Natalie Kuldell (00:02):
You were my student back at MIT when we started BE and you were in 20.109, which we’ll, we’ll go back to and part of the iGEM team, but what are you doing now? And, and yeah. What have you done, you know, between MIT and now?
Stephen Payne (00:19):
Oh, okay. So yes I’ll, I’ll start from the beginning. So, you know, in large part, because of, of, you know, being B as well as doing IgM obviously was interested in synthetic biology, wanted to continue that in grad school. And I went to Lingchong You’s lab down at Duke and there, I really studied sort of mathematical modeling of a synthetic biological system. So I felt, you know, from, from IgM and some of the other projects, you know, we learned a lot of quantitative tools, but we weren’t really applying them as much. So you know, basically trying to mathematical model, different spatial patterns and was able to engineer a system of positive and negative feedback loops with diffusible molecules to make patterns of space and developed a stochastic agent based model for that. So that was pretty cool.
Natalie Kuldell (01:31):
That’s like, that’s like a goal, right? Like that that’s been one of those things that people have been working towards. It’s really hard.
Stephen Payne (01:40):
Oh yeah. Like I was in my third or fourth year and I was looking at what maybe more like second or third. And I was like, I don’t know if this is going to work. Like it doesn’t seem like it’s going that well. And then I made some tweaks to the system and basically started to see, you know, different phases occur in a, a plane. And then that gave me hope. And then I, I kind of optimize the system around it to get it to, to go, but definitely not, not the easiest project I was a part of it.
Natalie Kuldell (02:16):
No, very, very tough. So, you’re not at Duke anymore though, right? You’ve left that area.
Stephen Payne (02:22):
Yeah. So graduated in 2013 and went back up to MIT. And I, I think we, we met up once when I was there with Ron Weiss’s lab. And one of the impetuses really was, I mean, I love the pattern formation project. It was cool, but practical applications, you kind of have to stretch a little bit. So I worked with Ron Weiss on RNA circuits to help differentiat STEM cells into beta cells. And the technology was pretty cool. Actually, I think a lot of the technology ended up getting spun out into a Strand Therapeutics. Not sure if you’re familiar with them, but yeah, they they’re doing mRNA. And I think they’re focusing on vaccines now, but
Natalie Kuldell (03:26):
Whoever heard of an mRNA vaccine?
Stephen Payne (03:31):
So my job was basically to get self-replicating RNA into IPS cells because direct genomic DNA modifications often get silenced in IPS cells. So I did some micro RNA switching. The idea was basically let’s, let’s switch on at the right time to give whatever factor to move to the next thing. I wasn’t there too long. I knew I wanted to get into industry and you know I definitely like Ron Weiss, and yeah.
Natalie Kuldell (04:14):
Oh yeah.. interesting project, learn a lot. And then when a nice opportunity to join industry comes along, I think, as a postdoc, that’s the right next step.
Stephen Payne (04:23):
Yeah, so yeah, I went to Greenlight Bio-sciences which they’ve done pretty well lately. I know they, they actually put a satellite site down here in Raleigh Durham but was part of an ARPA E project to basically start with methane and go to isobutanol. And it basically one of the, the advantages of the technology was it was all cell-free. So you could mix different extracts from different organisms. And so I, I did a lot of work with methanotrophs and a lot of work with E. coli to sort of the idea was let’s take methane, make it to methanol, make it to formaldehyde with methanotroph extract and with E. coli extract you can go all the way to isobutanol
Natalie Kuldell (05:22):
That’s so interesting. I haven’t, I’ve never really thought through that notion of sort of staging the extract so that the circuit would perform in series. Right. And that’s very cool.
Stephen Payne (05:35):
Yeah. It was really cool. It I definitely learned a lot and you know unfortunately you know, it didn’t really scale
Natalie Kuldell (05:47):
That’s the thing about extracts it, you know, biology is amazing cause its self replicates. And then when you start to go to extracts, you’re like, well, I’m taking away one of the really strong things about using biology.
Stephen Payne (05:59):
Yeah. Especially when you’re talking about a pathway that long, you know, so you know, actually we went to there was a conference that because they gave out, like it was ARPA E, they gave out like 30 of these grants to different academics and industry. And I think most people, the consensus was it wasn’t going to scale. So unfortunately they laid off our, our full team, but you know, that’s how it is. And so you know, applied to a lot of jobs from there. And all the jobs ended up being in San Francisco. So I was like, guess, I’m moving there. And you know, at this time it actually, the timing worked out pretty well because my, I got engaged. I got married right before then. My wife had just finished her PhD at Duke. So we were doing long distance for Boston to Duke for like, what was it a year or two? And you know, so that was a good thing. And you know, so she was looking for opportunities to, and so she, she got a job doing technical writing at Thermo Fisher in the Bay. And because she has a, she’s got a weird story too. She, she was, she got her journalism degree. Oh, that’s a nice looking guy.
Natalie Kuldell (07:29):
That’s Milkshake. We got her the year that I taught you, actually. So she’s an old lady at this point.
Stephen Payne (07:37):
Cool. And you know, then, then she read about the 1918 influenza virus and got went back to school and got a biology degree and then did her PhD in virology. So yeah, it’s
Natalie Kuldell (07:54):
So she’s kinda a busy now, too, right?
