Dr. Jonathan Clinger: Leading Innovations in Protein Research

Science is a vast and complicated field with brilliant minds pursuing breakthroughs in many areas. It’s where curiosity and dedication meet to explore the wonders of God’s creation and the complexities of life. Our “On the Road” segment continues with an alum aiming to share and advance human knowledge of proteins. Hosted by Dr. Brad Schultz and Amanda Price, this …. is Mustangs Unbridled.

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Transcript

00;00;00;00 - 00;00;12;04
Speaker 1
Earning a doctorate takes years of study and research coupled with discipline and determination. Even after the degree is earned, learning and research never stops.

00;00;12;06 - 00;00;26;10
Speaker 2
Dr. Jonathan Klinger, Class of 2008, is an assistant professor of biochemistry at Baylor University in Waco, Texas. He has authored or contributed to dozens of publications about proteins. Today we join him in his office. Thank you for having us, Jonathan.

00;00;26;13 - 00;00;27;21
Speaker 3
Yeah, thanks for being here.

00;00;27;23 - 00;00;37;20
Speaker 1
So you've got some strong ties to Lipscomb. Do you mind just elaborating on that? What led you to Lipscomb? What? I said, you start to share your journey with Lipscomb. With us?

00;00;37;22 - 00;00;50;15
Speaker 3
Sure. So my mom's an alum from the late seventies, early eighties. I started in fifth grade at Lipscomb. At the point there was a middle school because my dad was a chemistry professor at the university.

00;00;50;17 - 00;00;53;10
Speaker 2
Did you ever have your dad for chemistry?

00;00;53;12 - 00;00;54;08
Speaker 3
I did.

00;00;54;10 - 00;00;55;12
Speaker 2
How was that?

00;00;55;15 - 00;01;07;00
Speaker 3
Interesting. My solutions are pretty small place, even in the university. And so there's only one person that teaches biochem. So I ended up having him for biochem because that was the only person you could take.

00;01;07;03 - 00;01;09;10
Speaker 2
What did you call him?

00;01;09;12 - 00;01;14;15
Speaker 3
Hmm? Dad. You know, I don't know.

00;01;14;15 - 00;01;18;16
Speaker 1
Probably nothing for him. Olasky Later, Dr. Klinger.

00;01;18;16 - 00;01;28;03
Speaker 3
I don't know. Mostly Dad. I mean, everybody knew it was not one of those things where people didn't know. So what's the point in being weirdly, weirdly formal at everything?

00;01;28;08 - 00;01;37;07
Speaker 1
Well, sometimes when your parents are in something, we take an intensely different path. And didn't seem like that necessarily happened in this case. Or was there a phase of that?

00;01;37;08 - 00;01;55;04
Speaker 3
It was not my plan to become a chemistry major. So I started out undergrad as engineering major, and then I after a semester, I thought, I can't do this. I decided I couldn't be in all my courses the entire time I was in undergrad with that same group of 20 people. I just thought I would go insane taking only engineering courses forever.

00;01;55;08 - 00;02;09;28
Speaker 3
I was. I was bored. And I also had this epiphany that, like the people that I do like or change in, a lot of people I do like or change their major. And so I might as well. I'm not sure I want to do this anyway. I'm a little bored. Let's change the major. I'm not sure I want to do this.

00;02;10;00 - 00;02;28;09
Speaker 3
Then I thought, I want to be a pharmacist. So I go preform a primo. And then I thought that seemed boring. I did want to count pills. So then I didn't know what I want to do after that. And I ended up doing an r U at Vanderbilt, doing undergraduate research for a physics lab, and that meant that experience was good enough.

00;02;28;11 - 00;02;37;03
Speaker 3
I want to go to grad school. So it was a long but not a circuitous route, only change my major once. But I didn't know what I want to do with it for the longest time.

00;02;37;06 - 00;02;49;28
Speaker 2
Your senior year, your teen, your football team won the 2007 state championship under Coach Mack. What are your memories from that? Maybe from playing football or from that season or Coach Mike?

00;02;50;01 - 00;03;05;15
Speaker 3
Yeah. So yeah, so senior year, I mean, not only did we win senior year, we also went every year. I was I played varsity, so we lost in the finals. Sophomore year, lost in the finals. Junior year, one senior year. I want to start out by saying I was not good.

00;03;05;19 - 00;03;06;13
Speaker 2
But you were ahead of the.

