Episode 121 - Allison Squires: "If you're torn on a decision..."

Neubauer Family Assistant Professor of Molecular Engineering, Allison Squires, describes her experiment-filled childhood and all the joy science brought her. By walking through various opportunities, she found her place poking and perturbing molecules with her amazing team at the Squires Lab. Listen to her talk about how she got to her dream job and be prepared to feel her great enthusiasm for all the knowledge waiting to be discovered in the smallest particles in the world.

Transcript

Stephen 00:00
Hello, and welcome to The Course! I'm your host, Stephen, and today I'm speaking with Professor Allison Squires of the University of Chicago Pritzker School of Molecular Engineering. Professor Squires runs the Squires Lab, where she and her team poke, perturb, and otherwise manipulate tiny molecules in an effort to better understand them.

We'll talk about some of her earliest experiments, why she's so interested in perturbing these molecules, and how she became a University of Chicago professor. Professor Squires, welcome to the course. It's great to have you. How are you this morning? 

Allison Squires 00:34
Doing great, Stephen. Thank you so much for having me. Yeah, absolutely. It's a pleasure. 

Stephen 00:38
We have a lot to get to, but just to get the basics out of the way, can you tell us a little bit about your role and what you do at UChicago? 

Allison Squires 00:47
Absolutely. So I'm a Neubauer Family Assistant Professor in the Pritzker School of Molecular Engineering. So that means that I do interdisciplinary applied research, and I teach courses like Thermodynamics and Statistical Mechanics.

Stephen 01:01
Okay, and for listeners at home who can't see, there is a bunch of math on the blackboard, right? Professor Squires has sweet talk this morning. 

Allison Squires 01:09
That's from office hours last night, yes. 

Stephen 01:12
Well, thank you. We're going to get more into your current work, but right now, uh, we're going to go quite a ways back, and talk about when you were a kid, maybe, I don't know, like elementary, middle or early high school.

What did you imagine yourself doing with your career? 

Allison Squires 01:28
It's funny. My, um, my life aspiration, I think like a lot of kids, was to be an astronaut. And actually that was what I, I really thought I was going to do all the way up through high school and starting college. And I think once I really started taking science courses and talking to my professors, I realized that maybe astronaut is not the most statistically likely career. But I loved science and so that's how I ended up here. Yeah. 

Stephen 02:00
Maybe one of the least statistically likely careers. So what were you drawn to when you started taking science classes? Yeah like what route did you go down?

Allison Squires 02:11
Oh, gosh, I always loved science even when I was little, the science projects were always my thing favorite part of school. I loved everything. I loved reading, but you know, I was really lucky. I grew up in a very small town, but we had a great school system and we had teachers that gave us pretty open-ended projects.

Design a physics based musical instrument and then explain the physics of it or design a pendulum that will swing for the longest time or have the period closest to exactly one second. And these sort of open-ended engineering design projects that relate back to science teach you skills, teach you to design things, and that feeds pretty well into doing actual cutting edge research.

Maybe in a way you don't expect at first, you know, you think, oh, this is just a project for a science fair. But doing research feels so much like something that you could do as a hobby in your garage. You just have much better tools, a much better environment to do it in, that I do think that those sort of projects are exactly the right kind of preparation to do real cutting edge research later in life.

Stephen 03:19
I just have to ask, do you, do you remember what kind of instrument you made and how it worked? 

Allison Squires 03:24
Yes, I made sort of a glass harmonica, right? Out of spinning glasses with different amounts of water in them, they, it was all on like a geared board so that they would turn and you could play it with your fingers.

It was a lot, it was a lot of fun. It wasn't the most practical instrument. And gosh, the Physics of how the wine glasses vibrate and how all the different kind of complex tones right with primary notes behind them come out of this, I was not prepared to actually model that properly. But it was a it was a really fun project and I think it showed me the depth of all the things that I didn't know and what would be possible to explain if I could get access to the right modeling software and learn how to use it.

Stephen 04:07
Can you just sort of spell out for us your journey between like college and where you are now? Like what institutions have you attended and what did you do there? 

Allison Squires 04:15
I was an undergraduate at Princeton University, and I majored in mechanical and aerospace engineering, and I minored in physics and Chinese language.

From there, I got excited about the possibility of applying my engineering and physics skills to problems in biology, and in particular, problems at the nanoscale. So thinking about interactions of individual molecules, and how that influences what happens, let's say, in a cell or in disease. 

