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Jennifer Lippincott-Schwartz (Howard Hughes Medical Institute)

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#1 — Join this informal chat between Peter O’Toole and Jennifer Lippincott-Schwartz of The Howard Hughes Medical Institute. Beyond kayaking to work and a passion for plants, Jennifer explains how she became interested in Biology from her time teaching in Africa, and how she was fortunate enough in her early career to work alongside some of the true giants of cell biology.

Very few cell biologists have had so many major impacts on the field, and underpinning most of her work was the use of the microscope, with many discoveries going hand-in-hand with the development of microscopy itself.

Jennifer shares some great stories as to how these developments came about, what it is like to work in the Janelia Research Campus and how to Kayak to work (hint: don’t do it in the dark!).

Follow Peter O’Toole and the Lippincott-Schwartz Lab on Twitter!

 

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This is a machine generated transcript and may not be 100% accurate.

Intro/Outro (00:00:03):
Welcome to The Microscopists a Bitesize Bio podcast. Hosted by Peter O’Toole, sponsored by Zeiss Microscopy. Today on The Microscopists.

Peter O’Toole (00:00:18):
How’d you keep that drive and balance that pressure that you have.

Jennifer Lippincott-Schwartz (00:00:23):
Well, first off we don’t write grants, so that’s really nice. So you don’t have the pressure of constantly getting a feedback or worried about writing a grant. Basically we write papers, we write reviews, you do the science.

Peter O’Toole (00:00:39):
Welcome to The Microscopists. Today, I talk with Jennifer Lippincott-Schwartz of the Howard Hughes Medical Institute at the Janelia Research Campus. Very few cell biologists had so many major impacts on their field. And underpinning most of this work was a use of the microscope itself with many discoveries, go hand in hand with the development of microscopy. Beyond incredibly kayaking to work and a passion for plants, Jennifer explained how she became interested in biology from a time teaching in Africa and how she was fortunate enough in her early career to work alongside some of the true giants of cell biology. Hi, I’m Peter O’Toole, and today, The Microscopists, I’m going to be talking to Jennifer Lippincott-Schwartz of the Janelia Research Campus over in the US. Jennifer, hanks for joining us today.

Jennifer Lippincott-Schwartz (00:01:34):
Thank you, Peter.

Peter O’Toole (00:01:37):
Janelia Farm must be an awesome place to work. So yeah, I’ve been there. I’ve visited it inspired by it. I, you know, I was envious, but what is it actually like to really work there.

Jennifer Lippincott-Schwartz (00:01:50):
It’s pretty amazing. Every day that I walk into the campus, I feel like I’m walking into another sort of futuristic world. It’s the first time that I’ve ever thought about where you could really create a enclosed environment that you would feel perfectly happy living in forever, sort of I mean, there’s just so many windows that you feel like you’re in a spaceship actually. And and that gives you a really cool feeling about your research. That you’re, you’re sort of you’re in a special place. And so you must be doing things that are comparable to that. So it makes, it really impacts, I think the way a lot of people feel about what work they’re doing being in that beautiful environment,

Peter O’Toole (00:02:47):
How, how tough and competitive is it? These are the elite scientists, certainly from when I look from the outside, it is full of elite scientists.

Jennifer Lippincott-Schwartz (00:02:57):
That’s what’s so cool is you do not feel in any way that there’s that competitive aspect to the place. And that really surprised me because, you know, there’s a lot of other places that you go to and you just walk in and you’re just like, Oh my God, you know, this is a scary kind of place, but at Janelia you don’t feel that way at all. People are, because it’s small there, the labs are small, the PIs don’t have big empires. And as a consequence of that, they are willing to just talk to anybody. So you can, you know, you bump into anybody at the coffee place at the coffee shop and you can talk to them. So it’s, it’s, it’s really nice from that from that perspective, now I should say that I’m not a postdoc at Janelia and that’s different. I mean, I have to talk from a perspective of somebody who has come there as a senior scientist. But my sense is that the postdocs and the younger people also feel invigorated in the same way that I do.

Peter O’Toole (00:04:05):
What about the pressure though? Cause again, to maintain that, that, that the momentum that you carry into there to continue that momentum, how do you keep, what motivates you, how you keep that going?

Jennifer Lippincott-Schwartz (00:04:18):
You mean in my own lab or to, are you talking broadly about the Janelians’ themselves? How do they motivate themselves

Peter O’Toole (00:04:26):
Perspective? How do you keep that drive and to balance that pressure that you have?

Jennifer Lippincott-Schwartz (00:04:32):
Well, first off we don’t write grants, so that’s really nice. So you don’t have the pressure of constantly getting a feedback or worried about writing a grant. Basically we write papers, we write reviews, you do the science. And so it’s all about the science and actually there’s a lot of collaborative science going on at Janelia, which is really cool. And you bump into people and you start up all kinds of collaborations between, you know, between different labs and that’s, that itself is very motivating when you have a larger set of people that are sort of participating with each other to push things through. For me I try not to let exterior things like a grant or whatever be a motivating, worry, or concern. There’s enough things that you can get concerned about to sort of have that impact you. What I think is what I try to have motivate me is the science, the excitement of the science. Like I don’t like doing things that are not significant.

