Welcome to the Xie Group homepage. We are a group of scientists working at the interface of several disciplines, striving to develop new physical and chemical tools to solve compelling biological problems.

Advances in biology over the past half-century can best be summarized as understanding biology at the molecular level. We have now sequenced the genomes of many species, including humans, and obtained high-resolution structures of many macromolecular machineries. What are the new challenges of the post-genomic era? Well, there are many. One challenge, in particular, is to study how molecular machineries actually work - how they work in real time, how they work individually, how they work together, and finally, how they work inside live cells.

Physical tools have always facilitated advances in biology. Notable examples are crystallography and DNA sequencing. In recent years, due to contributions from numerous research groups, single-molecule experiments have changed the way many biological problems are addressed. Knowledge from these experiments continues to emerge. Our group was one of the first to pioneer fluorescence studies of single molecules at room temperature in the early 1990s and has since made important advances in single-molecule enzymology and protein conformational dynamics. Our work has been credited not only for bringing about technological innovations, but for generating new insights on important scientific issues as well.

There are many reasons to use the single-molecule approach in biology. The most important is that single-molecule experiments generate movies of motions and biochemical reactions of macromolecular machineries, which are particularly helpful in elucidating their mechanisms. In tandem, we are also studying DNA protein interactions on several nucleic acid enzymatic systems, including DNA polymerase and DNA repair enzymes.

Recently we have applied single-molecule experimentation to live cells and have begun real-time imaging of gene expression, at both transcription and translation levels. To accomplish this, we have developed several strategies to achieve single-molecule sensitivity with high specificity, millisecond time resolution, and nanometer precision in a living cell. We have observed protein being generated one molecule at a time in E. coli cells, and studied how a transcription factor binds to DNA and regulates gene expression. We found that a single-molecule event can be solely responsible for the life changing decision of a cell.

Finally, we continue to push for new imaging technologies. Our group has lead in the rapid development of Coherent Anti-Stoke Raman Scattering (CARS) microscopy since 1999, and was recently superseded by Stimulated Raman Scattering microscopy (SRS). These are label-free imaging techniques based on vibrational spectroscopy, and are capable of real-time, noninvasive examination of living cells and organisms. Orders of magnitude more sensitive than conventional Raman microscopy, they allow mapping of 3D distributions of small molecules, such as metabolites and drugs, as well as tumor identification in tissues, which open many exciting new possibilities for biology and medicine.

We are in a new era, when biology is becoming a data-rich, quantitative science with a wealth of physical and chemical tools. Our group is happy to make both scientific and technological contributions to biomedicine at this exciting time.

Sunney Xie