00;03;06;13 - 00;03;23;26
Speaker 3
Team. I had the benefit of playing with some very good players, so my teammates were good. They carried me along for the ride, which was very nice of them. I appreciate that and I'll always remember well be 14 year olds. Remember the upperclassmen who were really good and good to me. You know, upperclassmen, team leaders were really good.

00;03;24;00 - 00;03;41;26
Speaker 3
Both my sophomore and junior and I really appreciated that looked up to them. Let's see. Senior year, what was interesting or fun? I mean, we had some very good players. You know, Jeremy Holt was amazing. Russ Moneypenny was really good and Mitchell was good at Mitchell Famous. Now, it's weird.

00;03;41;28 - 00;03;46;15
Speaker 2
Isn't it funny that he was a star athlete and now he's a star country music singer.

00;03;46;22 - 00;04;05;18
Speaker 3
I mean, he always wanted to be a musician. Right. He had the family ties, the music industry. He was always it was really funny in chapel when he went up and imitated Creed sarcastically, and people thought he was really good. Mitchell's a character. But yeah, we had lots of really good players. Some of the games were really interesting.

00;04;05;18 - 00;04;22;14
Speaker 3
I still remember getting thrown like ten yards by Donte Hightower once because I still have like a blue mark on my helmet from when he just picked me up and threw me. So, you know, not not too much though, football wise particularly, but mostly just being around the team and being on the people. And I really loved that set of coaches.

00;04;22;14 - 00;04;24;21
Speaker 3
They were really good, really helpful.

00;04;24;24 - 00;04;39;00
Speaker 2
So a lot of the players that we've talked to that played under Coach Mack, they always they always say, Oh, he said so and so. And everyone has said something different that we've asked, did he have anything that stuck out to you as maybe quirky or.

00;04;39;03 - 00;04;50;08
Speaker 3
There could be an entire there could be an entire humungous, thick, leather bound book of coach mannerisms. One of the ones I still tell my students this to this day is if it itches, scratch it.

00;04;50;11 - 00;04;51;23
Speaker 2
Which means we haven't heard that yet.

00;04;51;27 - 00;05;07;19
Speaker 3
Which which meant like if. If you're doing something, it's not working. Change it. Right. Try to figure it out. Don't keep doing the same thing and just acknowledge that it's not working because you can do better. So if it itches and it's not working, scratch it, try to fix it. And I still don't want students that all the time.

00;05;07;20 - 00;05;13;07
Speaker 3
Like, you can't just keep doing the same thing and assume it's going to change. So you need to try to do something different.

00;05;13;12 - 00;05;16;14
Speaker 1
Led you changing from engineering? It was itching and.

00;05;16;14 - 00;05;17;18
Speaker 2
Pharmacy.

00;05;17;20 - 00;05;18;22
Speaker 1
Head scratching.

00;05;18;24 - 00;05;23;19
Speaker 3
If was not working change. Right? So yeah, but yeah.

00;05;23;22 - 00;05;46;03
Speaker 1
So in a post we read about why you transferred to Baylor University, you're quoted as saying, quote, Excellence in teaching and mentorship. It appealed to you and so reflecting on your experience at Lipscomb, were there teachers that poured into you or coaches mentored you? And are there any that you try to mimic some aspects of that and the relationships you have with your students?

00;05;46;10 - 00;06;12;16
Speaker 3
Yeah, so I really appreciate Coach Hail Chico was the best I had him for both pre cal and calculus. He was very understanding of me being, you know, slightly frustrated in high school and like very understanding always took the time to be like, you know, hey, everything's fine. It's not a big deal. And was really good at getting the best out of me in a time when I was not necessarily the most teacher friendly student.

00;06;12;18 - 00;06;35;15
Speaker 3
And I loved how even keeled he was and how he took the time to deal with students and meet them where they were and not so my way is the my way or the highway, everything. Because, you know, I understand, but I'm a teacher now, right? So like, you know, meeting students where they are and helping to cajole them and bring them along gently was what Chico was really good at.

00;06;35;17 - 00;07;01;14
Speaker 3
And he had like this quiet confidence and quiet, quiet aptitude that was really great. And I really appreciated how he taught calculus and he was excellent. And he was also just a very, very good person. I looked up to him like crazy also. Mr. Sullivan. Mr. Sullivan was great. He was a physics teacher, so he was like the spunky, weird teacher who did crazy things and like, there's nothing better than a physics teacher that's into it.