Jennifer Lippincott-Schwartz (00:05:55):
I mean, you know, I think it’s really there’s, I always tell my students, I mean, they’ll, they, they’re happily moving, you know, with their experiments and you know, they want to write a paper and if it’s not significant you know, my view is, look, it takes so much effort to get a paper out, to get a paper, to make it really, really good, that you might as well have it on something that is really changing our perspective of things. So in anything that we work on, we try to look at it from a perspective that gives a new, a new view, a new twist in some way. So, so, you know, that’s what gets me excited.

Peter O’Toole (00:06:49):
Yeah. So you’re not having to write grants. Then you have more freedom of how you can move the direction, you can move your research in.

Jennifer Lippincott-Schwartz (00:06:53):
Yeah.

Jennifer Lippincott-Schwartz (00:06:54):
Oh, wow. Yeah. I mean, I absolutely I mean, I think there is value in writing grants in that it forces you to conceptualize an issue in a very rigorous way, but it also narrows your thinking. And you know, there’s particular ways that you write grants in order for them to be successful, which limits the creativity that you can put into that grant. So by not having to write grants you, you can be super creative, but at the same time you can get out of control and that’s the other aspect. And that’s the other thing that I have to worry about with people in my lab is they have so much freedom that, and they, you know, once you are in a lab and doing experiments, it’s hard, you don’t want to stop doing experiments, but there’s a point where you got to say, look, we’ve got to, we’ve got to cap this thing. You know, it’s time to put this moving, you know, thing that we’re looking at into some kind of order that we can present it to the outside world.

Peter O’Toole (00:08:08):
I can imagine it can be quite difficult to lose focus, you know, to skip too early.

Jennifer Lippincott-Schwartz (00:08:14):
Yeah. So it’s two. So on the one hand, you know, the sort of traditional granting system forces you to be very narrow in the way that you’re doing your work. Not having that you know, brings its own challenges, which is, it’s very hard to focus. I mean, you’ve got to really you know, have your own sort of conceptualization of what’s what’s important. What’s not important for sort of moving science forward.

Peter O’Toole (00:08:50):
So I, I, my, my memories of Janelia Research Campus was very much the lab environment and the collegiality was fantastic. Yeah. The beer at the bar was also, there was a particular stout that was mind blowingly good. Rather strong though. So you wouldn’t want too much of it. But also Selden Island, and I used to get out, I used to run round Selden Island each morning. So I know. Yourself, do you run around Selden Island? I know you enjoy some running.

Jennifer Lippincott-Schwartz (00:09:18):
Yeah. I, Seldon Island is really an incredible place. It’s a, it’s a flood plain that Janelia owns because I mean it, when they bought the property basically it’s a huge six mile circumference Island that could not be developed. So they just bought it and it’s a personal sort of dream world for people to just walk or jog or bike around. And it’s like heaven. I mean, I just totally love it out there. There’s, you know, wild animals, you know, deer running all over the place. And I think everybody at Janelia has a some experience or another with that, with that Island.

Peter O’Toole (00:10:08):
So if I’m correct, tell us about this picture there. So this is a picture of a kayak with this beautiful tranquil water with trees either side. Tell me a bit about this.

Jennifer Lippincott-Schwartz (00:10:19):
Okay. So to the right of that, the trees to the right is Selden Island and that’s my kayak and it turns out so Selden Island borders, the Potomac River, which separates two States, Virginia and Maryland in the United States. And that’s the Mason Dixon line. I mean, basically that’s the difference between Maryland and Virginia is the difference between North and South USA. So it’s a, it’s an important river actually. The armies during the civil war were going back and forth across that river. But I live in Maryland and Janelia is in Virginia. So I have two choices for getting to work. I can either drive across the river downstream about 10 miles or so which involves heavy traffic and can be a total nightmare in terms of gridlock traffic, or I can kayak. And that’s what I’m doing, right there. So when it’s nice outside and you know, I feel up to it I will take my kayak and just paddle to work. And it’s really spectacular.

Peter O’Toole (00:11:42):
How often do you get to do that in a week?

Jennifer Lippincott-Schwartz (00:11:45):
Well, I’ll do it maybe two or most around two, two times a week during the summer when it’s nice. I’ve had some experience, you know, you can’t do it during the winter or the late full because otherwise you’re going to be going home at a very early hour because you do not, you don’t go to Selden Island when it’s dark. Cause it’s scary. I’ve been there and gotten sort of in a situation where I crossed the river and I realized I didn’t have my car keys or my cell phone or anything. And it was dark, it was pitch dark. And there was nothing on either side. On the Maryland side, it’s complete wilderness. So I realized I had to get, I had to go back to Janelia and basically stay over the night at Janelia, but it was dark. So I had to be kind of, you know, I was kind of in the pitch dark and then I had to get on that Island and it’s a four mile bike ride to get, you know, back to Janelia. So it was not, it was scary, you know, because there’s just all kinds of weird animals. And I mean, it sounds like I may be a wimp, but it’s always like

Peter O’Toole (00:13:02):
I was running round in my head torch so I was in January, February. So I had the head torch early, early morning before dawn started.

