g. as mediators of physical activity and potential therapeutic targets).

Scope and Specific Requirements

Applications submitted to this FOA must focus on organs and tissues that contribute to metabolic dysfunction resulting in diabetes or obesity. The scope of this FOA includes, but is not limited to, the following:

  • Groundbreaking, innovative, high impact and cross-cutting research projects that will improve and accelerate biomedical research.
  • Basic, clinical and translational projects that could fundamentally enhance the research enterprise and that require the participation, interaction, coordination and integration of activities carried out in multiple research laboratories.
  • Creation of large scale unique resources and/or development of transformative technologies that can benefit a wide range of investigators.
  • High-impact discovery-based and hypothesis-generating science.

RC2 projects are not intended to support:

  • Traditional investigator-initiated, hypothesis-driven and highly focused studies (best supported by the R01 or P01 mechanisms).
  • Research that is a logical extension of ongoing work.
  • Core (or related) services to supplement the budgets of existing R01-type efforts.
  • Applications with a major emphasis outside of the mission of the NIDDK.

Prior Consultation with NIDDK

Consultation with NIDDK staff at least 3 months (and preferably 6 months) prior to the application due date (including resubmission applications) is strongly encouraged for submission of the High Impact, Interdisciplinary Science in NIDDK Research (RC2) application. If requested, NIDDK staff will consider whether the proposed RC2 meets the goals and mission of the Institute; whether it addresses one or more high priority research areas; and whether the application is best fit to the RC2 activity code.

NIDDK staff will not evaluate the technical and scientific merit of the proposed project; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA. During the consultation phase, if the proposed project does not meet NIDDK’s programmatic needs or is not appropriate for this FOA, applicants will be strongly encouraged to consider other Funding Opportunities.

Deadlines:  November 1, 2018; May 30, 2019; October 31, 2019; June 2, 2020; November 3, 2020; June 1, 2021 (letters of intent are due 6 weeks prior to the deadline)


Filed Under: Funding Opportunities