Atmospheric Ligands in Biology

Primordial atmospheric gases had a significant role in shaping evolution, and determined the origin and extinction of many species. These gases are ligands across all biological systems and constitute a unique class of biomaterials. They are highly membrane-permeable, capable of readily conveying signals in an autocrine, paracrine and/or juxtacrine manner. They also exert biological activity by means of reversible and irreversible binding to prosthetic metal complexes in receptors, protein kinases, or competing against other molecules. The biological effects of these atmospheric ligands and principally oxygen (O2), nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are associated with a broad variety of biological and physiological phenomena. They share properties but do not always work independently, and can even modulate each other's activity. Despite their well-known toxicity, they are fundamental regulators of oxidative metabolism.

Oxygen is essential for healthy cellular function as the mitochondria undergo aerobic respiration. Mitochondrial diseases encompass an extraordinary assemblage of clinical problems, and play a role in the pathogenesis of a wide variety of illnesses. Although these diseases typically display a bewildering array of inherited patterns, and conventional therapies include a spectrum of genetic and molecular components, they all affect the cellular machinery which is the first to wear out, causing the transition from acute to degenerative disease. Therefore, integrative analysis of how O2 and other ligands are made available ultimately allow access to the design of therapeutic interventions and disease treatments.

The nature of the proposed research requires the translation of biological signals into quantitative measurements. These measuring techniques will result in the development of new instruments for evaluating and studying their biological function. However, a pervasive feature of these atmospheric ligands is the extremely low concentrations at which they are effective, making current detecting methods obsolete. We have a strong interest in applying our engineering knowledge and skills to this endeavor, with the aim of developing new measuring techniques for gaseous ligands, from intracellular to whole organism. In this context, we plan to develop time and frequency domain hybrid bio-optical sensors to measure O2 and NO concentration in living tissues. These biooptical sensors will have improvements in accuracy, detectability, and practicality to assess and understand their metabolism in health and disease. Additionally, we expect to design measuring strategies to study atmospheric and environmental changes based on gaseous ligands effects on biological systems.

The most exciting perspective for atmospheric gaseous ligands is their implications in regulation. Until now, cell-to-cell communication has only involved electrical and neurotransmitter conduction; however, my current findings suggest endogenous and exogenous NO, CO and H2S can induce effects throughout the entire organism. In essence, my work shows that O2, NO, CO and H2S are linked, and, if properly managed, can provide a direct control of homeostasis and treatments to diseases.