And I didn't know very much about biology, I'll admit, but I got accepted into a biomedical engineering program at Boston University and, I started working on these sensors, these devices called solid state nanopores, which are, they're actually conceptually pretty simple.

They're just a little nanoscale hole that you can pull DNA or proteins through and reading out the electrical current of salt that's passing through that hole that maybe gets blocked by a molecule lets you understand something about the molecule's properties, maybe the DNA's sequence or where the protein has bound to another molecule.

After my PhD, I went and took a postdoc position at Stanford University in the chemistry department, thinking about now how do we control single molecules, how do we control their behavior, and how do we extract maximum information about what they're doing, since, of course, you can't actually see a nanoscale object in the way that we see normal objects.

Stephen 05:41
So what drew you specifically to biomedical engineering? 

Allison Squires 05:44
Well, you know, it's funny. The research that I did as an undergraduate all related to finding Earth like planets. So I was part of a project that was NASA-funded called the Terrestrial Planet Finder Project, TPFC. And my role in that project was to try and figure out how to do speckle nulling, how to correct the images that you would create from this instrument that the team was designing that was supposed to fly on a satellite, to be able to look at distant stars and see the evidence that planets that were like Earth were orbiting around them.

And so, the correcting the images is an important part of this, but of course at the time I was just learning, I didn't really know what I was doing. But in order to correct these images, I was using what's called a MEMS device. So these are micro electromechanical systems, MEMS, and this is a deformable mirror, or this particular device was a deformable mirror that you could use to just correct the wavefront to get a much cleaner image.

So I had a taste of what Micro-world was like and what these engineered devices could do in an optical setup. I'd heard from friends that there were lots of applications for micro and nanotechnologies and optical systems in biology and in medicine. And I'd never tried that before, and I thought it sounded interesting.

So I thought, hey, why not? I'll try that. And again, a little bit of this is just, just random luck. I caught on to something that I thought, well, gosh, I think I'd like to try that. I haven't taken a biology class since high school, but why not? And it turned out great. I loved it. I, gosh, I probably embarrassed myself a lot in my first couple of years of grad school classes because I was taking the grad school molecular biology class.

And I'd never taken molecular biology. I'd taken AP biology in high school, so I knew about RNA, DNA, proteins, all this. But thinking about and really, and really understanding that we don't know so many mechanistic details of how biology works. We know that proteins fold and we know the patterns with which they fold, but we don't totally understand how they explore an energy landscape to fold efficiently and correctly.

We really don't know how these nanoscale details work. So, I pestered my professors with all sorts of questions about this kind of thing. And I think it really reinforced my decision to just give biology a try because it turned out there were all kinds of mysteries there that were, that needed new technological solutions, new ways to get information out of proteins and DNA. And actually that's what my lab does today. 

Stephen 08:30
Who were a few of the people who, who helped you along the way, who you, you know, credit with helping you get to where you are? 

Allison Squires 08:37
Wow. Lots of people for sure. So obviously this starts with family. My parents are, I mean, they're the world's best parents, they're both scientists.

My mom's a chemical engineer. My dad is a physicist turned computer science scientist. My mom went to business school after her undergrad and my dad got his master's. So they didn't get PhDs, but we were always a science family growing up. My sisters are now also, they're both scientists. One's a chemical engineer. One's a computer scientist. So apples don't fall far from the tree, I guess.

But they were just, they were just such fantastic parents. They always encouraged us to explore things and try things and experiment at home and read and, you know, they taught, my dad taught us math on napkins or at the dinner table.

And then I got to AP calculus and I was like, oh, this is, I actually already know some of this stuff, ‘cause I didn't realize that was what I was being taught. So having such fantastic parents was absolutely critical for learning and being exposed to new ideas at an early age and also being encouraged and feeling like I could pursue anything I wanted, even if it was kind of crazy. Research, trying to find things that nobody has discovered yet, or, or make a device that nobody had thought of before.

 Also, teachers along the way, from grade school teachers, I had a third grade teacher who I just adored, who would give us really hard math problems for third graders, and, you know, really made us, like, showed us that we could do them. Mr. Mill, he was amazing. 

I had teachers in high school, my physics and chemistry teachers, Mr. Grubbins, Mr. Fortiani, and English teachers too, and, you know, all sorts of things, but specifically chemistry and physics, my high school chemistry and physics teachers really made me want to go into science.