Jennifer Lippincott-Schwartz (00:13:09):
That’s what I should have had was a head torch. And I didn’t, so that was my mistake.

Peter O’Toole (00:13:16):
Sounds cool. So, you’re now at Janelia Research Campus? Where did you, why did you even start biology? What was your inspiration? I presume your first degree was biology.

Jennifer Lippincott-Schwartz (00:13:28):
Yup. Well actually, no, actually, so my first degree as an undergraduate was philosophy and psychology that was at a, a liberal arts college called Swarthmore College, a Quaker school in Pennsylvania. And I had gone in thinking that I was going to be a biology major because, and I took a lot of biology courses, but it, this school is really well known for its philosophy and sort of sort of broader perspective of human nature and humans. So I got really drawn into psychology and philosophy during that period and graduated in those fields. At that point, I really had no clue what I wanted to do when I finished graduation. And so that’s where things really got fun in life. Exciting my future husband and I, who he was a Swarthmore student as well. We decided to go out to Africa to Kenya and teach high school.

Jennifer Lippincott-Schwartz (00:14:42):
And so we got, cause basically we had never seen the world, you know, it’s like we’ve been at students our whole life. You know, we need to understand the world to get a better perspective of what we’re going to do for the rest of our lives. So we both this was in 1974/75. We went out to Africa to Kenya the Western province and taught high school. And this is where I got really transformed into science and biology because I realized first off psychology, the kind of psychology that I was doing, just seemed completely irrelevant to this environment and to these people. And I’m also, actually sort of a funny story, but I had been in touch with a professor at Cornell, before, as I went over, who was doing the psychology underlying mathematical thinking in children.

Jennifer Lippincott-Schwartz (00:15:47):
And he wanted me to do a survey there for mathematical thinking. And so at some, you know, after a couple months when we had gotten there, I went out in the field with some students to try to, you know, get some of the data that he wanted. And, and I quickly realized this is nuts. That these, the fact that he’s sitting in his ivory tower at his university and has no clue what these kids are experiencing and what these kids know versus don’t know in their particular environment really turned me off to the kind of study that was associated you know, with this field at that time. So that, you know, I quickly sort of cut ties with that and realized really dove into, you know, being a teacher at this high school and they had no teachers in any of the science classes.

Jennifer Lippincott-Schwartz (00:16:49):
So I taught physics, I taught chemistry and I taught health science. And it was, and it was a high school, it’s called Harambee School. It was student kids who girl, actually all girls who were living out in the bush. We were out in a I mean we were surrounded by mud huts everywhere and our, and our school had dirt floors, no electricity. You know, I basically had to write the lesson plan on a blackboard and it was really transformative. It made me realize you know, in order to really help this, you know, this community, these people we needed, cause they’re, you know, I could see all kinds of issues with the way that they’re you know, the way they’re growing their crops. The health conditions, the lack of knowledge of really basic fundamental things that could help their community live in a more comfortable way.

Jennifer Lippincott-Schwartz (00:18:00):
So it also transformed my husband because he decided to go to become an international go into international law. And so when we came back, we knew exactly what we wanted to do. And and on our way back, we did some really wild things like going to the Swat Valley, Pakistan and the Soviet Union and Afghanistan, different parts of Afghanistan. It was really fun. This was, you know, way, way early. I mean, like now, you know, the Swat Valley, you know, it’s like a place that you would go and get sh well, I mean, actually back then, it was pretty bad too. It was scary actually. It was some of these places were very scary. We also went into Uganda when Idi Amin was there and you know, searched for gorillas. And it was a very exciting time that sort of, in some ways it, it got me. So when I ended up back in the United States going to graduate school, I was ready. I mean, it wasn’t like, Oh, I want to experience the world. I knew what the world was and I knew what I wanted to do within it. So that, that made a huge difference. And that was a year a year, you know, a year of teaching there.

Peter O’Toole (00:19:31):
Yeah. And so that’s when you went into a degree in biology I presume?

Jennifer Lippincott-Schwartz (00:19:36):
Yeah, so then actually, it took me another two years before I actually got a degree in biology cause so my husband immediately went to law school at Stanford. And in order for us to survive financially, I decided to become a teacher. I was a high school teacher for another two years at a private school. And again, I was teaching physics, chemistry or science algebra and you know, it sort of drew drew me into the world of biology and physical sciences. And that, that was a really great experience too, because this was a totally different environment. It was all boys, a private school, the kids were riches all get out and I could compare, you know, being in a school with all girls, you know, who dug, you know, who were, you know, farmers and, you know, living off the land versus these, you know, Palo Alto, you know, elite group of boys, it was just incredible. So it was fun. I mean, it was very interesting to say the least.

Peter O’Toole (00:20:50):
So you were supporting your husband over that time, so you chose your career to support your husband. Actually, which is very similar to my wife actually. So we both could have done PhDs, both had the options and she went into teaching actually and supported me through my PhDs days. And I, it’s nice to see. Yeah. I think partners do do things as a team.

