Introducción: 
Welcome to the Salk Institute’s Where Cures Begin podcast. Where scientists talk about breakthrough discoveries with your hosts, Allie Akmal and Brittany Fair.

Brittany Fair:
I’m here today with Dmitry Lyumkis. He is an assistant professor in the laboratory of genetics, where he uses high-powered imaging techniques to determine the structure of tiny molecules. Understanding what these assemblies of atoms look like, could reveal dysfunctions that lead to disease. Professor Lyumkis, welcome to Donde las curas comienzan.

Dmitry Lyumkis: 
Hi Brittany. Thank you very much for having me.

Brittany Fair: 
Thank you for joining us today and just kind of to start out, where are you originally from?

Dmitry Lyumkis:
I am from Riga. It’s the city of Riga in what is now Latvia. It used to be [part of] the Soviet Union. We moved out from Latvia about one month prior to the collapse and we came to the Bay Area. I was only six [years old] at the time. My dad is a physicist and like many other people from the former Soviet Union who had a background in physics and mathematics, they were heavily recruited into the United States, Western Europe and other countries. And so at that time in the Bay Area, there was rapid development in the high-tech industry. And my dad was one of those [people] who were recruited.

Brittany Fair: 
When you’re coming from the Soviet Union to the Bay Area, I can imagine that was a very dramatic change for you as a young child. Did you have any challenges when you first arrived in California?

Dmitry Lyumkis: 
Yes, there was definitely a few challenges when I arrived. I didn’t know the language and it took me a few months to learn the language. It’s a little bit simpler when you’re a kid, but it took me a few months to learn the language. And then, what I fondly remember was the social interactions being very difficult and a little bit awkward because I didn’t know how to express myself when I went into school and kids didn’t understand me. And actually one of my best friends, my best friend to this very day, he kind of guided me along that whole process and helped me out quite a bit in those first few months. To this day, we laugh about it.

Brittany Fair: 
That’s great. And what a good friend to have because I’m sure that was a cultural shock. Your dad was then working in science or as an engineer in science?

Dmitry Lyumkis: 
He was more of an engineer. He was working in academic research in the Soviet Union very shortly prior to the collapse. A lot of those jobs started to disappear. So then, when my dad moved to the Bay Area, he started working as an engineer in the industry. And he basically gave us a new life and new opportunity here.

Brittany Fair: 
And did you have an interest in engineering at any point or when did you really become interested in science?

Dmitry Lyumkis: 
I had a lot of interests when I was growing up [laughter].

Brittany Fair: 
Yes? [laugh].

Dmitry Lyumkis: 
I went through many different thoughts in terms of what I would do for a career. My real passion for science came in college when I actually started working in a research lab, that’s when I became really interested. Over the course of sophomore, junior and senior year was when I really became interested in chemistry. There are thousands and thousands of different reactions and many possible ways to arrive at a result. And the idea of sort of developing your own path toward arriving at this complex molecule was really attractive to me.

Brittany Fair: 
I think that’s really interesting because it’s not every day where someone is studying something with such a passion that they’re not able to see.

Dmitry Lyumkis:
Right. I agree. My interest began in chemistry, but soon afterwards I became really interested in specifically protein chemistry or protein structure, a field that we refer to as structural biology. Proteins are made up of amino acids, long chains of amino acids. And they fold into complex three-dimensional shapes and their function are governed by specific chemical reactions, for example, within the active site of the enzyme. And actually that’s a field that I continue to study and work in to this day, which continues to fascinate me.

Brittany Fair: 
Okay. And when you say that you’re studying how proteins are assembled, what techniques do you use to study that?

Dmitry Lyumkis:
We use a technique called cryo-electron microscopy.

Voz en off: 
Cryo-electron microscopy also known as cryo-EM uses frozen samples, hence the word cryo, and gentler electron beams than traditional electron microscopy to examine biological samples.

Dmitry Lyumkis: 
We routinely apply cryo-electron microscopy to determine the structure of proteins and protein assemblies. It’s a microscopy technique that uses high-energy electrons to image objects at very high magnification. So typically, atomic or close to atomic level.

Brittany Fair: 
Oh wow. So you actually are able to see these tiny assemblies.

Dmitry Lyumkis: 
Oh yes. Yes, absolutely. And the resolution can be or is approaching atomic-level resolution. In fact, there were a few papers, manuscripts and preprints, that came out on bioRxiv just a few months ago, which show that you can use cryo-EM techniques to image proteins at true atomic resolution.

Brittany Fair: 
Okay. So you can use this imaging technique to then understand the structure of these molecules, but how does understanding the structure aid you in deciphering the function?

Dmitry Lyumkis: 
Well, seeing is believing [laugh]. A picture’s worth a thousand words. And I’ll give you one example from our recent work where we used cryo-EM to visualize how a specific class of small molecules interact with and bind to a protein assembly that we’re interested in. We found that these small molecules bind in a completely different way than we previously expected. There wasn’t a way to really predict this using any other techniques. So we had to actually get an image, a direct three-dimensional representation, to really understand and to have this “aha” moment.

Brittany Fair: 
What was it like the first time that you actually used cryo-EM to visualize a structure that you were studying?