Our AP Physics curriculum was awesome, especially for such a small school. And it was all because of Mr. Gribbins. And we didn't have AP Physics, but my honors physics teacher said, you know what? You should just study for the exam. I'll help you. You can do it. This is fine. And so I did, and he helped me. And he, you know, he said, You know, we've never learned E and M, and you're going to have to do that on the exam.

But all you need to know is, It's completely analogous to mechanics, except that you add something called the right hand rule, and he showed me what that was, and he showed me how all the variables connect, and that's how I approached the exam, and it worked out great. So, yeah, grade school and high school teachers also, they're just amazing, honestly. And they're the folks who can spark your interest in something and give you the confidence to actually go after it once you get to college. 

And in college, everybody has that research advisor, or that one professor whose class is super inspiring. I got to work with Professors Kasdan and Littman in the Mechanical and Aerospace Engineering Department. They were the leads on this terrestrial planet finder project.

And they were just unbelievable. Professor Littman was part of developing the original dye lasers. Professor Kasdin, was an expert on developing optical systems to fly on satellites. Yeah. So they were both super inspiring and encouraging. And again, yeah, wouldn't it be here if I hadn't happened to run into those folks?

And actually, I should say, too, that it doesn't stop in college. It's absolutely critical that you, if you go and do a PhD or a master's, you need to find a research advisor who really believes in you and who you click with and where you think that their science is really exciting and you want to build on it.

And I was lucky to have that. My advisor was Professor Amit Meller. He's now at the Technion in Israel. He was absolutely amazing. He let me come in and pick any project I wanted to work on. And when the first one didn't work, he helped me figure out what would work instead. 

And my postdoctoral advisor, Professor W. E. Moerner is also amazing. He's gathered such an amazing group of scientists and he gives them the guidance and also the flexibility to pursue any project hat really inspires them and find the exciting, the exciting new science. So, yeah, kind of all along the way. 

And, you know what? As a professor now, like, I have mentors here at UChicago. Professors who's, you know, some senior professor. If I have a question, if I don't know how to do something, if we are having a technical problem with our project, I go talk to my colleagues. So, having those really inspiring mentors. Mentors to guide you along the way definitely doesn't stop at grade school or high school or even college.

Stephen 13:20
That's a good point. Yeah What is exciting you at the moment? Like can you tell us a little bit about your current research and like questions that you're thinking about at the moment? 

Allison Squires 13:30
My research group is has sort of two main sides to it as an engineering group. One side is trying to think about, maximizing the information that we can extract from nanoscale systems and specifically from single molecule systems, like single molecules interacting.

And we're particularly interested in the tricky problems of room temperature systems, right? Because for physics, if you want to know what's going on with one molecule, you just get it to hold still. You cool it down, or maybe you use something like an AFM or, or near field microscopy, and you can get atomistic precision if you're cold or in a crystal or something like that. 

But biology is messy and all the interesting stuff in biology happens at room temperature. Everything stops if you freeze it, right? So getting information from systems that are tiny and moving and messy is hard. And so there's lots of exciting science to do there. 

On the other side of the lab, we're thinking about how to do actuation in those systems. How do you perturb something? So to do a science experiment, right? You have to have this cycle of measurement, analysis, and then developing a new hypothesis so that you can go back and perturb the system. And our ability to I mean poke nanoscale objects to move a single molecule to go where you want it to and to interact with a particular other molecule. That's so hard, right? 

Something like an AFM cantilever, maybe you can like pick up a molecule and move it. But most of the ways that we have to do this require like a big arm or a needle, right? And we want to be able to do it remotely. So we're working with systems that can trap a single molecule and move it around and we can make really high precision measurements while we're moving it around.

Stephen 15:21
That's kind of mind blowing, honestly, for somebody, who’s not familiar with all of these instruments. Can you just tell us, I mean, you run a lab at UChicago, correct? So yeah, can you tell me a little bit about what it's like to do that? I mean, like what, what it actually entails to be the person in charge of this lab and kind of what the day to day, if there is a day to day experience, what that's like?

Allison Squires 15:46
Yeah, absolutely. So as a professor in engineering, I teach classes, but a huge amount of my time goes to doing research with my research team. And my research group has, we have eight graduate students, a postdoc, a research tech, and four wonderful undergraduate students. And so, my particular research group is very interdisciplinary.