Jennifer Lippincott-Schwartz (00:21:10):
Oh yeah. No, absolutely. I mean, it’s, it’s very interesting because nowadays a lot of couples just feel like, okay, no problem. I’ll live in San Francisco and you’ll live in New York city. That for, for at least my relationship with my husband, that’s not something that we would want to do. I mean, we had spent so much, you know, we had gone through so much together, you know, as a team, you know, teaching in Africa, traveling around the world, that there was no way that we were not going to stay in the same place. So after he finished law school at Stanford we moved to the East coast where I started work in a PhD at Johns Hopkins. And he started at the State Department his career there in international law. So anyway, yeah,

Peter O’Toole (00:22:06):
That that’s quite a change and you can see how that’s morphed into your degree. And then I guess, into your PhD and into early postdoc in days. How easy did you find the transition? And did you find any major challenges at the time of getting there and doing your PhD or was that, that experience, the motivation that made it a lot easier to go through?

Jennifer Lippincott-Schwartz (00:22:32):
So before I started my PhD, I did a Masters. So what I did was my, the last year that my husband was a student at Stanford, I became a Master student at Stanford and started taking courses and and worked actually in a lab there. Phil Hanawalt who did DNA repair work, this was the period of Stanford’s unbelievable impact in molecular biology. This was the molecular biology revolution period, 78 to 80. And you know, Paul Berg, Arthur Kornberg, these greats were, you know, around that campus. And I, I had classes with them and I realized that I was in an environment with total scientific giants. It was just totally clear. And I mean, they, they were so excited, you know, the first time that you’ve replicated DNA in a test tube, you know, the first time that you’ve purified, you know, enzymes involved in DNA replication, and you could see this palpable excitement on that campus that you just could not, it couldn’t rub off on you.

Jennifer Lippincott-Schwartz (00:23:54):
So I felt that I had, and that was really formative experience for me because I took that. And in other environments you could sort of compare, you know, like I know what true giants are. I know, you know, so, you know, if you’re in another environment that you may feel sort of intimidated by the people you just say, well, how do they compare to Arthur Kornberg or Paul Berg, you know, and you realize, you know, they’re not, you know, they’re, they may be at some level that, but you’re not going to necessarily be intimidated by them. Because you’ve, you know, you’ve, you’ve got that grounding in a really an educator, you know, what really great education is, know what really great sciences by being around those people. And that is really important for anybody’s career is to be in an environment where you see people who are truly outstanding so that you can in some way, hope to be them, see them as a model for your own career. Now, at that point, I was not thinking that I would have any, there was no way that I wasn’t any way trying to compare myself to those people. It just like, but it’s so much fun to have, you know, it’s like, you’re, it’s so much fun to have idols. And so, you know, they were idols, it was cool

Peter O’Toole (00:25:30):
That, so that was the molecular biology explosion, seventies, eighties, I think you’re looking at the late nineties noughties. And even through now, I think microscopy has really driven a lot of fundamental research in many areas of biology.

Jennifer Lippincott-Schwartz (00:25:46):
So what’s so cool. Okay. So so when I left Stanford, that was the molecular biology sort of revolution and came to Hopkins. I landed in a lab Doug Fambrough, where he was working with monoclonal antibodies, which was another kind of revolution. You know, the Nobel prize for monoclonal antibodies was seen as a critical way that you could begin to identify proteins within cells with specific labels because you could tag a monoclonal antibody with a fluorescent probe. And so that was my entree into microscopy reattached, fluorescent probes to monoclonal antibodies that targeted different sub cellular structures. And the, my PhD project was basically I had a monoclonal antibody library that I was screening and my PhD advisor said, just pick whatever monoclonal antibody you want and purify, characterize the protein. And so I chose first off, I by screening it.

Jennifer Lippincott-Schwartz (00:26:57):
I saw all these different distributions of proteins within cells, and nobody could tell me what they were. I mean, it was like, what’s that, you know, like, what’s that, what’s that? And I realized, Oh my God, you know, this is like incredible, you know, we don’t understand how these proteins, what these organelles are. So I chose the monoclonal antibody that I focused in on recognized the major lysosomal membrane protein, lamp. And that’s what I characterized. So I, I spent a lot of time studying lysos, well, first off we had to show that this was a lysosome. And you know, the only definition of a lysosome at that point was from electromicroscopy and things that are taken up from the outside, get concentrated there, but to be able to come in with a monoclonal antibody and identify those organelles was just really exciting.

Jennifer Lippincott-Schwartz (00:27:58):
But what I think the key for me with microscopy is first off, you had to use microscopes to look at all of this. But secondly, I realized very quickly that this, the protein that I was looking at on that lysosome did not stay on the lysosome all the time. If I treated cells differently, if I lowered pH like with chloroquine it moved to the plasma membrane. So it made me start thinking that these proteins are actually migrating and that their intracellular pathways that are really defining the way that these proteins distribute within cells. And so that was the, the transition to my postdoc where you know, I was fully engaged in trying to understand organelle biology and intercellular trafficking pathways. But again, we were limited to inverted microscopes. It’s just, it’s really amazing when I tell my postdocs and students, they just can’t believe what life was like, you know, in the eighties, you know in terms of biology, cell biology,

Peter O’Toole (00:29:15):
But they’re going to be thinking, cool, you are so lucky because all these unknowns, now we know them so well, how do I fall forage a career now, when so much is known, but the technology has moved forward so much. We can now still, it’s still rich. I think there’s still so much in mind and discovered with the new technologies.

