Objective 1: Understand normal biological function and resilience

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. Using gold standard and emerging tools, methodologies, and technologies, such research can uncover the biological factors, behaviors, lifestyle factors, social circumstances, and environmental exposures that enable 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 will yield greater insight into the transition from health to disease. For these reasons, understanding normal biology must remain a cornerstone of NHLBI-funded research.

Envision a future in which we are able to...
  • Promote resilience and healthy aging through the application of normal and reparative biology using cells (e.g., progenitor cells) that enable the regeneration and repair of heart, lung, blood, and sleep (HLBS) systems.
  • Use emerging nanoscale imaging technologies (e.g.,cryo-electronmicroscopy) and single-cell analytics to characterize the molecular signature of the homeostatic state of HLBS systems that sustain health and wellness.
  • Generate a better understanding of how environmental exposures, social determinants, and behaviors (e.g., diet and physical activity) modulate biological systems such as the epigenome, microbiome, and immune system to sustain health and promote resilience.

Related Priorities

Compelling Question
How are normal cell functions regulated by complex gene networks and cell-to-cell interactions? (1.CQ.01)
Compelling Question
What are the key molecular and structural mechanisms that allow single cells and tissues to sense, integrate, and respond to mechanical cues and influences at local and systemic levels? (1.CQ.02)
Compelling Question
What are the molecular, developmental, hormonal, and behavioral mechanisms and psychological, social, and environmental factors-evaluated with a systems biology approach-involved in maintaining healthy weight across the lifespan? (1.CQ.03)
Compelling Question
What are the mechanisms and range of normal physiologic responses to environmental, neuropsychiatric, social, and other stimuli that predict homeostatic resilience or transition to disease across the lifespan? (1.CQ.04)
Compelling Question
What innate and adaptive immune system mechanisms promote HLBS health and prevent development of HLBS diseases? (1.CQ.05)

Overarching Objectives

  1. Understand normal biological function and resilience
  2. Investigate newly discovered pathobiological mechanisms important to the onset and progression of HLBS diseases
  3. Investigate factors that account for differences in health among populations
  4. Identify factors that account for individual differences in pathobiology and in responses to treatments
  5. Develop and optimize novel diagnostic and therapeutic strategies to prevent, treat, and cure HLBS diseases
  6. Optimize clinical and implementation research to improve health and reduce disease
  7. Leverage emerging opportunities in data science to open new frontiers in HLBS research
  8. Further develop, diversify, and sustain a scientific workforce capable of accomplishing the NHLBI’s mission