00;07;01;14 - 00;07;14;18
Speaker 3
We were talking about Newtonian physics, the demonstrations. You can do the things, you can do, the fun you can have in the classrooms, just the best. And he looked up to all of those things, right? You'll see videos on YouTube about, you know, physics professors doing crazy things in the lecture halls. So he did all of those things.

00;07;14;21 - 00;07;15;25
Speaker 2
Like what?

00;07;15;27 - 00;07;35;24
Speaker 3
Oh, when you're talking about conservation of momentum, where you have a bowling ball next to your face and you drop it and it swings on the pendulum and comes back and nearly hits in the face and doesn't. He did that. He did most of the things that you see. You know, we're talking about conservation momentum, where you're talking, you know, any of any of those sorts of like Newtonian physics demonstrations cited by most all of them.

00;07;35;24 - 00;07;44;27
Speaker 3
We also didn't airdrop is a project. Lots of things. Sully was really good about opening people who up to science, who didn't not care about science.

00;07;44;27 - 00;07;49;06
Speaker 1
He'd be a TikTok star today. Maybe there was on video.

00;07;49;08 - 00;08;05;19
Speaker 3
And it isn't, of course, Coach Mac, who was a lovely man and the character I he took the time for everybody, not just the best players on the team. And he was an excellent mentor. And also just being around him every day was great. He was. Yeah, he's special.

00;08;05;22 - 00;08;11;10
Speaker 1
Have you found a way to do that with your students, hoping they have these stories for you one day or.

00;08;11;13 - 00;08;27;01
Speaker 3
I mean, it's I haven't had that many students yet, so we'll see. I had a student in my office just yesterday, actually. He was telling me about a different professor that she was having this relationship with because, you know, she was just like he was really frustrated with her for not getting it. She also works as the research lab.

00;08;27;03 - 00;08;43;11
Speaker 3
It was like, you know, I'm just like your dad. But this is really frustrating to me that I cannot get you to understand. It's like working at the dining room table at home. I can't get you to understand this chemistry, and you're frustrated and I'm frustrated. We're both frustrated because they just have this relationship. And, you know, I, I fully intend on having that relationship with people.

00;08;43;11 - 00;08;56;03
Speaker 3
I think I'm building that with people in my lab. But I've only been here two years. Right. And so there's sort of limited things you can do with that amount of time. For my students, the door is always open. You're always welcome to come in and, you know, shoot the breeze with me or come in and ask for help.

00;08;56;03 - 00;09;02;20
Speaker 3
And I really try to be open and available to my students. And also I try to be patient, not always the best, but I try to be patient.

00;09;02;22 - 00;09;06;24
Speaker 2
So speaking of Chieko, did you know that the baseball team honored him in February?

00;09;06;24 - 00;09;07;25
Speaker 3
I did not realize that.

00;09;07;25 - 00;09;19;06
Speaker 2
Yeah, they're going to put up a plaque for Coach Smith and Chico. They're at the dugout to honor Gogo and how he was faithful for 30 years.

00;09;19;08 - 00;09;20;15
Speaker 1
And at least I think it's maybe.

00;09;20;15 - 00;09;21;07
Speaker 2
40 or.

00;09;21;10 - 00;09;22;20
Speaker 1
40, 45 to 40.

00;09;22;20 - 00;09;23;14
Speaker 3
Sounds right to.

00;09;23;14 - 00;09;23;23
Speaker 1
Me.

00;09;23;23 - 00;09;25;22
Speaker 3
To Chico was the best.

00;09;25;25 - 00;09;34;01
Speaker 2
Before we move forward, I just noticed your coaster. Is that a smart coaster? Because I saw a light to keep it. What did you see?

00;09;34;01 - 00;09;39;02
Speaker 1
That I got my mom. One of those for Mother's Day last year because she was always complaining her coffee was cold.

00;09;39;02 - 00;09;40;21
Speaker 2
So that is the same.

00;09;40;21 - 00;09;55;16
Speaker 3
You know, they're so nice. I would never about this for myself. My brother bought it for me and I use it every day. It's it's great. It allows me to go make coffee and then go teach and leave it half full. And it still, when I get back to it.