Jennifer Lippincott-Schwartz (00:29:35):
Unbelievable. And I think it’s very important if you what I realized, and basically I think this came out of being trained in philosophy, including in the history of science and the philosophy of science, you need to understand the way science progresses. And, you know, as you said, you know, it’s progressed, it progresses with technology as new technologies come into the forefront, new questions, open new areas open up. And once you appreciate that, it really can help drive the way that you, you know, the kind of science that you choose. And you know, basically with, I mean, I had already known with monoclonal antibodies that proteins are moving all over the place. And, but we didn’t have microscopes to allow you to see this. And it was only with GFP that and initially I wasn’t, nobody was thinking GFP could, you would want to use it to look at anything moving around.

Jennifer Lippincott-Schwartz (00:30:50):
But when my first graduate student got a hold of the clone from Martin Chalfie and we put it on to a golgi enzyme, and I’ll never forget looking under our inverted microscope at the golgi, with the fluorescent GFP tagged to its enzyme. And I saw things moving from the, it wasn’t just localized at that golgi. There were things sort of peeling off of that structure that I realized we need a better scope. If we’re gonna, you know, this, we can look at the, you know, we can’t, you can’t just take snapshots of this thing on your Polaroid camera. You need a different microscope. And it was at that time that I just said, okay, I’m at NIH, there is one confocal microscope on this campus, a BioRad. And I know I went over and worked with Mark Terasaki who had that microscope.

Jennifer Lippincott-Schwartz (00:31:49):
And we started taking movies time-lapse movies of the GFP that was introduced either into the ER or the golgi. And then that’s when we very quickly realized and this was just complete serendipity. But when we were, you know, watching, you know, taking movies and stuff, we suddenly started thinking GFP was touted as a fluorophore that didn’t bleach, you know, that’s why it was so, so much better than fluorescent dyes. It did not bleach. And we just, you know, I said, okay, well, I don’t think anything does not bleach, you know? And so we decided, let’s see if we can try to bleach this molecule in a living cell. And so to do that, we essentially, we essentially put full power zoomed up at a small spot on this scope small spot of the golgi and wiped out the fluorescents there.

Jennifer Lippincott-Schwartz (00:33:02):
And, you know, I was happy. Okay, cool. GFP does fluoresce does photo bleach, but what was mind boggling is the because we had it on a time lapse imaging mode, a few sequences, it started recovering. And at the thing that was so incredible was that I realized nobody including ourselves, we’re thinking about molecules diffusing in the cell in membranes of a cell. And that, that was transformative to me. I mean, that was like, Whoa, you know, this is not what I’m thinking about. And I realized instantly, this is significant. This is a technology that can open total windows into how proteins are anchored in different places in the cell. And so for the next three or four years, basically we pushed that sort of constant conceptual approach. And it was not met. I mean, people couldn’t question it, which was awesome.

Jennifer Lippincott-Schwartz (00:34:11):
I mean, so that’s really cool is when you have some thing that you cannot question but there were some real, you know, people were not happy in some respects because for instance, in the case of the golgi apparatus, everybody assumed that the way molecules were retained within that organelle was by being anchored, immobilized in some fashion. And we showed that they were moving like mad. So that meant there had to be some other mechanism that was retaining these proteins in the golgi apparatus. And to this day, it’s still debated how molecules are retained within that organelle.

Peter O’Toole (00:34:56):
So you’ve been at the forefront of quite a lot of new technologies as they came through and obviously with the a photo activated fluorescent proteins, which, which is mega, which actually ended up with Abbott getting his Nobel prize for that. Yeah. I think it was your seminal paper that was underpinning that. Where do you see the technology going in the future? Where’s the unmet needs.

Jennifer Lippincott-Schwartz (00:35:18):
Yeah. it’s going in a lot of different ones. Yeah. It’s Yeah, it’s interesting. So sometimes you can’t anticipate where that technology’s going, unless you’re doing the technology. And then you start seeing things that you hadn’t appreciated before. Like, you know, with that with a photobleaching I wasn’t, you know, it’s like, that’s not something that we pre fabric, you know, thought ahead of time that that was where we’re going to go. And the same with the photo activatable GFP. The reason why we, and this was George Patterson in my lab who really said, I want to make a photo activatable GFP. He wanted to make a better way to do photo bleaching by photo activation and that, you know, it worked beautifully. And then suddenly you realize that you can do a lot of things with that and a single molecule photo conversion to, you know, to track individual molecules and to perform technology, you know, techniques like PALM and STORM.

