Internal Deadline: October 8, 2021, 5pm PT
LOI: November 21, 2021
External Deadline: December 21, 2021
Award Type: Cooperative Agreement
Estimated Number of Awards: NIDDK intends to commit $3,800,000 in FY 2022 to fund up to 7 awards.
Budget Info: Application budgets are limited to $375,000 direct costs per year.
Who May Serve as PI: Standard NIH requirements.
Process for Limited Submissions
PIs must submit their application as a Limited Submission through the Office of Research Application Portal: https://orif.usc.edu/oor-portal/.
Materials to submit include:
- (1) Single Page Proposal Summary (0.5” margins; single-spaced; font type: Arial, Helvetica, or Georgia typeface; font size: 11 pt). Page limit includes references and illustrations. Pages that exceed the 1-page limit will be excluded from review.
- (2) CV – (5 pages maximum)
Note: The portal requires information about the PIs and Co-PIs in addition to department and contact information, including the 10-digit USC ID#, Gender, and Ethnicity. Please have this material prepared before beginning this application.
This Funding Opportunity Announcement (FOA), together with the companion FOA, RFA DK-21-502, invites applications to renew the NIDDK IBDGC to address three main research objectives: 1) to further characterize the genetic architecture of IBD phenotypes within populations currently underrepresented in IBD genomic research, integrating genetic and environmental predictors in risk models; 2) to identify the causal genetic variants and the genes, proteins and pathways they act upon within susceptibility loci for IBD phenotypes; and 3) to elucidate the biological mechanisms by which risk-associated and protective variants influence the pathophysiology of IBD and its clinically important sub-phenotypes and outcomes. The long-range goal of the research to be carried out by the IBDGC is the enhancement of our understanding of the pathophysiologic mechanisms of IBD in order to improve patient outcomes.
Identification of causal variants and of the genes they act upon can be accomplished via fine-mapping techniques involving high-density genotyping and exome and whole genome sequencing in large numbers of subjects from populations of diverse ancestry, integration of other molecular and regulatory datasets measured in patient samples and/or available via public databases, and screening and functional testing of candidate variants in laboratory-based assays and model systems. The IBDGC is expected to continue to apply current versions of these approaches to characterize more of the previously identified IBD loci, with particular attention to representing genetic heterogeneity and diverse ancestries in all methodological approaches. The IBDGC may also draw on the rich clinical datasets available via electronic health record (EHR) databases and associated biobanks to expand and characterize the IBD phenome, incorporate pharmacogenomic analyses, and identify new important phenotypes for analysis. In view of the central (but yet to be fully elucidated) role of the intestinal microbiota in the pathophysiology of IBD, the IBDGC may also continue analyses of the composition and activity of the intestinal microbiome, and integrate these results with other environmental exposures and risk factors, and with host genetics. Systems biology approaches and longitudinal studies will be needed to integrate genetic and multi-omic datasets along with pharmacogenetic and environmental exposure data to create and refine risk models for multiple IBD phenotypes and clinical outcomes.
Functional screening of candidate genes and variants and biological perturbation studies in a variety of experimental systems may be required to identify causal variants and to elucidate the mechanisms by which they act to influence IBD pathophysiology. Functional and mechanistic studies may employ any of a wide variety of assay platforms and model systems (e.g., cultured cells, organoids, zebrafish, mice) to investigate function in physiological domains relevant to IBD (e.g., gut barrier function, mucosal immunity). Investigators may culture cells from patients carrying variants of interest and generate organoids from them; such patient-derived models should be representative of the ancestral diversity of IBD patients. Alternatively, investigators may introduce mutations of interest into cell lines or model organisms via genome editing methods. These experimental systems and models may be used to test the effects of potential therapeutics suggested by the functional impacts of the genetic variants characterized.
Visit our Institutionally Limited Submission webpage for more updates and other announcements.