00;09;55;18 - 00;10;10;23
Speaker 1
So your dad is from Fort Worth and then you mentioned you came to Lipscomb in fifth grade. So you did end up back in Texas at a couple of different takes. It Texas Institute. Was that a coincidence or was there something about Texas that drew you back?

00;10;10;26 - 00;10;27;26
Speaker 3
It was yes and no. I don't know. The first time when I went to Rice, it was most for my Ph.D. It was mostly coincidence. I had applied to a bunch of schools. I was comfortable going to Houston because my grandparents had lived in Houston as a small child. My dad was, of course, from Dallas originally and I was coming up with Houston.

00;10;27;26 - 00;10;46;23
Speaker 3
But it's not like I was planning on coming here. I applied to North Carolina and Duke and UAB and Vandy and Rice and Cornell and a bunch of places, and I sort of always assumed I didn't have a family. And then Rice really wanted me advantages as you I was going to come, and that made a difference to me.

00;10;46;26 - 00;11;02;07
Speaker 3
And so Rice was the right spot for me to go in. So it was not get back to get to Texas sort of thing. It was this this feels like the right spot. It was really sort of organic and I wasn't going to Texas was not a downside, but it wasn't upside either really for me the first time.

00;11;02;09 - 00;11;21;07
Speaker 3
And then coming back to Baylor, Texas, was a draw. So I met my wife in Houston. We both have tons of friends in Houston. We did not like upstate New York nearly as much. It was sort of like coming to Baylor, even though we've never lived in Waco before, was like coming home because we're not. We're close to friends and people we know from.

00;11;21;10 - 00;11;28;04
Speaker 3
You know, when I was in grad school and she was a young teacher and it's like our found families in Houston, so it was great to come back to them.

00;11;28;07 - 00;11;39;21
Speaker 1
So we just mentioned we were many were the archivist is also kind of grad as well. And she mentioned that Waco reminds her of Nashville like 20 years ago.

00;11;39;24 - 00;11;57;00
Speaker 3
That is maybe fair. It it does feel more like my childhood in Nashville in a bunch of ways than Nashville does now. When I go back to Nashville now, I'm like, Why are there so many people? Why, you know, And my dad, you know, still drives Lipscomb from New York every day. And he says, you know, it used to be 20 minutes.

00;11;57;00 - 00;12;18;16
Speaker 3
Now it's like an hour. And I I'm driving a similar ish distance to Baylor every day and it's 15 minutes. So it probably is. Yeah, sort of more. But I don't have a good frame of reference because of, you know, when I was a child, I, we didn't go into downtown all the time. Right. Only occasionally. I do think that Waco is a lot better than it used to be.

00;12;18;16 - 00;12;35;21
Speaker 3
I've heard terrible stories about how Waco was the school, and nothing in Waco was like a terrible place to be. And Baylor was the only thing here. It's not that way anymore. All right. And which is really nice. I it's a much better place to live. And I think it used to be and I'm really happy with the size and all of that.

00;12;35;21 - 00;12;37;15
Speaker 3
It's nice.

00;12;37;17 - 00;12;42;27
Speaker 2
I checked your yearbook and I looked at your senior quote. Do you remember what you put?

00;12;42;29 - 00;12;44;06
Speaker 3
I have no idea.

00;12;44;09 - 00;12;52;06
Speaker 2
So this is a good one. It's better to remain silent and be thought a fool than to open your mouth and remove all doubt. Abraham Lincoln.

00;12;52;08 - 00;13;03;01
Speaker 3
Yeah. So I was really, you know, in high school in some ways, I guess, because I talk a lot now. Well, I'm bringing a shy, I don't know, but I.

00;13;03;04 - 00;13;27;29
Speaker 2
Yeah, well, Brad and I are going to remain a little silent on this next part so we don't reveal anything about us. But I want to talk a little bit about your career. Sure. You received a doctorate in molecular biophysics from Rice, and your research has focused on the dynamics of proteins. So can you give us a, you know, high view of your studies?

00;13;28;02 - 00;13;47;21
Speaker 3
Yeah. So in order to keep us and every living thing running, there's proteins in our bodies to do chemistry. They also for use lots of other functions, you know, structural carrying of ligands and compounds. Right. Like getting all of our oxygen from our lungs are the antibody proteins do that right, because that's, that's what my hemoglobin do. Right.