We have a couple of engineers, we have a chemist, we have some biophysicists, we have some physicists, and everybody is working together. on different projects. Everyone has at least one project that they are in charge of. Um, the younger students are sort of learning to lead their project and the older students might be juggling even more than one project. And they're also part of a team on a project that somebody else is leading. 

And those projects might be, skewed more towards instrumentation development. So figuring out new techniques, new ways to extract information or manipulate single molecules or there might be applications of those devices. So for example, the sorts of information we collect are perfect for looking at photosynthetic systems where there's a naturally occurring, beautiful structure that has lots of pigments in it that collect light from the sun, collect energy and move that energy around very efficiently to the reaction center, where charges split to store energy inside a cell. 

And, traditionally, we think of these structures as being dynamic, because we have great detailed, detailed structures for them from the, like the X ray crystallographers, for example, or the cryo-em folks. And, what we're discovering, and many other people are, are looking at this as well, is that these aren't just static scaffolds. They move, and when they move, the paths that energy takes through them change. 

And our hypothesis is that some of these changes act like switches and fuses in photosynthesis. We're also looking at protein condensates and actin networks, basically the ability to look at, or poke, single molecules is useful for all sorts of aspects of biology and biomedicine.

Stephen 18:07
I love hearing phrases like poke and perturb used in a scientific context. 

Allison Squires 18:12
Well, that's really what it is, right? I mean, it's kind of crazy. Molecules are nine orders of magnitude smaller than we are, and we do not have, our hands are, we, we cannot interact with that. Our bodies are not calibrated to interact with that, and so we have to develop technologies that can interact with that effectively.

Stephen 18:34
I mean, if I'm hearing you correctly, there are these amazing, intricate, just really incredible systems in nature that we are, that we still don't fully understand, right. I mean, you're kind of exploring here just on a really, really small level. 

Allison Squires 18:50
Absolutely. It is astonishing that any life exists at all anywhere because the biology is so complicated and I should qualify this by saying I am not a biologist, but I have a lot of friends who are biologists, and I love talking to them about the systems that they are expert in. 

And I love that when you get even just a couple questions deep about the molecular details of what's going on, it's all just guesswork, right? They've done, biologists are great at designing very complicated, logical experiments, where they can infer and test hypotheses about what they think might be going on at the nanoscale, and the sorts of devices we develop allow you to actually see that. 

So it's really fun to talk to my biologist friends who say, Hey, I have this system. We think that there's maybe these molecules participating and that they might come together in this way, but we're not sure. And we say, Oh, well, we can just, we can just see that. Let's throw them in our instrument and we'll just look. Oh yeah, there are seven of that molecule and two of that molecule and oh, hey, what's that?

So that's, it's a really fun way to do science. 

Stephen 20:04
That's very cool. Zooming a little bit back out to our order of magnitude, what would you say that you enjoy the most about what you're currently doing? And if it's something we've already covered, that's fine. But yeah, what would you say you enjoy the most about this?

Allison Squires 20:18
The best part of the job is getting to work in the lab with my students. And of course, you know, there are lots of other things we have to do too, and so I don't get to do as much of it as I'd like. But I love going in and working with my students when they're taking data and tweaking the microscope, realigning things, designing a new build.

That's the best part of this job. And then of course, wrapping it all up, having the project be done, and getting to write it up and send it to send it to a journal to get published. 

Stephen 20:48
We're also asking people to, to please be honest and tell us what's something you don't really enjoy about this job.

Allison Squires 20:55
Oh my gosh, that's so easy. The email. I used to think, I used to think that professors were maybe all just a little flaky and so they might not respond to email right away, or they might miss an email because they were flaky? No, no. It turns out that we just get a lot of email. So if you email a professor and you don't get a response. It's not you. It's because they got 400 emails that day and they didn't have time to get through them all. 

Stephen 21:24
Is there anything specific or even just sort of like general pathways that you would like to explore in the future or like, you know, potential future projects or subject areas that you're curious about?

Allison Squires 21:37
Yeah, so one of the big blue sky frontiers that my lab is starting to think about, along with a lot of other labs here at UChicago in this big consortium, is the interface between quantum sensors, and biology and medicine. So, Chicago, UChicago in particular, has fantastic expertise in the quantum realm, quantum science and engineering.

