Transcript:
00:01 [Natalie Kuldell – NK] All right, hi Shannon nice to see you!
00:06 [Shannon Johnson – SJ] Hi. Nice to see you too!
00:08 [NK] Thank you so much for coming to these office hours for the Idea Accelerator. It’s a really nice chance for the people who are participating to hear, you know, the point of view and the experiences of practicing bioengineers, and you are a wonderful example of that. So maybe you can introduce yourself. Just give your name and where you’re doing your work, and then we’ll go from there.
00:33 [SJ] Yeah, so I’m a fourth year PhD student in the Media Arts and Science Program – so that’s within the Media Lab at MIT. And the Media Lab does all kinds of things, and sometimes people don’t necessarily think of biology as one of those. But I’m in the Boyden Lab, or it’s also known as the Synthetic Neurobiology Group, and the focus there is creating technology to better understand the brain. And so there’s a variety of techniques and tools being made using chemistry or, you know, engineering of new microscopes – but my work is more in the realm of proteins and making molecular tools. So I will design a gene to then be expressed inside of neurons or other brain cell types, and then often that’s being used in conjunction with something like a microscope. So lots of my tools will fluoresce a color, and we capture that under the microscope, and later can do a bunch of analysis and other steps to understand the data that we’re getting from either cells or slices of tissue and, even in some cases, from animals that are awake that are doing some sort of behavior.
01:57 [NK] There is so much of what you just said that is probably like exploding people’s brains! Right like just going like wait what! So you’re exactly right: I don’t think people think about the Media Lab if they know something about it and immediately put it together with biology. I think the idea of neuroengineering is just so incredible like, you know, it’s so forward-looking and just it has always sort of felt out of reach. So, you know, to hear from you that there are all these, you know, tools and techniques that not only are happening, but they’re also coming together to do things that are possible in cells and in tissues slices, and also in live animals, I mean it’s really incredible. So I know you as a, you know, protein engineer – is I guess if somebody were to ask me what I know about you. I would certainly say that you’re one of the best protein engineers that I could identify. So do you want to say just a word or two about the work that you’re doing?
03:08 [SJ] Yeah, so one of the struggles just in biology in general when it comes to recording signals from cells to visualize things that are happening, is that we often rely on fluorescence. And fluorescence doesn’t work quite the way we wish it would. So there were certain proteins found in jellyfish decades ago that fluoresce when you use a certain wavelength of light to excite them, which is great and people have since then made lots of colors, you know, a whole rainbow of fluorescent proteins, but you’re limited in how many different colors you can use at the same time because each of these proteins – if you looked at like all the wavelengths you’re not going to have one single band, it’s not like just 480 nanometers is what’s being emitted, it’s more like a mountain. And so you can imagine the mountains start to overlap if you have too many of these different colors being expressed. So you’re really limited to seeing just four things simultaneously, so I could use green, yellow, red, and infrared at the same time or something like that.
So what I worked on was a way to bypass this, so instead of identifying a signal by color with the molecular tool, I co-invented – we identify signals by a location. So, you know, we have certain protein sequences that make small molecules that will self-assemble – kind of like legos – they’ll click into each other, and they’ll create certain shapes – three-dimensional geometric shapes – and so, you know, we combine genetically encoded sensors, so something that will flash the light in response to calcium or some molecule, when we connect that to one of the subunits, like a lego piece, that will assemble into one location – well it’ll assemble it several points randomly throughout the cell, but it’ll still be clustered together, and so we call this signaling reporter islands, because it’s like an island of one little kind of sensor signaling out. And we can then use sensors all of the same color, and as long as they’re not overlapping, each of these islands is going to give us some unique piece of information that we figure out the identity of that signal afterwards. So we can fix the cells and do antibody staining, which is a really old technique, but, you know, being able to identify after we’ve done the experiment helps us look at many more things because antibody staining is such a robust and old technique, there’s ways of doing many rounds of it and that gets past having that the being stuck with just four colors. If I could do four colors, strip that away, use the same four colors but now I’m identifying different locations and you do that over and over you can identify dozens of things because you can do rounds of staining. Whereas in the living creature you couldn’t really turn off and turn on and insert new things in the middle of your experiment like you can once the tissue is fixed and you know you washed chemicals in and out.
06:43 [NK] Yeah, it’s amazing it’s such a novel and creative approach to what has really been a challenge right these overlapping wavelength signals from the fluorescence, right you can’t tell blue from green right if the two curves are overlapping always. So to be able to find you know a really creative invention – and I love that you use that word invention because it really is inventive, it brings, you know, all that creativity and innovation to bear on a biological problem and a real challenge – and to build tools that makes you an engineer!