00;13;47;23 - 00;14;11;08
Speaker 3
And in order for us to you know since light that's what we're Dobson does it senses light photons and what I care about are enzymes so enzymes are proteins that do chemical reactions to keep our body running. And in particular, I'm interested in metabolic enzymes. These are the enzymes that are just like housekeeping all the time, keep our cells growing and alive and happy.

00;14;11;10 - 00;14;27;12
Speaker 3
And so underneath. So what these enzymes do is they take one chemical compound and convert it to another chemical compound. And so when they do that, there's a chemical reaction that takes place and then they use whatever. And there's a reason why they have too much of one thing when you make more of something else. And so they convert it.

00;14;27;15 - 00;14;46;03
Speaker 3
And each protein is very specific, each enzyme very specific for its substrate, and it converted to some very specific product. And it all goes along the way and it's what it does. The function of this enzyme is determined by a sequence in its structure. And so I study the structure of these enzymes. I want to know what they look like.

00;14;46;05 - 00;15;07;25
Speaker 3
And so in my lab, we do experiments to figure out what proteins look like, what they do, how they perform, the chemical reactions, what interactions are they making with our substrates and products, how are they doing what they do every day in the cell or every moment in the cell, actually. So we do. We use a bunch of physical tools to understand what they do, basically.

00;15;07;28 - 00;15;19;04
Speaker 3
So my lab does X-ray crystallography and chromium, which are structural characterization and metrics to see where the atoms are in proteins. That's really what we do. We look at atoms all day long.

00;15;19;07 - 00;15;32;19
Speaker 2
Well, after rice, you talked briefly, you went to Cornell and I saw that you developed what's called a millisecond mixing quench, which is why Bailer wanted you here. Can you tell us what is that method?

00;15;32;21 - 00;15;49;22
Speaker 3
Yeah. So normally people study enzymes, statically they get these off a structure and they say this is the structure of the enzyme, but you can't really want to do it's reaction if you solve a structure of it. Right? So you need what you would really like to have, You'd like to have a movie of the enzyme doing the reaction, right?

00;15;49;22 - 00;16;09;01
Speaker 3
You'd like that multiple states have it bind the substrate, have it do the catalysis, have it, release the product, be able to watch that function. Right. Because enzymes are dynamic, they move. And so typically how you would do this is it takes lots and lots and lots of protein. So you would need like some number of grams of protein.

00;16;09;01 - 00;16;28;03
Speaker 3
Grams does not sound like much, but grams when you make it, when you have E coli or yeast or something that makes your enzyme for you, grams is like an extreme amount. So like one expression that would take you like a day if you use a liter of sample might make a milligram of protein pure once you purified it.

00;16;28;05 - 00;16;48;19
Speaker 3
So you need do this a thousand times or do a thousand liters in order to make enough protein to do your experiment. This is a nightmare, right? So like when I was a graduate student and we were doing these kind of experiments where you would need a gram of protein, and I would we're working on a photoreceptor, so I would spend six months in the dark making my sample for a one week experiment.

00;16;48;22 - 00;17;06;22
Speaker 3
That was no fun. I didn't want that to be my life in my graduate students life forever. And so when I went to Cornell, I developed a technique to use to do the same experiment, but with no grams of protein. So one expression you can do these experiments instead of spending six months of your life making your sample for one experiment.

00;17;06;24 - 00;17;28;21
Speaker 3
And so this and not only does it allow us to make use way less sample in only just way less simple means it's easier for the graduate student or the post-doc, whoever is actually doing the project. But it also means you can study things that are harder to make, right? So normally that you always people only say things that are easy to make because you can't make the stuff it's hard to make in an off quality period, like use can't be done.

00;17;28;23 - 00;17;51;07
Speaker 3
So we can actually work on our targets now because we need so much less of our sample in order to do our experiment. It also means that instrument time at the places you do these experiments, which is all national labs, there's not that many of them the world. It's much easier to get with our method because instead of So how this normally works, why it takes so much less sample is because normally you put x rays through your sample.

00;17;51;07 - 00;18;05;21
Speaker 3
When you ruin it, you throw it away. You have to do it to the next bit of sample. All right. In order to do that in your time is changing all the time. You're doing all this, the room temperature. And so in order to get time points, you have to measure a crystal, throw it away, grab another crystal measure, throw it away.

00;18;05;24 - 00;18;26;04
Speaker 3
Just keep grabbing new protein and throwing it away all the time. You need to do this tens of hundreds of thousands of times. So that's why it takes grams with my technique millisecond mixing, which we can with millisecond time resolution, stop the reaction by throwing it liquid nitrogen. And so we can stop the reaction with cryo and then we can measure it at our leisure.

