Key Dates

Related Announcements

• May 07, 2020 – NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195
• May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

This Notice of Special Interest (NOSI) encourages applications that focus on the development and validation of tissue-, stem-, or progenitor-cell-derived “3D” organotypic culture models (OCM) for transplantation immunology research.

Background

OCM offer several advantages over traditional 2D cell cultures including improved modeling of tissue architecture, cell-cell interactions, and other microenvironmental aspects of tissues and organ systems. To that end, kidney, lung, liver, intestinal, pancreatic islet, spleen, and lymph node organoids are being developed for or are currently used in experimental regenerative medicine applications as well as cancer, autoimmune, and infectious disease research.

Recent developments in OCM are extending the potential utility of these models to investigate complex immunological systems in vitro. Microphysiological systems (MPS) with multiple microfluidic chambers can be used to control differentiation of organoids under mitogen gradients, promote organoid vascularization, and model organ-organ interactions. Technological advancements in biofabrication and 3D printing can generate complex scaffold structures representative of organs with improved reproducibility and scalability. The development of non-immunogenic synthetic or de-cellularized matrices to support organoid formation is another active area of research. This NOSI aims to leverage recent advances in OCM to promote the development of these tools for transplantation immunology research.

Research Objectives

This NOSI will support applications that focus on development of allogeneic or xenogeneic OCM to study immunologic features of transplant-related diseases or conditions, including:

• Cellular rejection, antibody-mediated rejection, or mixed cellular and antibody-mediated rejection
• Sensitization, i.e., immunogenicity of pre-existing allo-reactive or xeno-reactive antibodies
• Tolerance and/or accommodation, i.e., resistance of an organ to immune-mediated damage
• Zoonotic infection in the context of immunosuppression and exposure to a xenograft
• Graft-versus-host disease
• Transplant related ischemia reperfusion injury

Applications supported under this NOSI will include validation studies that compare data obtained from the OCM to clinical and/or experimental in vivo data (new or preexisting) and establish analogous OCM endpoints (i.e., for graft injury, dysfunction, rejection, tolerance, etc.). Use of cutting-edge technologies and interdisciplinary collaborations that apply progress made in other fields to OCM for transplantation immunology is encouraged.

Applications proposing any of the following will NOT be supported under this NOSI:

• “2-D” in vitro culture systems
• Transplant organoids in vivo as a replacement or regenerative therapy

Application and Submission Information

This notice applies to due dates on or after February 5, 2024 and subsequent receipt dates through November 16, 2026.

Submit applications for this initiative using one of the following notice of funding opportunity announcements (NOFOs) or any reissues of these announcements through the expiration date of this notice.

• PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PA-20-185  - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the notice of funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-AI-23-064” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Shilpa Kulkarni, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-747-7365
Email: shilpa.kulkarni@nih.gov