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Intro/Outro (00:01):
Welcome to Cryo-Talk a Bitesizebio Podcast, sponsored by Thermo Fisher Scientific featuring conversations between your host, Eva Amsen and experts in the field of Cryo-electron Microscopy.

Eva Amsen (00:15):
Today on Cryo-Talk we are joined by Liz Kellogg Assistant Professor in Molecular Biology and Genetics at Cornell University. We're talking about her research.

Liz Kellogg (00:24):
We are really interested, not just in understanding the mechanism of these CRISPR associate transposons, but in, um, adapting them as genome engineering tools,

Eva Amsen (00:33):
her advice for early career researchers,

Liz Kellogg (00:36):
you are the best judge of what is best for you. So have confidence in yourself.

Eva Amsen (00:44):
and what kind of music she listens to.

Liz Kellogg (00:46):
I listened to a lot of like two thousands pop because that was my time. You know,

Eva Amsen (00:51):
All in this episode of Cryo-Talk. Hi and welcome to Cryo-Talk. I'm Eva Amsen, and I'm here today with Liz Kellogg Assistant Professor in Molecular Biology and Genetics at Cornell University. Her research group uses Cryo EM to study molecular mechanisms related to DNA recombination and protein engineering. So Liz, how are you today?

Liz Kellogg (01:17):
I'm good. Thank you.

Eva Amsen (01:18):
Thanks for joining us. Now, we, we always ask our guests, um, to share a little bit of their research backstory, and I think you have a connection to one of our previous podcast guests podcast guests. Yeah. tell David. Yeah. Right. So I started my PhD. Um, I, I did my PhD of David Baker at the University of Washington and there I worked on, uh, protein structure, prediction techniques. So I did, um, a purely theoretical PhD. And then, um, I moved to Berkeley where I did a postdoc with Eva Nogales who was your previous guest and one of my favorite people. Um, there, I studied, uh, microtubule structure using cryo em, and that was around 2012 or 2013. That's about the time when the direct detectors came online. So I was very fortunate in the sense that I never had to collect data on CCDs or film. I went straight to the direct detectors and, um, of course we were astounded by everything that we could see at that time. We made a number of different discoveries regarding micro tubal structure, as well as the, um, the proteins that bind micro tubal and, um, affect their function. Things liket sot is a protein important in, uh, Alzheimer's. That is a factor in Alzheimer's disease. Um, and then, uh, actually to cap off my post-doctoral studies, I did started moving into studying recombinase and that has really led set me on the path for my research group here at Cornell.

(02:54):
Yeah. Cuz you now you're, you're looking at mechanisms that could be useful for genome engineering.

Liz Kellogg (03:00):
Can you tell me a bit about that? Yeah, so we're actually very interested in, um, things called transposons transposons are mobile genetic elements, they're selfish genes that, um, essentially replicate their own DNA. And so we were very interested in their ability to cut and paste DNA without introducing these, um, while bypassing double strand breaks. They essentially affect this, this process. They do this autonomously. Um, but the class of transposon we're extremely interested in now is called CRISPR associated transposons. And that means that these naturally associate with a CRISPR effector, these effectors do not cleave DNA they actually bind, um, the RNA and in a target DNA and they recruit the transposition machinery to that site for insertion of their genomic payload. And so a lot of people are very interested in using these, um, systems as tools for programmable DNA, insertion mm-hmm , um, it's very exciting and we're continually astounded by what we learn. Um, these transposons end up being very complicated, mechanistically speaking. And so, um, a big push in my lab is to uncover the molecular mechanisms utilized by these CRISPR associated transposons using Cryo EM.

Eva Amsen (04:19):
Yeah. So that, that, that actually leads me right into my next question is how are you using Cryo EM for that? .

