Inorganic ions are essential nutrients for all forms of life, found over a wide concentration range with varying physical properties such as size, shape, and charge. To maintain global ion homeostasis at the organismal, tissue, cellular, and subcellular levels, biological receptors have evolved to selectively recognize and position ions with spatial and temporal fidelity, thus requiring a high degree of thermodynamic and kinetic control. Along these lines, cations are well-studied and elegant cell biology and biochemical studies continue to advance our understanding, but comparatively their anionic counterparts are not. Freely diffusing and protein-bound anions together with anionic protein modifications link to nutrient acquisition, electrical activity, and even hormone metabolism; however, a breakdown in cellular homeostasis can lead to anion dysregulation in a wide range of diseases including cancer, cystic fibrosis, and neurological disorders.
Given this biological significance, molecular technologies can accelerate and enable the identification of the cellular pools, targets, and roles of biologically relevant anions but are underdeveloped. Advances to this end are linked to our ability recognize and manipulate anions in water, a fundamental challenge in the field of supramolecular chemistry. To fill this gap, we study interactions between anions and protein-based hosts to engineer new technologies for applications in living cells. Our results will define the molecular criteria required for aqueous anion recognition and contribute to the fundamental understanding of the roles for anions in cellular signaling with implications in the diagnosis and treatment of associated diseases. Current projects include 1) characterizing prokaryotic oxyanion binding proteins with biophysical and in silico methods, 2) discovering and engineering fluorescent protein-based biosensors for halides and oxyanions with natural, laboratory, and in silico-guided evolution strategies, and 3) probing the roles of halides in bacterial and mammalian cells with microscopy, pharmacology, and genetics.
We are grateful for research support from the University of Texas at Dallas, University of Texas System Rising STARs program, Welch Foundation, and National Institute of General Medical Sciences of the National Institutes of Health.