07:27 [SJ] Yeah and, you know, the really hard questions that we have often need new tools. So when my advisor Professor Boyden went into the job market people didn’t really think you needed neurotechnology, but now people understand. Like yes give me more tools; I need something new to get this data or to understand the data that we already have.
07:54 [NK] Right, right, It’s wonderful. It’s really great. Yeah, Ed Boyden is just a rock star – a very forward-looking individual and very creative and it’s so great that you’re in his lab. So tell me maybe how did you choose that lab? Was it something about the day-to-day in that lab that you liked? Or the challenges that they were facing or you know trying to address?
08:24 [SJ] So after undergrad I was working, and I hadn’t really thought about going back for grad school. So I’m not a fan of writing grants for those kinds of things, but I ended up getting involved with a different group: The Center for Bits and Atoms, which kind of shares the same building as the Media Lab, and that actually was my first time working with E. coli when I was working over there. And my boss – my mentor, my friend – there was the one who saw how much I was enjoying what I was doing, and said “why don’t you apply to do a PhD and continue doing what you love, but get a degree out of it.” And so it made sense that even though I can definitely go talk to people and find a way of collaborating or working on my own time with people with a bachelor’s degree, it really is a bit more constrained than than getting a PhD, where the expectation is that you’ve been trained to be more of a leader. Even though you can definitely be a leader with just a bachelor’s, but just as time has gone by, you know, more and more folks want more degrees to do certain things. So it made sense to do the PhD, and then more doors would be easier to get into than before. And so looking at the Media Lab – which groups were there – there are some in biology – it’s not the majority of groups but of those, there are really only two that do neuroscience, and I’ve always wanted to do more neuroscience related work. And Ed’s group was – or Professor Boyden’s group was – the one that was most interesting to me because it wasn’t doing the basic research, it was enabling other people to do their research even better. And so I really like being able to have a wider spread impact because, you know, I can make one thing but then hundreds or thousands, hopefully, we’ll use that tool eventually.
10:39 [NK] Yes! That I think is, you know, I’m also a scientist, and the notion that engineers can make tools that so many people use and that there is such joy and satisfaction out of building tools that others use. I think it’s, for whatever reason, a very well kept secret that is something that engineers are at their heart, you know, tool makers and problem solvers want to see other people using the things that they invent. The other secret that I think – I don’t know why it’s a secret – you mentioned, feeling like with a bachelor’s degree you could get so far and that to get further you know a PhD would sort of speak to leadership and your ability to solve a problem that nobody’s ever addressed before or challenge that nobody’s ever solved before. You don’t pay for graduate school the same way you pay for bachelor’s degrees. Right so I think when people are thinking it—
11:41 [SJ] It depends on – well that’s a special thing about STEM right, put it out there. If you’re in the humanities or even the social sciences, I want to say you are paying to play in those scenarios right. But in STEM, you know, you’re an employee, kind of, like you do a lot of research, you’re in the lab, or on your computer – however you do research – for your field a lot and so you are paid to produce new material, new works whether it’s written or you know physical things.
12:15 [NK] Yes so another just great advantage of going into a STEM field if you do pursue a PhD, it is not a degree that you that most people pay for, by contrast most people have a stipend of some sort while they are a graduate student so and getting their PhD, so that’s a also a nice thing to know that I don’t know that everybody knows about. But now would you have considered yourself an engineer going into your PhD, or were you more on the science side?
12:48 [SJ] I still don’t quite resonate fully with “engineer,” even now with what I do. Like there’s definitely some design principles we use, and, you know, sometimes it’s like “protein designer” or “protein engineer,” but I’d be willing to go with just like a “protein tinkerer” myself, as like rigid in – I mean don’t get me wrong I’ll put in my controls for experiments and such, but growing up I’ve always have “engineer” as very as a very precise field. Partially because for physics and mechanical engineers, the rules are known: so you can be very precise like .0001, you know, they really take precision seriously. And in biology, it’s so much messier. You really have to sometimes just do things to figure out the rules to go back and then design something for it, and so I like that more. Playing and trying to collaborate with biology, you know, because you can’t always force it to do what you want. You have to figure out what it wants to do naturally. Yeah so I don’t engineer like part of the time, I feel like an engineer.