Liz Kellogg (04:25):
yeah. Um, so Cryo EM is great as a, um, a tool as you well know, speaking to our previous guests because you don't need to crystallize your, uh, your, your target of interest. So we can actually reconstitute large ensembles of proteins onto DNA substrates. Now that the, you know, the challenge is to figure out what DNA substrate to use in order to stabilize the full assembly. But, um, we have found that Cryo EM is incredibly useful in terms of unraveling these mechanisms because we can visualize different states. Mm-hmm one of our previous papers, um, that was published in science in 2021 really was digging into the structure function relationship of a triple a plus regulator that was involved in, um, the programmable DNA insertion cycle of this transpose on. And so we characterized this protein in a number of different states and with its other transposition related factors in order to try to understand how this process was occurring. And that was not, that's not possible using any other technique really.

Eva Amsen (05:32):
Mm yeah. It's really, it it's one of those techniques that is it's, it makes you be able to look at things that you can't do in any other way, which is kind of what we've heard in, in every episode so far.

Liz Kellogg (05:46):
Yeah. We love it. .

Eva Amsen (05:48):
so if you, if you could look into the future of cry OEM, um, what do you think, where do you think it will be in like five to 10 years maybe thinking about the kind of applications that people are using it for?

Liz Kellogg (06:02):
Yeah. I think that's a really good question. I loved the previous episode with Eva Nogales mm-hmm I thought her answer was really great. Um, the, her answer was complexity and I would say yes, it com that's absolutely the right answer, but also, um, one thing that really excites me about Cryo EM is its ability. Like I said, to characterize protein structures that are not in the crystal state, so they're essentially doing whatever it is they do in solution you're flash freezing that. And then you're able to see that in an electron microscope. And I think, you know, that was something that we had dreamed of modeling back when I was in the Baker lab. That's very challenging. And, um, I, I think like the future of Cryo EM is in visualizing not just one stable ground structure, but you know, the transient states and the dynamics that are contained within that thermodynamic ensemble. And so that's what really excites me about Cryo EM and for the future. Mm-hmm I think that there's a lot of work that needs to be done before we get there, but that's what makes this so exciting.

Eva Amsen (07:11):
Mm-hmm yeah, definitely. Yeah. Um, and you started your lab in 2019, so it's not that long ago. How have those first few years been for you and, and what are you looking forward to doing in the next few years?

Liz Kellogg (07:25):
Yeah, I'm, that's a really great question as well. So we, so starting in 2019, I, of course, was affected by the pandemic, like every other assistant professor. Um, that's been exceedingly challenging and I think, you know, in 2020, when things shut down, it was hard because, you know, you, we had to keep our labs, our growing labs together. You had to maintain some sort of cohesiveness when everybody was alone at home by themselves. I think that was very challenging, but right now is still challenging as well for growing labs because of supply chain issues. Mm-hmm, , um, there is turmoil in the job markets. And so I think like, you know, that's something that's kind of that, that I reflect on. A lot of me and my, my peers is how, um, how do we help one another launch our labs? Mm-hmm while maintaining a, a great lab culture and doing cutting edge science. We talk about that a lot. And, um, furthermore, I would urge anyone who's listening, um, in the more senior positions it's like these, the pandemic is going to echo throughout the years. You know, it's not just this one year that, you know, we all got tenure block extensions for this is gonna continue on impacting all of the young assistant professors. And so I would really urge, um, more senior or more senior colleagues to keep that in mind when people come up for evaluation.

Eva Amsen (08:57):
Yeah. That's, that's definitely something to think about. And I guess also, yeah, working from home is not possible if you work in a lab. So , it's, uh, you'll, you'll have to, you're competing with them like PhD students, deciding whether they want to be in a lab or do something else. They, they see their friends going into places that get where they get to work from home and they might have to like, not do that.

Liz Kellogg (09:21):
Yeah. I mean, yeah. Also, you know, I mean, I don't have small children, but a lot of my colleagues with small, this is also the time when people start families. And I think that that was like, I don't have children, but I can't even imagine, you know, that must, that must have been so difficult. So, you know, that's even without the added additional challenges of having small children, so .

Eva Amsen (09:43):
Yeah. Um, so yeah. What, what, what are you, what are your plans for the next few years? Assuming no further pandemics .