00;18;26;04 - 00;18;43;25
Speaker 3
We can measure it as slow as we want. We can get all the data from one crystal instead of getting a tiny bit of data from tens of thousands of crystals each. So it greatly lowers the amount of lowers the burden on doing these timer's all the experiments because previously you could do them. They were just extremely hard and they're like five places in the world.

00;18;43;25 - 00;19;01;26
Speaker 3
You can do them now, we can do them now. We can make enough protein for doing them pretty easily. You know, I've got graduate students who, like over the course of a week, make plenty of protein to work for months, and then we can collect data at many more places than you can do. The more, the more challenging experiment.

00;19;01;29 - 00;19;03;09
Speaker 2
How do you make protein in the lab?

00;19;03;16 - 00;19;27;16
Speaker 3
We put some DNA in E.coli and we ask that you call it very nicely to make protein for us. Yeah. So basically we put a circular DNA called PLASMID. We transform it into e coli in the plasma, has some instructions on it, has instructions for how our sequence for a protein. It also has an antibiotic resistance gene, which is a reason for the you to keep the circular piece of DNA.

00;19;27;19 - 00;19;48;04
Speaker 3
And it also has a thing upstream of the protein called promoter sequence, which says, you know, if I add something, please start making protein now. And so we, we transform our E.coli with our plasmid. We make sure the plasmid in there, it looks good. We grow leaders of E.coli in flasks, and then we add a chemical that says, please make our protein.

00;19;48;04 - 00;20;01;12
Speaker 3
Now E coli, then make our protein. And when they're done, we spin them all down for the appellate reason, spin them in buffer, crack them open, pull our protein out of a mix.

00;20;01;14 - 00;20;04;20
Speaker 2
So what I would have assumed.

00;20;04;22 - 00;20;12;05
Speaker 1
So has the has the millisecond mix and clinches it made the other technique obsolete, or is it or is there still some reason some people would choose.

00;20;12;05 - 00;20;30;16
Speaker 3
That it is complementary? So there are reasons why you would not prefer to do the millisecond makes sense because we are freezing our sample, which means we are changing it in some way. Which means that, you know, we are perturbing our sample. So if you wanted like it also lowers the time resolution a little bit because it takes 5 milliseconds or something to cool.

00;20;30;23 - 00;20;50;19
Speaker 3
And so we can never be quite as fast as the room temperature methods. Also, we are perturbing our sample, we call it. It's really important to consider that and people don't consider that nearly as much as they should, but you should consider that. And finally, there are certain things that are so sensitive to X-rays that it would be really hard to observe intermediates with our method.

00;20;50;22 - 00;21;11;14
Speaker 3
And so if you have radiation image problems or if you really want or if you want to go slightly faster than if you want a microsecond or faster, those are the two reasons why you really would need to do serial still, which is the other kind of method. It's called Serial because you're throwing a new crystal and all the time you have them, like in the serial pipeline basically where you're constantly throwing new crystals in a jet at the X-ray beam.

00;21;11;17 - 00;21;13;23
Speaker 2
Is this technique patented?

00;21;13;25 - 00;21;14;22
Speaker 3
No, it's not patterns.

00;21;14;22 - 00;21;16;27
Speaker 2
So everybody in the labs are using it now.

00;21;17;02 - 00;21;35;24
Speaker 3
A couple of labs are using it now. Yeah. So we develop the technique and I think parts of it are patent pending. But there's a bunch of ways to do what we did until other people were know. Other places are working on similar, similar sorts of experiments. So there's a group in Germany that I started presenting at meetings.

00;21;35;24 - 00;21;37;13
Speaker 3
I said, Oh, this is great, and they immediately copied it.

00;21;37;20 - 00;21;39;09
Speaker 2
Do they call it the Klingon mix and?

00;21;39;09 - 00;21;48;03
Speaker 3
Quint No, they did not. I don't think. I don't think my post-doc boss would have appreciated that.

00;21;48;05 - 00;22;11;29
Speaker 1
So Amanda mentioned that this technique is one thing that drew our guest Baylor, in her interest in you, but you also came to Baylor in support of a $2 million cancer prevention research award. So I guess your lab focuses on enzyme behavior in the context of cancer research. So what led you to want to, I guess, focus? I would say all your research on that, but maybe it is, But that will be a focused area for you.