14:05 [NK] Yes. Well I love that notion of just being there to sort of play and figure out where the – I mean, we don’t actually have to call ourselves anything! We just have to tinker, as you said, and sometimes it feels like the scientific point of entry, and sometimes it’s the more engineering point of entry. But either way, you get a tool that is useful to many. So when you were an undergraduate, did you study something that might be in life science or the scientific sort of school or more in an engineering school?
14:41 [SJ] Yeah so I studied biochemistry and molecular biology. I was definitely doing more basic research with the stem cells from your marrow – the mesenchymal stem cells – so I was always interested in like regeneration, but when I was able to start doing more of this tool development, I realized: with tools you can make one thing and then move on make another thing. Like you perfect it a little bit, but you really want to get the tool out so other people can play with it and then they can change and improve it, whereas the basic science it seems like you get your niche and you stay there for life or for many decades and, I as much as I enjoyed doing some of the stem cell work I did as an undergrad, it was more satisfying to make something and then I had the opportunity to move on to another project with the stem cell basic research. I would have to get to the point of impact to get to like translational research, it feels like it’s a longer journey in biology, at least.
15:57 [NK] And quite uncertain right, like a lot of research, you know, it stays – I mean CRISPR is a great example: right like that that understanding of the the the molecular biology of that sort of phenomena was not – is not – new, per se, and yet, now it’s become this very powerful tool that people are deploying in different ways. So I think you’re exactly right. I think with science it can be a very long road and maybe a never ending one if it gets applied to something right.
16:29 [SJ] Yeah, but that’s what’s great about – with CRISPR, you know, similar things like with the BioBuilders, with iGEM, the more people and the more perspectives you bring to the table with these problems, the faster things can move. And with being fast, we also want to be careful and have conversations of the direction that we’re speeding towards. Is everyone okay with this? You know, what do we have to be concerned with? So there’s a group at Media Lab that does stuff with CRISPR and they’re more on working with communities and having conversations about ‘if we use CRISPR on your mosquito population, or on your, you know, your rodent population, what are your concerns?’ And they’re doing more research on that process on developing a process and then also, you know, what are the thoughts of people on using this out in the wild. Even if you did it on the island, it’s not going to stay on the island. If history has taught us anything, nature doesn’t stay in one place for very long.
17:36 [NK] Yes look at look at where we are right now, right. Definitely biology is a worldwide phenomenon that we’re all understanding. Yep, yep. I had asked about your undergraduate career, but I actually probably should have backed up a little bit further and just sort of asked a little bit about like where you’re from, and how you knew you wanted to do science. And then where you went to school and things like that, so can you just say a little bit about your background?
18:09 [SJ] Yeah, so I grew up in Arizona in a suburb of Phoenix. Phoenix is kind of like Boston in that it’s a sprawling city. So in the suburbs of Phoenix, I went to a public school there that had, you know, your honors and AP classes, so when it was I think sophomore year, when I had the honors biology, I was really excited when I saw the codon chart, so the translation of an amino acid from the three letters of the RNA. And so it looked like a puzzle, like a decoder ring that you would associate with a puzzle in, and at that time, also was when – I mean, earlier had been Dolly, the first cloned mammal. She was a sheep that was cloned, so it was after that, but at that time was more now stem cells and specifically like induced pluripotent stem cells, so taking your skin cell and turning it into a stem cell or taking, you know, a fat cell turning it into a stem cell, and so between seeing the stuff about stem cells on the news or on the internet and then the kind of decoder puzzle aspect of that codon chart, I was really excited for the untapped, unlock potential that, you know, every cell could become anything! It still has that information, it still has that potential in there, we just don’t understand yet all the steps and mechanisms involved. So that’s where again I was interested in regeneration and that sort of thing. So that’s why when I got to undergrad, I was trying to find a group that did things with stem cells to try and help unlock that potential. And so whether it’s reversing damage or learning how to prevent damage when it’s a chance to regenerate versus scar tissue, it was exciting to learn more about stem cells and just how cells really make decisions in their own fate.
20:22 [NK] Yes, yep it is. I mean in some ways as you’re describing your interest in getting into this field at all and thinking about how it really speaks to really the heart of synthetic biology. The notion that we have a coding language this puzzle that’s been solved of how you take these codons and translate them into amino acids, right, so there’s a language there, but then there’s also the potential of cells to be reprogrammed and do things that we want them to do: so this pluripotent stem cell example – I don’t think would traditionally be considered a synthetic biology approach because it was kind of a, you know, just hack at it until we get it to do what we wanted to do right so, although that’s a very legitimate way that people sometimes engineer things. But yeah, it’s really interesting to think of that as sort of an early example of synthetic biology, or something that might have sort of whispered to the future of synthetic biology as a field so very cool.
