On Wednesday, July 18th, Morgan Vaughn successfully defended her thesis, “Enzyme Dynamics Elucidated via Temperature Jump Fluorescence Spectroscopy”. Morgan’s thesis committee included her thesis advisor, Dr. Brian Dyer, and members Dr. Stefan Lutz and Dr. Vincent Conticello.
This Fall, we are publishing a special series of blog posts about applying to graduate school–at Emory and in general. Our goal is to demystify the application process and help applicants feel confident as they seek a home for their graduate studies. This post is the fourth in the series, an interview with current graduate student, Morgan Bair Vaughn (Dyer Group).
Q. What made you decide to apply to Emory?
There were a few factors . The first is that the chemistry program is one of the top ranking programs in the country. Additionally, Emory offered opportunities that would help me gain the experience I need for my desired career after graduate school. For example, the Dean’s Teaching Fellowship is an award that provides support for students to teach their own class for a semester in their last year at graduate school. Currently, I’m teaching a section of Chem 150, which will give me valuable teaching experience beyond a teaching assistantship. Finally, Emory is in the Southeast near my family. I am close to my family so staying close to them geographically was important to me.
Q. How did you choose Emory over other schools?
Weighing the pros and cons of each school can be difficult, but the one thing that pushed me to accept Emory over other schools is that there were multiple professors at Emory that I was interested in working with. I narrowed down my labs of interest after visitation weekends, and Emory was the only place where I could see myself in more than 1 or 2 groups. The piece of advice that I heard over and over again from professors and graduate students alike was not to go to a school where there was only one professor I’d want to work for. There is no guarantee that you will get a position in the lab, even if the professor likes you. Things happen; professors move, lose funding, or can only accept so many students into their lab in a given year. Additionally, at Emory first year students do a series of research rotations to learn what it is like to work in a few different labs. Student tend to start rotations with a particular lab as their top pick, but often their top choice changes throughout the rotations as students realize that they prefer certain areas of research, or they like the environment and culture of a particular lab, or they like the mentoring style best of one professor. It is important to go to a school where you have options and a chance to explore them prior to making a final decision on which lab you join.
Q. What was the most challenging part of the application process?
I found the writing the Statement of Purpose to be the most difficult part of the application process. (Hey! We can help with that.) When I was applying to graduate school, I wasn’t sure what research area I was interested in pursuing. I had bioorganic and organic synthesis research experience from undergrad, but I also enjoyed all of my chemistry classes. All areas of chemistry seemed interesting to me! So, deciding which professors I was interested in working with was quite a challenge for me. Ultimately, I picked professors from all different divisions. This isn’t necessarily a strategy that I would recommend, but it worked out because I was able to explain why I was interested in each research group. That is the important part, explaining why you are interested in a group and how your previous experience will be helpful.
Q. Now that you’re in grad school, what have you done to be successful? What do you think successful grad students have in common?
I think the most successful graduate students are the ones who start graduate school with a goal in mind and know why they are pursuing a PhD. The reasons for going to graduate school can vary, from wanting to become a professor, patent lawyer, industrial research and design scientist, or simply to gain a very high level of knowledge in a topic of interest. Having a goal provides focused motivation and allows students to take advantage of opportunities as they arise. Starting graduate school, I knew that I enjoyed teaching and envisioned working at a primarily undergraduate institution (PUI). Since being in graduate school, I’ve learned that there are many other options for education besides the traditional classroom. Now I am considering a much wider range of career options from medical science liaison, to science communication and writing, in addition to teaching at a PUI or community college. To learn more about these opportunities I attend events on campus with Emory Alumni such as a breakfast with science writers and a Q&A session with high school teachers.
Knowing your goal is important, but so is actually completing the work required to earn a PhD. To that end, I urge students to treat getting a PhD as a marathon and not a sprint. The research necessary to write a dissertation cannot be done all at once; it takes time. The way I’ve approached it is to find a nice comfortable pace to work at, one that I’m making good progress in the lab, yet I can sustain for many years. When a big deadline or yearly report comes along I can push a little harder when necessary for a short while. Then, I go back to the same pace as before. Often, I see students in crisis mode around yearly reports, frantically trying to complete as much work as possible, only upon passing, they drop down to doing almost nothing. I don’t like to do that; it is a very stressful way to operate! Work on your project every day, bit by bit. Just like science as a whole, occasionally there are leaps and bounds, but most of science happens incrementally, bit by bit.
Q. Is there anything you wish you had known before applying to graduate school?
I wish I had known how helpful visitation weekend would be to make a final decision about which school to accept. [Note: Emory Visitation Weekend is by invitation only and will take place February 23rd-25th, 2018.] When deciding which schools to apply to, be open minded. It is difficult to know the culture and environment of a school just by looking at the website. Pick several schools where there is some research you are interested in and where you wouldn’t mind living for several years. After visiting, I had a much better idea of what each school was like. If you can’t attend visitation weekend, I highly recommend contacting the school to ask about speaking with a few of the graduate students to get their perspective. I also wish I had known that lab websites are often out of date. While the overall research area of a group doesn’t change too much over the years, the current individual projects may be quite different than what’s posted online.
Q. Do you have any tips for students starting the application process?
Start now, don’t procrastinate! Applications take time and professors need advance notice to write reference letters. Conversely, you do have to actually submit the application. It is good to be detail oriented, but you must be able to let go.
Morgan Bair Vaughn (Dyer Group) has been awarded a Dean’s Teaching Fellowship for the 2017-2018 school year. The prestigious fellowship provides support to advanced students to allow them to design and teach a course as Instructor of Record while completing their dissertation. Morgan is using this opportunity to teach a section of CHEM 150: Structure and Properties. The course is the first in the core sequence of the new Chemistry Unbound curriculum and replaces “Gen Chem” or CHEM 142. CHEM 150 takes an integrated approach to teaching the chemical disciplines, giving students broad training in chemistry as the foundation of their studies. For instance, Structure and Properties incorporates aspects of Organic Chemistry, normally sequestered in its own course sequence later in the undergraduate career.
Morgan’s research in the Dyer Group focuses on enzymes via the unique method of temperature jump spectroscopy. “My research works to fill in the gaps in our knowledge to allow for the efficient development of new enzymes,” says Morgan. “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.”
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.