Dmitry Lyumkis: 
Oh, it’s amazing. That’s one of the coolest parts about the field is that you can purify a protein or protein assembly that is nanometers in size. You can purify them and you can put them onto a three-millimeter support grid, put it into the electron microscope and then come out with images of these assemblies that can lead to three-dimensional representations that are very informative.

Brittany Fair: 
So you came to UCSD for undergrad, went to graduate school at Scripps and then started your academic career as a Salk fellow. What made you want to stay on at Salk and become an assistant professor?

Dmitry Lyumkis: 
Salk is a very interesting place. It’s a very inspiring place. Every single one of my colleagues is a leader in their own respective fields. The people here are really some of the best scientists in the world and they inspire you on a daily basis.

Brittany Fair: 
Have you been able to collaborate with people outside of your field at Salk?

Dmitry Lyumkis: 
Yes. Salk is one of those interesting places where all of the faculty on the one hand, have their own individual island of research, but on the other hand, there are very deep interconnections in the ideas between different labs. And so, there are a lot of opportunities to establish scientific connections and forge collaborations between different labs based on common interests.

Brittany Fair: 
And while at Salk, several of your discoveries have involved imaging tiny structures that help HIV infect cells. What really interests you about HIV and how is imaging these structures going to possibly help with the developments of a treatment?

Dmitry Lyumkis: 
HIV is one of the most complicated viruses that we’ve known about. One of the things that we’ve done is used cryo-EM to image protein assemblies that are directly responsible for establishing a permanent viral infection in a specific target cell. We described how these assemblies are put together, how they look and how they function at an atomic level. But what’s important is that these assemblies are also the direct targets of one of the most important classes of drugs that are used in antiretroviral therapy to treat patients.

Brittany Fair: 
Were these drugs in use to treat HIV and we just didn’t know how they were fully working on a molecular level?

Dmitry Lyumkis: 
Yes. So these drugs have been in use since about 2007 and some of the latest generation ones have been in use [for] about seven years now. They’ve been approved by the FDA. We are working with a team of investigators at the NIH to develop sort of third-generation drugs that will be active and potent against the virus when it evolves resistance. And what we found in this recent paper is that these compounds bind in a completely different way from what we expected previously. And that has important implications because in order to understand how these drugs bind, how to make better compounds and understand how the virus evolves resistance, you really have to know at a detailed atomic level how these compounds bind and how they interact with these protein assemblies.

Brittany Fair: 
Since the coronavirus pandemic, have you incorporated any coronavirus research into your own work?

Dmitry Lyumkis: 
Yes. We have one particular project that’s going on in the lab. And again, it has to do with understanding how a particular protein that is part of SARS-CoV-2 is assembled and specifically how it binds to and hijacks cellular machinery to then promote viral infection. And so, what we’re trying to do right now is to image this protein.

Brittany Fair: 
Okay. Do you think this type of work could help inform treatment options?

Dmitry Lyumkis: 
Yes, definitely. Understanding how viral proteins interact with host proteins can have important consequences and important implications because if you can understand how they interact with one another, then you can potentially develop therapeutic strategies that will interfere with that interaction. And if that interaction is necessary for viral infectivity, then interfering with that interaction will in turn have therapeutic benefits.

Brittany Fair: 
So it sounds like in college is when you really fell in love with science. Prior to college, what did you envision doing in the future? Did you ever consider another career?

Dmitry Lyumkis: 
I’ve always liked to learn and I’ve always liked the process of learning and potentially discovering. So when I started [working in] science, it was kind of a very logical career choice for me because every single day you learn something new. You don’t discover new things [laugh]. That happens very rarely, but when it does happen, it’s amazing. But every single day you learn something new. Science was kind of—it was a natural choice and I’ve never looked back.

Brittany Fair: 
What’s your favorite part about being a scientist?

Dmitry Lyumkis:
It’s the process and it’s the fact that every single day I am learning something new. Every single day, I have a little bit of a better understanding of some small part of our research or some small aspect of a problem. Once you’ve reached one goal, then the next goal is around the corner.

Brittany Fair:
It sounds like never-ending academic growth. What is your next step?

Dmitry Lyumkis: 
Well, there are a number of important molecules and important processes in the cell that we would like to understand at the molecular level. So what we’re trying to do right now is isolate and purify certain types of protein assemblies that are important, not only in virology, but also have important implications in cancer so that we can start imaging them using cryo-EM.

In the long term, I want to see these molecules in cells. Right now, everything that we’re doing is isolating these molecules from cells. I want to visualize them in cells, in their native environment. I think that’s the next order of complexity that is just around the corner that we’d like to understand.

Brittany Fair:
Thank you so much for joining us on the podcast today, Dr. Lyumkis. It was a pleasure speaking with you and learning about your work here at Salk.

Dmitry Lyumkis: 
Thank you very much, Brittany. It has been a pleasure to speak with you.

Fin: 
Join us next time for more cutting-edge Salk science. At Salk, world-renowned scientists work together to explore big, bold ideas from cancer to Alzheimer’s, aging to climate change. Where Cures Begin is a production of the Salk Institute’s Office of Communications. To learn more about the research discussed today, visit salk.edu/podcasts.