Qiliang Liu comes to Emory from the University of Science and Technology of China. He was attracted to Emory for its research excellence, particularly the work of Craig Hill and Tim Lian. In the first year, he is also excited about serving as a TA and getting involved in all aspects of the PhD experience. His research interests include light-driven hydrogen production, solar energy, and photocatalytic devices.
Kevin Fish comes to Emory from the University of California, San Diego. At Emory, he is excited about pushing the limits of his knowledge and progressing in research. Outside of chemistry, his interests include playing the guitar and the piano and working out. On his drive to Atlanta, he lived in a tent for a week while passing through Utah.
Divisions of Interest: Biomolecular, Organic, Physical
Namkhang Tsamchoe comes to Emory from Sarah Lawrence College. Before coming to the United States, Namkhang studied in India and in England. Namkhang chose Emory for the amazing chemistry faculty, the outstanding research facilities, and the new Atwood chemistry building. Her research interests include synthetic inorganic chemistry, organic chemistry, catalysis, drug discovery, and organometallics and she is particularly excited to further develop her synthetic skills at Emory. One of her research goals is to find a more sustainable way of fixing atmospheric nitrogen. When she isn’t in the lab, Namkhang applies her love of chemistry to cooking.
Divisions of Interest: Inorganic, Organic, Physical
Enzymes are responsible for catalyzing a myriad of reactions necessary for life. Because enzymes play such an important role in human physiology, they are often targets for drugs and disease treatments. Naturally occurring enzymes are capable of catalyzing a wide variety of reactions, but imagine if we could design an enzyme to catalyze any reaction we wanted. We would be able to create new antibiotics easily to combat antibiotic resistance or to quickly synthesize chemicals for industrial applications. Scientists have made a lot of progress towards creating new enzymes, yet there are still roadblocks. Modifying existing enzymes through directed evolution is inefficient and limited by the need for high throughput screening methods. Conversely, in the case of rational design, we are missing key information for the technique to work at its full potential.
My research works to fill in the gaps in our knowledge to allow for the efficient development of new enzymes. A large portion of the scientific community focuses on determining the structure of enzymes and how the structure impacts function. While this work is enormously important, it doesn’t tell the full story. One major aspect that is often overlooked when examining structure-function relationships is that enzymes are dynamic molecules. This means that they physically move, bend, wiggle, and change shape during catalysis.
To study enzyme dynamics, I use temperature jump spectroscopy. There are only a few labs around the world that use this technique, and even fewer that use it to study enzymes. Temperature jump spectroscopy relies on rapidly initiating a change in equilibrium. For example, my samples contain enzymes and ligands. As determined by the equilibrium constant, some of the ligand is bound and some ligand is free in solution. The sample starts at equilibrium at a specified temperature. Then, a laser pulse is used to rapidly heat a small portion of the sample. The system must relax to a new equilibrium at the higher temperature. Since ligand binding is an exothermic reaction, there will be a net flux of ligands dissociating from the enzyme. However, as a system relaxes to a new equilibrium it will shift in the forward and reverse directions providing information about both processes. From this data I can determine the rate at which ligands are binding and unbinding, accompanying enzyme motions, and even conformational changes unrelated to ligand association. These changes occur on the microsecond timescale.
Although temperature jump spectroscopy could be applied to any number of enzymes, so far I’ve studied one enzyme in particular, dihydrofolate reductase (DHFR). It is a small ubiquitous enzyme that is well known for changing conformations during its catalytic cycle. Thus, it is a good starting place for understanding enzyme dynamics. Furthermore, DHFR is an important enzyme for nucleic acid synthesis. Since nucleic acid synthesis is necessary for cellular replication, DHFR inhibition is a strategy for anticancer and antibacterial agents.
Understanding the motions of DHFR could lead to the development of new inhibitors to combat resistance developed in certain cancers. The technique I use can be applied to other enzyme systems as well. By studying multiple enzymes we can build an understanding of enzyme motions in general, which can then be used to inform computational simulations for rational enzyme design. This would ultimately allow us to efficiently design new enzymes as well as new drugs.