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

The advances in biology over the last 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. For instance, we would like to know 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, DNA sequencing, and microarray techniques. 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. Along this line, we are also studying DNA protein interactions on several nucleic acid enzymatic systems, including DNA polymerase and DNA repair enzymes.

Recently we have taken the single-molecule experiment to live cells and have begun real-time imaging of gene expression, both at the transcriptional and translational level. 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 state-of-the-art techniques for imaging intracellular dynamics. Our group has led in the rapid development of coherent anti-Stokes Raman scattering (CARS) microscopy, which allows imaging of live cells and organisms based on vibrational spectroscopy. This allows noninvasive imaging of small molecules, such as metabolites and drugs, without the introduction of natural or artificial fluorophores. Meanwhile, CARS is becoming a powerful imaging method for biomedicine. For example, it enables imaging of skin at the video rate, mapping the distribution of lipids, water and drug molecules, as well as brain tissue with the ability to identify brain tumors.

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

Sunney Xie