Structure and function of enzymes
Virtually every living process, whether it is programmed cell death, mitosis, HIV infection, or embryonic development involves proteins. Indeed, the term protein is derived from the Greek word proteois, which means “first.” My laboratory has had a long-standing interest in protein structure and function where we utilize a combination of biophysical and biochemical techniques to address important mechanistic questions.
We are presently studying a variety of fascinating enzymes that are involved in the biosynthesis of di-, tri-, and tetradeoxysugars. These unusual carbohydrates control or alter the behavior of a wide range of biological molecules. They are found, for example, on the O-antigens of Gram-negative bacteria, and indeed there is growing evidence that O-antigens play important physiological roles including, but not limited to, virulence, effective colonization of host tissues, protection from phagocytosis and serum-mediated killing, and resistance to antimicrobial peptides. As such, the enzymes involved in the productions of these unusual sugars may serve as important drug targets.
In addition to being found on O-antigens, many of these unusual sugars have been observed on various antibiotics, antifungal agents, and chemotherapeutics. Importantly, it has been demonstrated that these carbohydrates provide or enhance the pharmacological properties of the macromolecules to which they are attached. By understanding the structures and functions of the enzymes involved in the biosynthesis of unusual sugars, it should be possible to enzymatically produce novel “designer” carbohydrates with new biological properties that extend far beyond their current function. Indeed, we have already produced three unusual sugars that are not normally encountered in Nature. Clearly we are limited only by our imagination once we understand how these complex biomolecules are synthesized and how new compounds can be generated.
My laboratory is not limited to basic research, however. We believe that science should be taken out of the Ivory Tower and made accessible to the general public. As such, we established an outreach program known as Project CRYSTAL in 2009 (http://www.projectcrystal.org and https://www.facebook.com/ProjectXTAL). The main objective for Project CRYSTAL is to provide hands-on laboratory experience to middle school students to encourage a future career in science. So far the project has been featured on the cover of the journal Biochemistry, has been written up as an NSF Exemplary Project, has been featured in C&E News, has been reported on by the National Science Teachers Association, has been highlighted on the University of Wisconsin News webpage, has been described in the Protein Data Bank Newsletter, and has been highlighted in Wisconsin’s Magazine for the Life Sciences. Excitingly, six of the middle school students that have participated in the program have served as authors on papers published in Biochemistry. Our long-term goal is to expand this program to other universities in the United States in order to improve middle school science education throughout the country. To this end, a new Project CRYSTAL is presently being established at Indiana University-Purdue University Indianapolis.
Research in the laboratory is funded by both the NIH and the NSF.