Rotation Projects

Work in our lab uses optical imaging to study live cells and organisms. This multi-disciplinary approach brings together the areas of synthetic organic chemistry, molecular biology, biochemistry and cell biology, with translation into mouse models of disease.

1) Broadening the scope of bioluminescence: Bioluminescence results from the chemical generation of light that occurs when a luciferase enzyme oxidizes its small molecule luciferin substrate. We have synthesized a wide variety of novel luciferin substrates designed to improve the ability to detect bioluminescence signals. In parallel, we have mutated luciferases to best accommodate these substrates, and have also found that a homologous protein in the fruit fly can act as a luciferase. Projects in the lab range from basic molecular-level biochemical, chemical, and evolutionary studies of luciferases and luciferins, to powerful applications such as imaging of enzyme activity and drug action in the brains of live mice.

2) Fluorescent probes beyond the visible range: Fluorescent sensors of enzymatic activity, metal ions, and small molecules allow the optical detection of biologically-important molecules. However, most of these sensors are based on visible-wavelength fluorophores that suffer from photoxicity and high background. These probes thus have limited utility in live cells, and are generally unusable in live organisms such as mice. We are designing and constructing sensors that fluoresce in the near-IR, beyond the visible range, which is most suitable for non-invasive optical imaging of the physiological state of live cells and organisms.