Jennifer Lippincott-Schwartz (00:36:45):
That was not something that we were thinking about at all, but, or bet sick soul immediately with the publication of our photoactivatable GFP paper, what it could be used for from that perspective. So the way that these new technologies are sort of developed is really interesting from a sort of sociological point of view. It’s frequently not you know, individuals take it one step and then it’s other individuals that come in and see, you know, see different directions where it can go. And basically, that’s, that’s how I’ve been part of this whole system is I’m in a place where, you know, I’ve been, I positioned myself somehow in to situations where you start seeing connections between different technologies. Like right now, we’re really excited about using focused, ion beam, scanning, electron microscopy,udeveloped,uusing the approach that Harold Haas at Janelia has been promoting where you’re using focused ion beam as a milling mechanism, and you combine it with,uscanning EM to be able to see a very high,uisotropic resolution, everything within a cell.

Jennifer Lippincott-Schwartz (00:38:21):
And combining that with technologies that allow us to look at how individual proteins are distributed is pretty exciting. And at cryo temperatures so that you have, you know, optimal staining and optimal visualization of these probes. So looking at new probes for pushing that is very helpful you know, we’ve recently been able to see that we can use fluorescent dyes in a very productive way at these cryo temperatures to do correlative work in these electron microscopy regimes. But you know, it’s sort of like I’m going back and forth in terms of spatial temporal resolution. That sort of goes way down, but then, you know, there’s a lot that you can get by coming back out with the dynamics, the dynamics are, are also mindblowing, you know, there’s almost like a yin yang between improved spatial resolution versus improved temporal resolution

Peter O’Toole (00:39:38):
Still expanding, is maybe the right word, but they’re both developing, it’s such a pace at the moment and also single cell technologies to start correlating these with metabolites or going through and looking at the transcript like, do the High-Plex imaging that this huge areas. It’s a massive jigsaw that we’re creating. And the data analysis is I think going to be a real challenge. I just, you’re just, you’re FIPSE and vendoring the volumes is a massive challenge doing the actual data analysis and making sense of it, statistically, it is it’s going to be really difficult to do. I want you to pull up all this work that you do. How did you balance that? We just, you can’t, you’re not all work work work. So obviously we’ve heard about Selden Island, but what else do you do in your spare time, is it, what do you enjoy doing just to get out of work?

Jennifer Lippincott-Schwartz (00:40:34):
Yeah, yeah. Well, right now I’m out of work, which is actually pretty fun in the sense of being home and not having to, you know, commute to work. But yeah, totally. It’s a a challenge to you know, keep things moving in this kind of environment when your postdocs are locked at, you know, in their own environments. And I mean, fortunately when this Corona virus hit us there were many, the people in my lab were very well suited for putting papers together and stuff. So we’ve been working hard at that level. If.

Peter O’Toole (00:41:23):
This isn’t working hard.

Jennifer Lippincott-Schwartz (00:41:24):
No, exactly. So that was in March.

Peter O’Toole (00:41:29):
What are you in this picture, Jennifer, where are you?

Jennifer Lippincott-Schwartz (00:41:31):
So I’m actually on Potomac on the the there’s a trail along the Potomac on the Maryland side. And it’s called the Marston track. And I like going there at least once a week. This is when the bluebells were out. It’s just magical. It was just absolutely beautiful. And yeah, that was in March it,

Peter O’Toole (00:41:58):
Gosh, your bluebells are much earlier than ours, bluebells in April, April? Yeah, usually April two through to mid may and unfortunately I got injured running but we usually go through some gorgeous bluebell woods and by the time I could get out and because of lockdown as well, I couldn’t drive there. And I said, by the time we got there, they were all fading. Oh, I missed it this year.

Jennifer Lippincott-Schwartz (00:42:22):
That’s too bad. That’s too bad this year. Cause normally I get so mad because it’s the, it’s the end of March and the beginning of April when these things come out and that’s a horrible travel time for me. I mean like very bad travel where I’m gone every weekend, almost, you know, with some sort of trip one way or another. And you know, I would, in the previous few years, you know, I’d only be out there once to be able to see them, you know, and it would be either too early, too late or during this lockdown I could go every other day. It’s just, you feel like you’re on a fairy land and it’s stimulating it really stimulates your mind.

Peter O’Toole (00:43:10):
I know you’re a fellow runner as well, so I believe you’re also into plants and list that now as a hobby.

Jennifer Lippincott-Schwartz (00:43:20):
Yeah. I mean, it’s sort of what I love. I love plants because you know, they’re visually stimulating. But also it puts, it makes, makes me, it takes you away from your own self. It takes you away from the narrow perspective of humans. And the world you know, this earth is a big place that has a lot to it than just homo sapiens. And I like thinking a lot about that. And, you know, I like thinking about the origin of life. I like thinking about how cells came about the origin of eukaryotic cells and plants and the way that all of these systems are coordinating with each other in a co you know, in a, in a feedback system is, is just so mind boggling and yet fundamental to our ability to be successful on this planet. And yeah, so that’s, that’s really, that has sort of plants I’m becoming much more impressed with because they are, and we eat them and lots of other animals eat them without that. We don’t have a way to get any kind of metabolites. So

Peter O’Toole (00:44:55):
Am I correct in remembering that it’s actually herbs that you you’ve got a fondness of when it comes to the different plants.