21:27 [SJ] Yeah, it was really that pre-step because it’s hard to build a car without knowing some of the physics and mechanics behind it beforehand. So now that they know a lot of these you know cocktails that they can give to the cells people can take not just going toward the stem cell but now it’s: okay I have a skin cell, I make it a stem cell, then I make it a neuron, right. So now they’re going in every which direction that they need and trying to make a whole organ, so trying to get things to be many different kinds of cells interacting in the correct manner. So now it has the understanding the field has that understanding to do the synthetic biology approach now.
22:15 [NK] Right man I could just geek out with you for a very long time about it all! I think it’s just so really really interesting. I do want to sort of pivot just a little bit and ask you about your interest in education, because although we have lots of scientific things that we both find interesting it was actually your interest in teaching and education that brought our sort of spheres together. So is there something about teaching and education that you wanna speak to? Or why it’s important to you, or what you’ve done with it, or how you knew you wanted to do some of it?
22:53 [SJ] Yeah so it’s not something that I necessarily knew I wanted to do during undergrad. So weirdly enough, I think in like the third grade, I did write down I wanted to be a teacher when I grow up and then I shifted away from that and it was more science. But in looking back, I’ve always enjoyed learning: whether it was in school or going to a museum or trying to do some activity out of a book or with Bill Nye the Science Guy T.V. show. But as I got older and especially after undergrad and working and seeing not everyone, even when I was a student my peers they didn’t always enjoy learning or they they didn’t always see the other possibilities of it – that it wasn’t just you know do those standardized tests right, and that kind of that made me sad that not everyone could be as excited about learning, you know, not necessarily formal education but just learning. So that’s where in going the Media Lab where it’s interdisciplinary or anti-disciplinary, I don’t know what that other word necessarily means, but that was an example to me of like okay here’s maybe I can learn something from this institution about a way of blurring those lines between all the disciplines, you know, you don’t just learn math in math class, learn math through doing art, or learn history by doing a dramatization in a theater class of history. So I really want education to connect more easily to the real world. I work with folks who have a computer science background or physics, and it takes that diverse understanding and backgrounds to do the kinds of things we do – to make these tools. But that’s not apparent in K-12, you know, that you’re going to need to combine these different things to solve real world problems because they’re that hard, they’re that tricky that you can’t just memorize one thing and hope that will be – the solution will be just in that one area.
25:15 [NK] Right, right. I think, man, you are totally singing my song there. I very much agree. I think that not only is it essential that we consider the integration of all of these ideas into a solution or an answer or the way we work and think boy, also it’s really fun like it’s really like the best part to stay curious and to be learning all these unusual things and it’s so satisfying to put them together in different ways, right. To bring your personal self to the learning, that is what makes you an innovator and a scientist, engineer, you know, that answering questions on a test is good and important but it is not really what we do as scientists regularly every day, right.
26:10 [SJ] Yeah there is no answer book after a certain point – no answer key!
26:14 [NK] Right, right. You look around and you’re like “all right well I’m gonna have to figure this one out because nobody has the answer key to this question!” Yeah, so both daunting and also very satisfying and exciting. Right so well you are doing amazing work I think you are a wonderful teacher and a wonderful inventor and–
26:37 [SJ] Thank you.
26:78 [NK] Yeah, of course, I’m thrilled that you’re part of the BioBuilder community. I’ve always loved teaching with you and working with you on content and curriculum. I really also just really appreciate your taking the time today to talk and be included in this office hours. It does not look like we have additional people asking questions, so unless there’s some last words you want to add.
27:04 [SJ] Just try and take inspiration from anywhere as you’re doing – whether it’s the synthetic biology designs or in any other problem solving in life, really. There’s times when I take an art class because it’s fun, but I also learn how they’ve made their tools for their field and and often times in our group, we are taking tools or information from another field and applying it to neuroscience that no one in that other field was thinking that what they made was useful to neuroscience. So keep an open mind and keep your eyes peeled for the possibilities around you.
27:55 [NK] Yes, yes. I think I heard it at MIT ‘stolen with pride’ or ‘borrowed with pride,’ right. It’s not it’s not a knock on you if you take a tool from something else and apply it in a great way. That’s wonderful. That’s not something that you shouldn’t do; it’s something you should try to do. So that’s great advice. Shannon, it’s so good to see you always, so stay well, and good luck with all your work.
28:20 [SJ] Thanks and you too. Bye!