Broadly, we in the Buller lab study enzymes, the little molecular machines inside our body (and all living things) that do chemical reactions. Our goal is to better understand these enzymes and figure out ways to make them more useful to the scientific community and society as a whole. Some enzymes (as shown below) are already ubiquitous in our lives, and we might not even realize it!
Chemistry powers life. Many of the sights, smells, flavors, and feelings we know as humans are the result of chemicals that have been made by enzymes. These chemicals are broadly called “natural products,” and they inspire chemists to develop medicines, materials, and other chemicals with valuable properties. A well-known example of this is the pain-relieving qualities of willow bark, which was subsequently discovered to be due to a molecule inside the bark, leading to aspirin!
Do you like food? Enzymes are also responsible for the chemicals that create flavors. Below are the structures of molecules responsible for the flavors/smells of vanilla and lavender. Each of these flavor molecules is the products of numerous enzymes acting in assembly-line fashion to make the final product. Consider all the flavors and smells you are familiar with. There is likely a molecule or concoction of molecules that is responsible for each one! There is incredible diversity in the kinds of molecules that enzymes can make, much of which is not yet fully known.
Another example more relevant to the Buller Lab is serotonin. This is considered the “happy chemical” that our body produces (via enzymes) as a signal in our brain. The core structure of serotonin has inspired many important medicines to treat symptoms such as migraines, headaches, and depression. This and other ‘medicinal building blocks’ can be made by enzymes we have developed in our lab.
One of the most valuable features of enzymes are the way that they are made. Every living cell on the planet neatly contains the blueprints for every one of its enzymes in its DNA. Over the past few decades, the scientific community has become extremely efficient at manipulating DNA in various ways. As a result, we now have the ability change the instructions encoded in DNA. Since DNA encodes for enzymes, this means we can ‘engineer’ enzyme by modifying DNA. Currently, we work with enzymes that come from sperm whales, flowering plants, watermelon, fungi, and numerous bacteria. We make these enzymes using a safe and easy to work with laboratory form of E. coli. As a result, the enzymes we work with are simple for any scientist or industry to get their hands on!
Often, the enzymes that we work with are well-suited to do the job they do in nature, but considerably less good at doing some of the other jobs we wish them to do. This requires us to figure out ways to make them better. We can make a series of small changes to enzymes by changing their DNA blueprint.
We then test each enzyme to see if it has improved at doing its job. We then pick the enzyme that performs the best, and continue to make small changes, to see if we can make it even better. This process is called directed evolution, and this technique was awarded the Nobel Prize in 2018. It is similar to the process of natural evolution and concept of “survival of the fittest.” In the lab, however, we speed up this process and customize the “fitness” that we, as researchers, are interested in.
Along the way, we often notice that a particular enzyme is doing something that we find interesting, such as changing color or making a new material. In these instances, we often choose to sniff out what’s going on by studying the enzyme further. This brings us to the field of enzymology – the study of enzymes and their mechanisms. The tools and techniques that are used to study enzymes are wide-ranging and of varying complexity. In each case, studying enzymes allows us to make sense of the world around us, and figure out ways to harness the power of enzymes more effectively.