Liz Kellogg (09:51):
gosh, I would love it if we, if we could have like, you know, returned back to the way things were, but I don't know that that's gonna happen anytime soon. um, so we are really interested, not just in understanding the mechanism of these CRISPR associate transposons, but in, um, adapting them as genome engineering tools. So I would really like to in the next, in the, in the next coming years to combine my training that I got from the baker lab in protein design, uh, protein modeling and design, as well as, um, my training in Cryo EM, so I would really like to meld those two. Um, we are really very quickly gaining, uh, very, uh, very good mechanistic understanding of how these elements work. And once we, you know, establish that foundation, I think then it turned, the question becomes, how do we adapt these tools mm-hmm for practical purposes. So we're, we're very interested in, in, um, going in that direction. That sounds exciting. There's some things I would love to do actually, you know, it's just not, not enough time to like, talk about all of 'em, but there's so many things and that that's one of 'em, but, um, yeah, I'll just stop there.

Eva Amsen (11:02):
and, and what about when you're not working? Do you have any hobbies?

Liz Kellogg (11:08):
So I used to have, um, I used to do ballet very seriously. Um, but it's been challenging to fit classes in mm-hmm . Um, while I'm trying to launch a lab, I also started horseback riding. That's one of the nice things about it because , you know, you get access to all sorts of, um, kind of country activities that you may not have access to otherwise . And I also, I also run now, so in order to kind keep, uh, to keep in shape because mental health is just as important as physical health. So I try to combine hobbies with exercise.

Eva Amsen (11:46):
Yeah. That's that's a good plan. yeah. Um, yeah. And you mentioned the countryside already, but that's, um, I think if we're going into our, our round of quickfire questions and that's actually my first question on the list is, do you prefer the city or the countryside?

Liz Kellogg (12:03):
I think they both have their merits. I like both. Um, I think I'm the kind of person that when I'm in the countryside, I, I like to be in the city and when I'm in a city, I like to be in the country. So , it's hard to say, I would say both are, are good and bad in their own ways. .

Liz Kellogg (12:20):
And do you like to cook? I love cooking. I love it. And I love to improvise. I love to just kind of go into my pantry and take out whatever I have and then make a delicious meal. .

Eva Amsen (12:31):
any, any favorite recipes you want to share?

Liz Kellogg (12:35):
My go-to is, um, salsa Verde Chilaquiles. I usually make that on, um, Saturdays, Saturday mornings .

Eva Amsen (12:45):
And, um, do you like reading? Do you have any book recommendations?

Liz Kellogg (12:49):
I, the last, well, I, I loved reading. I don't read as much as, um, I read a lot of papers. I don't read a lot of books, although I, I really would love to get back into it. The last book I read was bad blood, and this was the, um, book by John Carenou about the Thenos story. That's the last novel I read.

Eva Amsen (13:08):
So sounds interesting. I also kind of want to see the, the show about that. .

Liz Kellogg (13:14):
fascinating do it. .

Eva Amsen (13:18):
um, speaking of shows, um, are there any films or TV shows that you watched in the last year or two that you would recommend?

Liz Kellogg (13:27):
Hmm it's a really good question. And actually nothing really pops into my mind at the moment. Um, there's a movie that I've been wanting to see, which is Everything Everywhere All at Once.

Eva Amsen (13:42):
Oh yeah. I have a meaning to see that. I also still need to see it. Yeah. Maybe by the time this airs, we have both seen it, but.

Liz Kellogg (13:49):
I hope so. A really good one.

Eva Amsen (13:51):
Yeah. And do you listen to music.

Liz Kellogg (13:55):
all the time? Yeah.

Eva Amsen (13:57):
Like what do you listen to?

Liz Kellogg (13:59):
Um, I love pop music, so I listen to a lot of like two thousands pop because that was my time, you know, mm-hmm, a lot of Katie Perry, um, and let's see, uh, Nicki Minaj, stuff like that.

