Notice of Special Interest (NOSI): Promoting Fundamental Research on Mitochondrial Involvement in Lung Diseases and Sleep Disorders
Notice Number:

Key Dates

Release Date:

December 22, 2021

First Available Due Date:
February 05, 2022
Expiration Date:
April 05, 2025

Related Announcements

PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Issued by

National Heart, Lung, and Blood Institute (NHLBI)



The purpose of this NOSI is to stimulate research focused on cell-type-specific signatures of mitochondrial behavior in healthy and diseased lungs. Multidisciplinary collaboration among experts in recently developed technologies, such as iPS cell and lung progenitor/organoid culture systems, advanced single cell-and “-omic” technologies, and lung cell biology is encouraged. We encourage investigators to Utilization oflung cells from human donors and animal models with respiratory diseases and/or well-defined congenital mitochondrial diseases is also encouraged.


Mitochondria are abundant, complex and dynamic cellular organelles well known for their vital role in energy production. Remarkably, in addition to ATP production, recent studies have revealed critical functions of mitochondria in a wide range of other biological processes, such as biosynthesis, ion homeostasis, innate immunity/inflammation, epigenetic modification, signaling, cell survival and proliferation, and stem cell/adult progenitor cell maintenance and fate. These novel functions position mitochondria as central players in aging and in the pathogenesis of an expanding list of diseases, including lung diseases and sleep disorders. Nevertheless, little is yet known about the contributions of mitochondrial dysfunction to lung and sleep disorders.

Challenges to this research have included the diversity and complexity of lung cell types and structures, the multiple causes and risk factors for most respiratory disorders, and the multiplicity of mitochondrial functions. In addition, research to characterize cell type-specific mitochondrial functions in healthy and diseased lungs across the life span will require multidisciplinary collaborations and utilization of advanced technologies, such as lung stem cell biology, single cell analytics and omic technologies for mitochondrial derived metabolites. Fortunately, recent methodological advances and the availability of a large number of animal models of mitochondrial diseases offer unprecedented opportunities for progress in this area.

Objectives and Selected Research Examples:

This NOSI is intended to encourage partnerships between pulmonary researchers and experts in mitochondrial biology to carry out collaborative studies of mitochondrial biology in particular lung cell types. This research is expected to reveal novel mechanisms and new therapeutic targets for chronic lung diseases and sleep disorders.

This NOSI encourages, but is not limited to, research applications exemplified by the following objectives:

• Investigate how congenital mitochondrial mutations affect lung cellular function with or without additional stressors that are key in the development and progression of lung and sleep disorders.

• Map mtDNA and nDNA mutations affecting mitochondria in aged or diseased human lung cells and investigate how these mutations influence cellular function and aging or disease phenotypes.

• Study whether and how mitochondrial dysfunction affects lung progenitor cell fate, maintenance and regeneration capacity after acute lung injury.

• Investigate how mitochondrial dysfunction may lead to abnormal host responses to SARS-CoV-2 infection using animal model or human lung cells culture systems, such as lung organoids.

• Study the impact of mitochondrial stress on the epigenetic modification and cellular function of lung cells in respiratory disorders such as Bronchopulmonary Dysplasia (BPD).

• Define cell-type-specific mitochondrial-derived metabolites and peptides, and demonstrate their downstream targets and roles in the pathogenesis of lung and sleep disorders.

• Mine mtDNA, nDNA, and RNAseq databases to discover dysregulated interactions between mitochondrial and nuclear genomes in lung pathogenesis.

• Investigate the effects of mitochondrial therapeutics, including mitochondrial-active drugs and mitochondrial transfer technologies, in models of lung diseases.


Application and Submission Information

This notice applies to due dates on or after February 5, 2022 and subsequent receipt dates through April 5, 2025.

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

  • PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

NHLBI will accept only mechanistic studies that meet the NIH definition of a clinical trial (see NOT-HL-19-690) in response to PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required) and its reissues. For additional information, please see the NHLBI Policy Regarding Submission of Clinical Trial Applications Notice (NOT-HL-18-611) to identify the most appropriate FOA.

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

  • For funding consideration, applicants must include “NOT-HL-22-003” (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.


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

Scientific/Research Contact(s)

Jining Lu
National Heart, Lung, and Blood Institute (NHLBI)
Division of Lung Diseases
Telephone: 301-827-2807

Qing Lu
National Heart, Lung, and Blood Institute (NHLBI)
Division of Lung Diseases
Telephone: 301-480-9158

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Anthony Agresti
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8014