Jennifer Lippincott-Schwartz (00:45:00):
Yeah, well recently, yes. Yeah. And actually, yeah, the herbs become interesting because you realize you know, the, the Corona viruses, obviously on everybody’s mind and we have no treatment for this thing zero and you know, it’s partly is, you know, the, the virus itself has a complex life cycle, but it’s impacting, it’s creating a whole feedback system in the body that, you know, is impacts all kinds of things, your immune system, you know, the way your kidney and liver, et cetera, functioning, and you know, modern doctors, you know, they’re treating each one of these things separately in these, in these patients who come into them. And we know that, I mean, this is only the knowledge for that has only been acquired over the last 60, 70 years. Whereas humans have been dealing with viruses for thousands of years and they way they deal with these viruses as do animals is by eating particular types of plants, herbs, and other things. And so it’s made me super interested in trying to understand what is it about these herbs that are giving the sort of health benefits. And not that I can, I mean, I am zero, you know, sophisticated in this, but it’s something

Peter O’Toole (00:46:39):
Because you seem very sophisticated. If I, if I asked you what herb, this is,

Jennifer Lippincott-Schwartz (00:46:43):
I want to smell it.

Peter O’Toole (00:46:44):
You know, go, go, go, go, go for a sniff.

Jennifer Lippincott-Schwartz (00:46:46):
Yeah. Yeah. Basil

Peter O’Toole (00:46:50):
I it is, that’s a good spot. I do know. I can’t remember exactly what it is, it’s not the broadleaf basil, its very fine. Leaf, I think a Greek type basil, very very pungent. Wow. Very pungent.

Intro/Outro (00:47:05):
What do you put it in? What do you put it in tea or

Peter O’Toole (00:47:08):
Generally tomato based sauces, things like that, so pasta sauces good tinned tomatoes. Yeah. Chopped tomatoes and plenty of the basil in it. It might be a bit too strong for pesto, but certainly for the sauces. It’s great. Yeah.

Jennifer Lippincott-Schwartz (00:47:24):
The other thing that’s so interesting about these herbs and plants and stuff like that. Yeah. They’re super good for you. I mean, you know is, you know, we know so little about the physiology of our health systems. I mean, one of the things that I’ve become interested in you know, I’ve been a, a cell biologist that has really used just tissue culture type cells to analyze how things are operating within these cells. And seeing now that we have technologies that will allow us to actually see the way cells are interlocking with each other at very high resolution in tissues. It now makes you start thinking that we are poised for beginning to understand the way cells are working in the context of specific tissues and every environment. Yeah. And, you know, feedback between that, you know, like the way that the nerve, the, how different tissues communicate with each other, your nervous system communicates with your gut and your stomach, and that’s all interlinked. And these herbs and these plants trigger those systems. Anyway, I don’t want to talk to me about all this, but anyway, I like thinking about it. It’s fun. That’s what I do when I’m trapped at home,

Peter O’Toole (00:48:57):
Where do you make, where do you do most of your thinking? Is it whilst you’re out walking or is a home, is it in the bath? Is it when do you do?

Jennifer Lippincott-Schwartz (00:49:05):
Not in the car? Not now. Yeah, I think it’s usually when I’m either out walking or you know, I do a lot of if I’m writing, I’ll think if I’m writing a paper and I’m, I mean, it’s really fun to write papers and really get into the literature and you start trying to connect things. You start thinking hard about that and then reading, reading books.

Peter O’Toole (00:49:42):
Yeah. I was actually did do what, what’s your preference? TV or books?

Jennifer Lippincott-Schwartz (00:49:49):
It can vary. I mean, usually books, TV, sometimes I’ll splurge. I’ll do TV if I’m totally wiped out.

Peter O’Toole (00:49:57):
Yeah. So drama factual. Do you binge watch a box set? What do you watch on TV?

Jennifer Lippincott-Schwartz (00:50:05):
Okay. Let me think. Well, I just actually I watched, I was in an exhausted mode a few weeks ago when I started watching Outlander. Yeah. But I stopped watching that. It’s just way too violent. After a while, and I then started realizing each episode was just, you know, increment, it wasn’t as complex and rich in the way that I wanted it. But I recently picked up an a book written by Herman Wouk in the seventies called Winds of War. I don’t know if you’ve ever was a huge bestseller there. And it’s about the, the World War II, essentially entry into World War II and World War II itself. And all of these you know, from it’s a, it’s a fictional novel, but from the perspective of a family that was involved in a family that is, you know, has the head of the family is a military officer, but he ends up, you know, he interacts with Hitler, Lenin Hitler, Stalin Churchill Roosevelt, and you are reading the interactions of him with these people.

