Student Spotlight: Ryan Fan Reflects on his “Summer in Siena”

From L to R, Alexis Kosiak, Ryan Fan, and Alex Nazzari visting the lab of Gianluca Giorgi, a collaborator of Emory chemist Vince Conticello, at the University of Siena.
From L to R, Alexis Kosiak, Ryan Fan, and Alex Nazzari visting the lab of Gianluca Giorgi, a collaborator of Emory chemist Vince Conticello, at the University of Siena.

“Sprawling in Siena”

By: Ryan Fan (Emory College)

Without a data plan or service to access a map, and with street signs posted on obscure buildings rather than poles, roaming around Rome turned a “15 minute walk” to our hotel into an hour of circling the same street over and over again. “Well, this is going to be difficult,” I thought as I entered my hotel room, passing out from jet lag. I sincerely hoped I wouldn’t continue to feel as lost and disoriented as I did on that first day.

Thankfully, most of the study abroad experience in Italy went better than my first hour in Rome. “Getting lost” turned into culturally-motivated wandering—from the Coliseum to the Vatican Museum to the 551 steps of St. Peter’s Basilica. My personal favorite experience was climbing the Basilica to see the view of Rome’s skyline. But it wasn’t solely a race to the top – climbing the dome was special for what you see on the way. At about 200 steps, you get a birds-eye view into the Basilica. Pilgrims travel thousands of miles to see the work of artists like Michelangelo and the crypts of Paul and Peter. The whole climb, from start to finish, was a privilege.

Studying chemistry in Italy gave me a behind-the-scenes view of some of what goes into restoring and protecting the kind of art that I admired in the Basilica . One thing we studied in particular was the use of lasers to restore art and architecture. I have always thought of art as purely a humanities discipline. However, we learned that while artists are the ones to make beauty, scientists are needed to help preserve it. Every time a piece of art needs to be restored, it requires an entire team of art and science experts. Part of their goal is to make the smallest amount of alterations possible while restoring a piece. As a chemistry and creative writing double major, this changed my perception that my two fields of study are mutually exclusive. Rather, they can co-exist together to form the best possible product. This also happens in developing makeup, making art supplies, and authenticating pieces of art.

We arrived in Siena, a city in Tuscany on May 27, 2016. One of my favorite things about Siena was the massive hills. As a cross country runner, I found no shortage of places to run because of the hills, which increase the difficulty of my training. The central square, El Piazza Del Campo, is the heart of the city with tourists and native residents alike picnicking at every hour of the day. El Piazza houses a biannual historical race known as the Palio di Siena. This is a horse race with 10 jockeys, each representing a contrada, or district, of the city. A victory brings tremendous pride and celebration to a contrada. After six weeks of living in Siena, we ended our program by attending this raucous event alongside nearly 50,000 other spectators. Of course, as an Emory student-athlete, I support the Eagle contrada.

The only complaint I have about the Summer in Siena program is that it goes by too fast. It feels like just a second ago that I was feeling lost and nervous in Rome. I initially went on this trip just to study chemistry, but I’ve learned so much more about art, culture, and collaboration between the arts and sciences on the way. When I get home, I plan to try to convince my mom that we should take a trip to Italy as a family–that’s the only way I can truly show them how great this experience was.

Interested in applying to for the “Summer in Siena” program? Details are available on the Center for International Programs Abroad (CIPA) website.

Research Spotlight: A Unique Method for Studying Enzymes

Morgan in the lab. Photo provided by Morgan Bair Vaughn.
Morgan in the lab. Photo provided by Morgan Bair Vaughn.

By: Morgan Bair Vaughn (Dyer Group)

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.

Further Reading

Reddish, M. J.; Vaughn, M. B.; Fu, R.; Dyer, R. B. Ligand-Dependent Conformational Dynamics of Dihydrofolate Reductase. Biochemistry 2016, 55 (10), 1485-1493.

 

Bowman Group Published in Science

The Bowman Group has had two publications in Science so far this year. The first one, “Quantum Deconstruction of the Infrared Spectrum of CH5+” appeared in the Jan. 6, 2006 issue, and the second one, “Signature of H2CO Photodissociation from Two Electronic States” appeared in the March 10, 2006 issue.

Dr. Bowman was also recently elected a fellow of the American Association for the Advancement of Science.