Eva Amsen (14:18):
So do you listen to music while working or just while you're running or all the time?

Liz Kellogg (14:23):
All the time. All the time. I, I listen to music and I listen to podcasts. Mm. And I listen to the Cryo-Talk podcast as well.

Eva Amsen (14:30):
Of course. yeah. And if you were not a scientist, what would you be?

Liz Kellogg (14:36):
Yeah, that's an interesting question because I actually, with my colleagues, we sometimes think about this, but, um, I think I would be a writer because I, I love, I actually love writing. Um, so I think, I don't know if I would seems like a big change, you know, writing scientific manuscripts to novels, but I have a couple ideas.

Eva Amsen (15:00):
Hmm. Well, you can do both as we we've learned from, um, from our first podcast guest Joachim Frank, so he's, he's managed to do both, so it's possible. .

Liz Kellogg (15:12):
but he's in so incredible. later after I win the noble prize. you gotta do that first and then yeah. .

Eva Amsen (15:24):
um, and something else that you mentioned earlier is, um, you also have a podcast. Do you maybe want to tell people about that?

Liz Kellogg (15:32):
Mm-hmm sure. Yeah. Thanks for giving me the opportunity. Um, so the podcast that I developed along with, uh, Michin Franco and Mimi Ho is called The Plunge. And, um, we actually interviewed, uh, six different members of the Cryo EM and community. And, um, we asked them things that, you know, we had Al always wondered things like, you know, your most significant discovery. How did you feel about that? Um, what is the future of Cryo EM? Ye as well as, you know, more practical things that we wonder about for ourselves, like how do you create a thriving lab culture? How do you mentor the next generation of students effectively? Um, things like that. So I had a lot of fun doing it. Um, I hope that it's people enjoy listening to it and watching it, so, but we'll see.

Eva Amsen (16:26):
Yeah. And now you get to be a guest here, so .

Liz Kellogg (16:29):
thank you so much. Yeah.

Eva Amsen (16:31):
Um, yeah. So I've got one more question for you. And, um, do you have any advice for researchers who are just starting out their career?

Liz Kellogg (16:42):
Yeah. Um, I also think about this a lot too. I mean, having advice, students, I think a lot about how best to guide them. Um, I kind of struggle with this because I feel like everybody's trajectory is so unique and what works well for me, someone like me may not work very well for someone else. Mm-hmm . Um, so I guess personally, what I found is that in my career, I would ask many people, all my mentors and, um, more senior colleagues for advice, and you get all sorts of different advice about what's best to do. And I think what I realize is that everybody's giving advice based on their own experiences, um, about the challenges that they encountered at the time that they were trainees or at they were at that particular stage. So what I always tell trainees is that it's good to seek advice and you should, um, but keep in mind that, you know, you are the best judge of what is best for you. So have confidence in yourself. Um, and ultimately you're the one who gets to decide, you know, so, you know, you can, you can get advice, but I think that, you know, have confidence in your own sense of direction about where to go next. Yeah.

Eva Amsen (18:06):
Yeah. That makes sense. Cuz everyone is different and.

Liz Kellogg (18:09):
I mean, you're the one that knows best about what you like, what you enjoy and where, you know, where you should go next, what you should do next, things like that. Right. So yeah.

Eva Amsen (18:19):
Yeah. It's I always personally find it hard when, when people like ask me for advice, because what do, do you want me to tell you what I did cuz I that's the only experience I have, but yeah, .

Liz Kellogg (18:32):
exactly. I have a very, very limited, you know.

Eva Amsen (18:35):
Yeah. I've done one thing. That brings us to the end of today's episode. Thanks everyone for listening to or watching Cryo-Talk.

Liz Kellogg (18:44):
Thank you so much for having me.

Intro/Outro (18:47):
Thank you for listening to Cryo-Talk a Bitesizebio podcast, sponsored by Thermo Fisher Scientific to view all audio and video recordings from this series, please visit bitesizebio.com/cryo-talk.