The fluorescent proteins revolutionized our ability to study protein function directly in the cell by enabling individual proteins to be selectively labeled through genetic encoding of a fluorescent tag. As researchers seek to make increasingly sophisticated dynamic measurements of protein function in the cell to unravel molecular mechanism, we designed a chemical tag to combine the advantages of genetic encoding with a modular organic fluorophore. With TMP-tag, the protein of interest is tagged with E. coli dihydrofolate reductase, which can subsequently be labeled with a cell permeable trimethoprim-fluorophore conjugate. Here we demonstrate that TMP-tag is a robust cellular reagent. We present recent results exploiting the modular nature of the chemical tag to generate TMP-tags for specific applications in single-molecule, super-resolution, and multi-color imaging. We look forward to innovations at the interface of chemical tag technology and spectroscopy for biological imaging.
Virginia W. Cornish graduated summa cum laude from Columbia University with a B.A. in Biochemistry in 1991, where she did undergraduate research with Professor Ronald Breslow. She earned her Ph.D. in Chemistry with Professor Peter Schultz at the University of California at Berkeley and then was a Postdoctoral Fellow in the Biology Department at M.I.T. under the guidance of Professor Robert Sauer. Virginia joined the faculty of the Chemistry Department at Columbia in 1999, where she carries out research at the interface of chemistry and biology, and was promoted to Associate Professor with tenure in 2004 and then Professor in 2007. Her laboratory brings together modern methods in synthetic chemistry and DNA technology to expand the synthetic capabilities of living cells. Her research has resulted in 59 research publications and several patents and currently is supported by multiple grants from the NIH and NSF. Virginia has been recognized for her research by awards including an NSF Career Award (2000), a Sloan Foundation Fellowship (2003), the Protein Society Irving Sigal Young Investigator Award (2009), and the American Chemical Society Pfizer Award in Enzyme Chemistry (2009). In addition to her research and teaching, Virginia enjoys spending time with her husband and their three children.