00;22;12;01 - 00;22;31;17
Speaker 3
Yeah. So I really want to know how enzymes do their chemistry and turns out enzyme chemistry is really important. Lots of cancers. And so it was me being drawn to it in like previously in my career I've been doing methods development mostly right? I've developed techniques to understand how enzymes work. And now the question was, okay, I don't want to give up taking some.

00;22;31;17 - 00;22;54;17
Speaker 3
We want to actually do some do, some do some biochemistry and the obvious thing to me was start working on these metabolic enzymes. All right? So cancer's really important. Metabolism is really important cancer, right? So cancer has a very fast metabolism. It grows rapidly. And so I what I'm interested in is how how do these metabolic enzymes, these enzymes that speed growth, how do they work, how are they controlled?

00;22;54;19 - 00;23;17;05
Speaker 3
Can we design inhibitors for them? And it turns out they're all have they're all really upregulated in cancer. They're also surprisingly challenging design inhibitors for some of them because they're just dynamic, they're mobile. And so we're trying to understand like how their mobility and how their catalysis contributes to their mechanism and then hopefully design inhibitors that will hopefully help cancer down the road.

00;23;17;07 - 00;23;22;29
Speaker 1
Have you had any discoveries, revelations in your research already, or is it so early on?

00;23;23;01 - 00;23;49;20
Speaker 3
Oh gosh, I've been here less than two years and my labs only been open for one of those. So we're early days here. The the the road to a drug is long. So, you know, as a stretch goal. And some of my students Ph.D. projects these take six years is maybe we'll start looking at considering designing a drug candidate you know a lead compound, so to speak.

00;23;49;23 - 00;24;18;00
Speaker 3
All right So once once you get a lead compound, then it's like that. People are willing then you have to do animal models. And then after animal models, you have to do trials. The we're like one in five years from anything that in my lab could possibly come out it. So it's just it's a long road to do drug design and one of my first graduate students when do I get to solve cancer was like you eventually hopefully she was she was sad about that.

00;24;18;00 - 00;24;28;28
Speaker 3
But I think she understands now, like how big a lift any any of these techniques are. And then we'll get but she's made lots of progress. She might get to designing a lead compound by the time she defends. Maybe.

00;24;29;01 - 00;24;38;14
Speaker 1
But have you been able to use A.I. to help with anything you're doing? And that's the hot topic everybody's trying to insert into everything right now. So yeah.

00;24;38;17 - 00;25;14;26
Speaker 3
So we are at the precipice of becoming a huge deal in my field. So there are drug companies that are using AI in their drug design efforts. It's sort of at the moment just beyond the reach of general practitioners. And so you may or may not have heard of Alpha fold. Alpha Fold came out of Google in 2021 and it's this program, the software that will if you give it a protein amino acid sequence, it will tell you what your believes your structure should be, which immediately caused a huge stir in the field.

00;25;14;26 - 00;25;32;00
Speaker 3
Because if you're somebody like me who studies what the structure is, you know, you start question, Do I have a job anymore? And the truth is it's not that good yet. And it also does know has no way of telling you dynamics. But all this sort of stuff is coming. The real the current looming factor is good training data.

00;25;32;03 - 00;25;46;07
Speaker 3
So you need to be in order for your artificial intelligence model to do a good job, you have to be trained on something. Right? And so this is the problem which at GPT currently what it's still buggy is turns out there's not enough data on the internet to train. It is like as well as you would like it to be, you know, they still do amazing things.

00;25;46;07 - 00;26;09;26
Speaker 3
They still elucidate and still have issues, right? And all that sort of stuff. The reason why Alphabet works is because the training set was perfect. That training still not perfect, but training set was very good because the protein databank has hundreds of thousands of structures in it of 60,000 or something different proteins. And it and because of the structural genomics projects and 2000s and 20 tens, the training set is really, really good.

00;26;09;29 - 00;26;27;13
Speaker 3
There's not a fault in nature. We have an observer, at least we don't think there is. And so that's what makes our full work if we've observed all the folds. So now it has a really good way of guessing what things look like. So for static structures, that works pretty well. There are corner cases where it doesn't, it still screws up, but like it works pretty well.

