Chloride is an essential inorganic ion for life. Beyond its role as an electrolyte, chloride mobilization across cellular membranes is known to be involved in a wide range of homeostatic processes including, but not limited to, pH regulation, fluid excretion, and electrical activity. The growing importance of chloride in normal physiology and disease is further evident by recent discoveries of new transporters and biological roles, which have been accelerated through the application of fluorescent sensors for chloride. The fluorescence imaging of chloride in living cells is linked to our ability to build hosts that can recognize chloride in water, a fundamental challenge in the field of supramolecular chemistry. New advances along these lines remain rare due to the inherent thermodynamic barrier for desolvation of the chloride ion. To address this challenge, we use and evolve Nature to build protein-based hosts for chloride. Even though there are only twenty proteinogenic amino acids, protein sequence space is vast and can be further enriched through protein engineering methods. By selecting for a desired function or property, laboratory-guided evolution allows for this sequence space to be quickly sampled and filtered. For our goal, this approach affords a diverse pool of hosts that can further evolved, characterized, and applied. To this end, I will describe how rhodopsins and green fluorescent proteins can serve as platforms to build fluorescent sensors for chloride and, more broadly, serve as biological supramolecular hosts to advance our fundamental understanding of anion recognition in aqueous systems.
Sheel was born and raised in Plano, Texas. She earned her B.S. degree in Chemistry from The University of Texas at Dallas in 2007 where she carried out research in the laboratory of Professor John Sibert synthesizing redox-active macrocycles for metal sensing. Then Sheel pursued her graduate studies at the University of California, Berkeley under the supervision of Professor Christopher Chang. Her graduate work focused on the synthesis and application of new small molecule fluorescent probes and related analytical imaging technologies to uncover new roles for transition metals in cellular signaling. After completing her Ph.D. in 2013, she joined the laboratory of Professor Frances Arnold at the California Institute of Technology as an NIH postdoctoral fellow. There she employed a multipronged approach, encompassing protein crystallography, enzymology, and directed evolution to understand the structure-function relationship of nitrating cytochrome P450s, resulting in the discovery of new enzymes and natural products. In August 2016, Sheel came back to The University of Texas at Dallas and joined the faculty in the Department of Chemistry and Biochemistry. Since starting, Sheel and her team have received grant support from the University of Texas System STARs program, Welch Foundation, and National Institute of General Medical Sciences. Recently, Sheel was awarded the 2020 Sessler Early Career Researcher Prize.