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Publication Date - 12/3/1999

13. NIH/NHLBI - Oxygen Sensing during Intermittent Hypoxia

The National Heart, Lung, and Blood Institute announces a request for applications (RFA) that focus on Oxygen Sensing during Intermittent Hypoxia. This RFA is designed to stimulate molecular, genomic, and biophysical approaches to studying the effects of intermittent hypoxia on gene expression, cellular signaling pathways, and oxygen sensing in a variety of tissues.

Applicants must propose hypothesis-driven studies that address the molecular effects of brief intermittent systemic or local hypoxia (repetitive hypoxic episodes lasting up to two minutes) as it occurs in diseases like sleep apnea and sickle cell microvascular occlusions. Research should be linked to understanding the role of intermittent hypoxia in disorders affecting the heart, vasculature, lung, blood, or sleep. Some illustrative examples are listed below:

• the signal transduction, gene regulating, and mitochondrial mechanisms that mediate oxygen sensing during intermittent hypoxia in central and peripheral tissues, and of the time course and oxygen level thereshold for adaptive changes in cellular, local, or systemic responses;
• the role of intermittent hypoxia in tissue injury produced by alterations in mitochondrial electron transport, mitochondrial genome damage, or oxidant and excitotoxic stress contributing to heart, lung, blood, or sleep disorders;
• development and use of noninvasive approaches and biomarkers for tissue-specific mapping of changes in gene expression and the cellular injury produced by intermittent hypoxia, and to identify and assess oxidative injury and vascular inflammation in brain and other tissues at early time points in sleep apnea patients;
• development and use of animal models to elucidate the cellular mechanisms mediating effects of intermittent hypoxia on autonomic control of heart rate, cerebral blood flow, respiration, or the daily rhythm of cytokine-immune and endocrine function;
• the role of intermittent hypoxia and abnormal oxygen sensing in polycythemia vera;
• molecular effects of intermittent hypoxia on hematopoiesis, including megakaryocyte development and platelet production.

The support mechanism for this RFA will be the NIH research project grant (RO1). The NHLBI intends to commit $3.6 million in FY 2000 to fund up to 14 - 16 new grants with a project period of up to four years and a budget for direct costs of up to $175,000 per year. The anticipated award date is September 30, 2000.

A Letter of Intent to Apply is requested to arrive at the NHLBI on or before JANUARY 24, 2000. Applications are due at the NIH Center for Scientific Review on or before FEBRUARY 23, 2000.