NIH/NHLBI – New Research Directions that Advance the NHLBI Strategic Vision Normal Biology (R21 – Clinical Trial Not Allowed)

November 12, 2018 by School of Medicine Webmaster

The purpose of this Funding Opportunity Announcement (FOA) is to support pilot studies by investigators with current R01-equivalent grant funding in high priority areas of research on normal biology as described by Objective 1 of the NHLBI Strategic Vision. Research on fundamental biological processes that have relevance to multiple HLBS diseases is of particular interest.  “Normal” biology includes homeostatic regulation of biological systems and the phenomenon of “resilience” – the capability of some individuals to maintain or restore normal function despite aging or environmental exposures that predispose to disease in others.

NHLBI intends to support research through this FOA that relates to the normal or “healthy” functioning of human cells and organs that are critically involved in heart, lung, blood, and sleep disorders. Of particular interest are studies that may reveal the basis of resilience. The focus of this FOA on normal human biology does not preclude studies of non-human model systems or of reversible responses to stimuli that may cause disease. However, research using cells or tissues derived from individuals with established disease is not likely to reflect the “normal” condition.

Understanding normal biology is the backbone of all biomedical science. It is essential for understanding homeostatic maintenance, predicting how biological systems respond to their environment, and recognizing disease and targets for intervention. Research on normal biological function—including emerging topics such as circadian rhythms, the microbiome, and understanding how tissues develop from progenitor cells—can help us to better define health and understand the earliest origin of disease processes. The scope of research on normal biology can range from single cell analytics to studies of entire healthy populations. Such research can reveal the molecular factors and biological mechanisms that provide the resiliency essential for sustaining wellness in the face of the aging process, stressors, and adverse influences. Gaining new knowledge about the body’s intrinsic reparative capacity could yield greater insight into the transition from health to disease. For these reasons, understanding normal biology is a cornerstone of NHLBI-funded research and the focus of this FOA.

Specific Areas of Research Interest

The research proposed through this FOA should aim to clarify biological processes that are both present in healthy humans and likely to be relevant in HLBS disorders, either because they may be altered in disease or because of their importance in countering abnormalities associated with disease.  Emphasis should be on the status and functions of these biological processes in the normal, healthy state.  This does not preclude research on the responses of molecular and cellular systems to perturbations, and in fact, interpersonal or temporal variations in responses to challenges may relate to resilience.  However, tissues derived from individuals with existing HLBS disease and model systems that have undergone irreversible changes consistent with disease are not appropriate for studies of “normal” biology.  Examples of research on “normal” system may include, but are not limited to, the following:

  • Describing the regulation of cell functions by complex gene networks and cell-to-cell interactions.
  • Studying molecular and structural mechanisms that allow cells to sense, integrate, and respond to mechanical cues and influences.
  • Characterizing innate and adaptive immune system mechanisms that promote HLBS health and prevent development of HLBS diseases.
  • Determining the influence of the microbiome (including virome and fungome) on the immune system and on HLBS health and resilience, including developmental processes, across the lifespan.
  • Investigating the potential role of mitochondrial health, genetics, and energetics as contributors to cell/tissue/organ resilience.
  • Defining the basic pathways that underlie effects of circadian function, synchronization, and harmonization on HLBS health and resilience across the lifespan.
  • Characterizing circadian regulation of the effects of environmental exposures (e.g., cigarette smoke, particulates, pathogens, temperature, humidity) on functions of the heart, lungs, and blood systems.
  • Identifying regional variations of molecular and cellular function in the lung, heart, and vascular beds.
  • Characterizing the diversity and plasticity of heart, lung, and blood cells using unbiased approaches such as single cell omics analyses.
  • Gaining fundamental knowledge of the glycome and its regulation, and the role of post-translational modification of proteins in regulating function of HLBS systems.
  • Elucidating structural and matrix biology as needed to better understand injury, regeneration, and repair of the normal (or developing) heart, lung, and blood tissues and to enable regenerative medicine.
  • Characterizing mechanisms that underlie sex/gender differences in heart, lung, and blood systems and their differential susceptibility to disease.

This FOA is not intended to support the following types of projects:

  • Applications that propose to identify or study the pathogenetic basis of particular diseases.
  • Applications that propose to identify therapeutic targets or develop approaches to disease treatment.
  • Studies of biological systems or mechanisms that will not contribute to understanding heart, lung, blood, or sleep function in humans.

Deadlines:  standard dates apply


Filed Under: Funding Opportunities