And that means that I have colleagues who are developing, new, new devices, new sensors, that are exquisitely sensitive to electric magnetic fields, to ions moving around, basically to any changes in the local environment. And when you're thinking about things like quantum computing, having a quantum object be sensitive to its environment can be a problem, right? Because that causes decoherence, basically. So you don't want that for quantum computing or communications. 

But for sensing, these bugs become features. If you want to, for example, know how ions are moving through an ion channel, there's evidence that quantum sensors might have an advantage and be able to do it with more precision.

So, that is to say, The field of quantum science believes that there are lots of opportunities for using quantum devices as sensors for medicine and for biology. And in order to do that, you have to bring together two fields that normally do not talk to one another. If you ask your biologist friends about quantum sensing, they'll say, Yeah, no, don't know anything about that.

And if you show a, I don't know, a pipette or a cell line to a quantum scientist, they will run the other direction. So a lot of the challenge is getting these people in the same room so that they speak the same language and figuring out what challenges there are in biology and medicine that take advantage of the unique properties of quantum sensors.

So we have an NSF-funded Quantum Leap Challenge Institute, a center that is focused on this exact problem that brings together scientists spanning fundamental quantum theorists, all the way to physicians who are in the UChicago hospital. 

Stephen 23:55
Wow. Okay. That, yeah, seriously interdisciplinary.

Allison Squires 23:57
Very interdisciplinary. 

Stephen 23:59
It's very cool. What advice would you give to someone who's considering, you know, maybe going into your field or similar fields, or even just kind of generally like, interested in, you know, working in a lab. What advice would you give somebody like that? 

Allison Squires 24:15
The piece of advice that I've found myself giving to multiple people recently who were trying to make decisions about, what research group should I join this summer or where should I go to grad school or what should I do after my postdoc is actually all the same and it relates to, I remember being stressed about making these sorts of decisions myself when I was, well, even it starts when you're thinking about where to go to college, right?

I think at every stage, you feel like making a decision about picking a major, picking a research lab, picking a graduate school. You feel like each one of these decisions is critical, and if you make the wrong decision, it'll ruin your career or something. But at this point, looking back on the decisions I've made and sort of the random walk I've taken through different labs that got me to where I am today, I do truly think that if you're torn on a decision, then probably both or all the choices are good. And you will have many other opportunities to make decisions about what kind of research you do. 

So if you think you want to be a research scientist, you don't have to make the exact right decision at the beginning about what your major is or what research lab you start with. You just have to try something and learn something and then the next decision you try something new and learn something new and all those things together will lead you to what you, you know, maybe what you research eventually and maybe there is a path not taken.

I don't know. I love computer science and maybe I would have been a great computer scientist, but this path has worked out great and I do see that for my colleagues as well. You know, they think, oh yeah, I could have been a biologist, right? I could have done cancer immunology.

This is the thing that I see a lot of young people struggling with, and I remember struggling with myself, and I know it doesn't, it doesn't take away the weight of making the decision, but in retrospect, if you think two choices are pretty equal and you're torn between them, then it's okay to go with either one.

And it's important, once you've picked one, not to regret not doing the other one, because there's so much luck involved with research projects working or not, or getting along with an advisor or not, and you can't control any of those things when you're making the choice. 

Stephen 26:40
Yeah, that's really good to hear. Yeah. I think I probably have a good sense of it already, but just to put it to you directly, what would you say you really find fulfilling about what you do? 

Allison Squires 26:50
Honestly, it's kind of a dream job. Okay, there are administrative parts that can be a little annoying, but getting to work with students and mentor them and, you know, just be so proud of their accomplishments through their research projects.

Getting to, I mean, it almost feels like expanding my brain by having this team of people who are also excited to work on all the projects that I want to do. And I, you know, I sort of need to multiplex my capability to be able to, to do these research projects. Getting to teach, having amazing colleagues and being at the University of Chicago.

It's, it's pretty awesome. It's really fun.

Stephen 27:33
Thank you, Professor Alison Squires, for your time today. Course takers, if you enjoyed today's interview, please check out the other ones. Leave us a comment, subscribe, follow, and share this episode with your friends and family. You can find out more about the University of Chicago through uchicago.edu, or the university's campus in Hong Kong through uchicago.hk. Stay tuned for more, and thanks for listening.