00;26;27;15 - 00;26;59;09
Speaker 3
And next I think is going to be a guy from molecular organic simulations. And so trying to get at the dynamics point of view, it's just having a static structure. And so that's coming next. I think that'll be probably working in five or ten years in some capacity. What makes more dynamic simulations hard is you have to calculate all the forces on the protein at any given moment, recalculate the momentums, let it move for a femtosecond, and do this process again iteratively, which means that it's really hard to simulate long timescales like milliseconds.

00;26;59;12 - 00;27;20;03
Speaker 3
So milliseconds in proteins is a long time scale, and that's what that's the room I study experimentally. And the reason why I study the experimentally is you can't get there with simulation very easily. And so in 10 to 15 years it might be possible for AI to sort of start stepping in, bridging that gap between picosecond nanosecond simulations and millisecond simulations.

00;27;20;05 - 00;27;45;00
Speaker 3
Now the idea is it's really better because instead of having to reconstruct all the forces every time step, you can instead compute the forces a couple of times. Let the I guess them iteratively after that, which should be faster than actually I would compute using Hooke's Law. In other, you know, physics parameters what all the bond lengths and angles should be and how their momenta of every atom should be.

00;27;45;02 - 00;28;32;25
Speaker 3
So that's coming next. Already drug companies are putting A.I. in their docking platforms and their virtual screen drug design platforms. People are interested in using that for academically too. And there's a couple of papers from the last year or two saying we get huge uplift with virtual screening, with AI. So virtual screening is this pipeline where you take a billion compounds that are small molecule organic compounds like drug candidate type looking things and you have them, you basically though your protein in and then you just asked, does each of these things bind to my protein iteratively for the billion compounds, this takes like a month on an Amazon web server cranking off.

00;28;32;25 - 00;28;53;06
Speaker 3
So it costs like if you look at Amazon Web server costs like $20,000 and takes a month to talk. This billion compounds. People are currently claiming they get fairly large uplift by using A.I. to do something similar. So you take a small subset of the billion compounds, say million compounds, which takes, you know, instead of a month, it takes a day and a half.

00;28;53;08 - 00;29;13;01
Speaker 3
And then you say, okay, this is my training set, and you train your A.I., you have your A.I. trained on that, and then guess the rest of them and people are claiming huge uplift. I'm I haven't done it yet personally. We're going to try it probably. So it's possible that is going to make everything faster in all kinds of different ways, starting with drug design.

00;29;13;03 - 00;29;21;06
Speaker 3
I think that is becoming a bigger deal and it's something that everybody needs to know about, but it's not replacing experimental as yet right?

00;29;21;08 - 00;29;33;18
Speaker 1
So when we came in, you were talking about the growth of guests of chemistry at Baylor. In the end, I'm guessing that's due to interest. I mean, most growth is due to interest from students, correct? Or is there something there beyond that?

00;29;33;20 - 00;29;55;05
Speaker 3
I mean, it is a combination of things, right? So Baylor has very recently became our one. They're very excited about doing scientific research especially, but all research, Baylor is really interested in growing the research, the research output of the university, and they've made lots of good hires that have helped attract people. The chemistry graduate program has grown a ton.

00;29;55;05 - 00;30;13;09
Speaker 3
It's been growing since I've been here, but it's been growing a lot over the past 10 to 15 years as we've made some very good hires of very well-respected chemists who've come in and make Baylor a much better research university. That was before, I shouldn't say just chemists. There's also been other good people in the department, so I'm just I'm the chemist, so I know the chemistry better.

00;30;13;12 - 00;30;17;09
Speaker 2
But we are in a massive building that is a science.

00;30;17;09 - 00;30;20;01
Speaker 3
Dedicated it. Yes. Yes. And we're outgrowing it.

00;30;20;06 - 00;30;23;08
Speaker 2
So is this the biggest building on campus?

00;30;23;11 - 00;30;30;12
Speaker 3
I think it is the biggest academic building on campus. So you're say, academic because of course athletics the field out. Yeah. You know.

00;30;30;14 - 00;30;42;12
Speaker 2
So then are the sciences is that like the largest of your student body? Is that the largest interest discipline?

00;30;42;14 - 00;30;48;06
Speaker 3
I think biology has more majors than anybody else. I think in chemistry it's like fourth or fifth with the.

00;30;48;06 - 00;30;50;21
Speaker 1
Sciences are leading the way in a universe at.

00;30;50;22 - 00;44;15;18
Speaker 3
The.