Stephen Payne (07:59):
Yeah. She was writing technical manuals for all the COVID testing that a Thermo Fisher was doing. And she was, she was quite busy
Natalie Kuldell (08:11):
What a story. And you have a child at this point.
Stephen Payne (08:19):
So yeah, I went to San Francisco, I took the job with REG Life Sciences. And I can’t say enough good things about the people I worked with there. They were just so friendly and it’s a laid back. I felt like maybe we were, we didn’t work as much, but we work more efficiently. We had just a great infrastructure in place because they were LS9 for, you know, they had a long time to figure it out. So I worked on, you know, a medium chain fatty acid that we are commercializing in Europe. We scaled it to 130,000 liter scale. So that, that was cool. Then I was kind of a team lead managing some research associates as well as you know, coordinating among metabolic engineering, high throughput screening, and fermentation to do an ExxonMobil partnership to make bio-diesel. The project was pretty cool because we were, I was a sugar utilization lead to sort of get alternative sugars used as well as glucose and at the same time. And we were doing
Speaker 3 (09:43):
Can just I just stop you there? You choose very hard projects.
Stephen Payne (09:50):
Well, yeah, that, that one I still say that one was probably easier than the other two, the Weiss project and the other one, but it was still, yeah, it was, it was good. So we, we I saw just the other day they, they published a patent on it. So that was good to see. And but you know a little disillusioned working for ExxonMobil, you know? So after I left they were acquired by Genomatica, and then I think later on when COVID hit ExxonMobil was like, you guys reached all your goals, but we’re not gonna do anything with it right now.
Natalie Kuldell (10:45):
Right we got, we got other fish to fry,
Stephen Payne (10:48):
So you know, I left and some of my colleagues said I was a little crazy, I guess I left there to start a company. And oh yeah, you mentioned my son. I need to bring my son, I think about six months before I did that, my son was born. So in March of 2018 and yeah, he’s the best little guy. He’s very sassy. He’s running around. He’s, he’s talking a lot. He just won’t like, we were waiting for him to talk, wait for him to talk. And then once he started talking, he just won’t stop.
Natalie Kuldell (11:30):
Yeah, here’s what I think.
Stephen Payne (11:35):
So he he’s been he’s been cool. He is around one year old. We, we moved back here. So yeah, I started the company to you know, I saw and this was even before a lot of the people were getting a lot of money for it, but I did see, you know, there were some people trying to make glucose to cannabinoids, and actually this might be where I got lazy, I guess I was like, why are you trying to do that whole pathway? It’s a very complicated pathway. So, you know, our, our idea was essentially let’s start with low value cannabinoids abundant ones and just do one or two step conversions. Right. So you know, I was doing a cell-free extract to, to do one of those conversions. But you know, it could also be applied to synthetic chemistry.
Stephen Payne (12:39):
So after six months in the Bay and realizing it’s extremely difficult to operate a company there without a lot of money. I moved down to Durham you know, since we were familiar with the area, but also, you know, there’s, there’s a lot of pharma here. There’s also a lot of ag tech and I thought the technology really went hand in hand with ag tech because you know there are certain cannabinoids we avoided where we knew the plant biologists are gonna, are going to totally kick the synthetic biologist.
Natalie Kuldell (13:26):
So let’s not do those. Let’s leave those for them. Yeah.
Stephen Payne (13:32):
Yeah, you know, I hooked up with my buddy that he was getting his PhD at Duke at the same time and organic chemistry and spent some time in pharma. And we developed a process to go CBD to CBN in a synthetic chemistry route. And it was really good process. We’ve scaled it to 10 kilograms per month. And you know, we, we were going pretty good on the revenue in terms of, you know because you could sell these at like 10 K per kilo. So that’s kind of what we’re up to there. We were looking at cell-free extracts to make you know, some of these conversions happen, but also using synthetic chemistry as well.
Natalie Kuldell (14:54):
So exciting. I, you know, when I hear all that you’ve done, it just strikes me that the ability to integrate so many different aspects of science, like we, we, so artificially segregate the way we teach and learn science and everything you have done has really integrated all, you know, they call it STEM, right. But all of the technologies, like the cell-free extracts and the engineering in order to like mix and match and optimize output, and then, you know, you’ve got the science, the math, you’ve got the mathematical modeling, you’ve got the chemistry, the biology, like you are like, you should just have STEM as a tattoo, bring it all together.
Stephen Payne (15:34):
It’s yeah, it’s exciting. I mean, you know, I, I know somebody once gave me the advice that I should there being a what do you call it expert in a very small specialization is a good thing to do. And I’ve, I’ve kind of completely ignored that advice. And I, I don’t know if that’s a good thing or a bad thing, but it certainly seems like, you know, looking around, you know, it seems like a lot of people are looking for people that can integrate this skills across things. I mean you know, if you pick the right specialty it’s great, but everything’s evolving so fast that and it’s too late now, so
Natalie Kuldell (16:25):
Well you have clearly made it work. And I think that that’s, that’s amazing. It’s a wonderful career trajectory. I, I, I think you’re doing amazing stuff. I’m sure it’s gonna go, you know off the charts, it’s going to be amazing. So that’s, that’s going to be really incredible to watch. I’m so excited for you.
Stephen Payne (16:44):
Yeah. I’m excited about what the, what the future has in store.