Jennifer Lippincott-Schwartz (00:51:28):
And you see the perspective of all of these different players at the onset of World War II with all of the horrible, you know, challenges during that period. And it it’s just, it was just very cathartic because in many respects, we’re in a, in a very difficult period right now in terms of what’s happening across the globe and in the same way that people during that period, individuals during that period had very limited potential to do anything. Things just were, you know, things were unfolding. People did not know, you know, that Hitler was going to invade Russia. You know, they didn’t, you know, they didn’t know Hitler was going to invade Poland. You didn’t know ahead of time what was going to happen. And so in the same way that we do not know right now, what’s going to happen with this Corona virus, you know, we’re about to face a total economic depression across the world, especially in the United States.

Peter O’Toole (00:52:42):
I don’ think it’s just the States, I think that’s that’s global. Yeah.

Jennifer Lippincott-Schwartz (00:52:46):
And what does that mean? You know, we don’t, we don’t, it’s hard to think in the future and you know, what’s going to how the future will unfold itself. And so reading this book brought that into very tight focus and it was super exciting because you were educated about the whole, the whole world, the world during that period. So anyway, that’s so much fun to read something like that.

Peter O’Toole (00:53:17):
So much fun, but that was really cheery

Jennifer Lippincott-Schwartz (00:53:21):
I don’t know. For some reason. It it wasn’t. Yeah, no, it’s not so depressing because it makes you, well, you realize it’s an important time that, you know, it’s an important time that we need to take seriously, that we have to have people who are in charge, who are people who, I mean, you realize how important it is to have leaders that are smart and listen to you know, experts and, you know, can, can make good decisions. But at the same time, things unfold that you can’t predict. And yeah, no, it’s,

Peter O’Toole (00:54:07):
There’s a huge unknown to cheer things up. I’ve got one more picture that I think you sent, and I have no idea what this picture is about, but I can see a monkey.

Jennifer Lippincott-Schwartz (00:54:18):
Yes. That’s a chimpanzee. Yeah. That’s a baby chimp. Yeah. And that’s me with my daughter Leanna. So Leanna went to Cameroon as a peace Corps volunteer. And this was during a trip where my husband and I as well as my other daughter went to visit her. And she took us to this island where they have created a sanctuary for baby chimps that have been abandoned or, you know, their parents have died or whatever. And these chimps are grown up to about age five. And then they’re taken to another island where there’s a whole bunch of wild chimps, adult chimps, adult chimps. We also went to that island. You do not get off. Adult chimps are scary. They are, they’re smart and scary

Peter O’Toole (00:55:15):
These aren’t on Selden Island that that’s not why you don’t go there in the dark.

Jennifer Lippincott-Schwartz (00:55:20):
These guys were the cutest things. And the, it it’s truly amazing how smart they are. They’re just like little kids. They you know, I had a sneaker on and I tied my sneaker and they, there were three of them that just immediately ran and immediately kneltdown and just watched what I was doing as I was tying my shoe. And at one point, I can’t remember I took off the shoe to show it to one of the chimps cause you know, they were, you know, they were humanized, so they were not afraid of humans. And that chimp took the grab, you know, Suzy had the sneaker, he ran up into a tree with it and I was thinking, Oh my God, I’ll never get this sneaker back then when we watched him up in the tree, he was trying to tie the shoe. It was, it was unbelievable. It was like a little kid who was trying to, you know, do exactly what I was doing, what I had done. He was trying to, you know, and then ultimately we were able to distract him and he came down and I got my shoe back. But it, it it’s if you, have you ever been on a Safari in Africa?

Peter O’Toole (00:56:45):
Yes. Down in Zimbabwe , but, but not that up close. He was, he was quite a wild Safari.

Jennifer Lippincott-Schwartz (00:56:50):
Yeah. Yeah, yeah. It, it it’s truly, I think we don’t understand. We don’t appreciate the, the knowledge that animals have their intelligence. It’s, it’s profound. And so that was fun. That was like, wow, fun.

Peter O’Toole (00:57:10):
I’ve got, I think we’ve just got a few minutes left there. Are there any key points I notice you’ve done a lot. You were president of ASAB, so big societies getting involved in other activities outside of the main workplace, such as ASAB, how important do you think those sorts of activities are?

Jennifer Lippincott-Schwartz (00:57:29):
I think they’re really important. I think it’s really important to know your scientific community. You cannot do science in a vacuum. You need to understand that your, the knowledge is part of a broader understanding of people and those people all have to share like a common language, a common thinking about a system. I mean, were are you? You know, and you know, when, especially if you have, there are a lot of times when people have very different perspectives for how something works. And it’s only when people, when people come together that they can actually share those different ideas. And you know, you can come to an agreement and move forward in terms of the understanding. I mean, I remember when I was a graduate student being so excited when I went to these meetings, especially small meetings where you can hear people talk to each other big, the big shots, sort of the kinds of questions that they were asking. And that was so important for me because it allowed me to understand what the questions were in the field. What is it that people really did not understand? It’s very hard to get that information from just reading papers. I mean, you know, people say, Oh, it’s not understand this, that, and the other thing, but you don’t really understand the depth of that knowledge or lack of knowledge in a particular area, unless you hear it from people who are actually talking about that science in a, in an open dynamic way.

Peter O’Toole (00:59:30):
I think that’s, I actually chimed with a lot of common thoughts. Actually, I it’s been lockdown has changed an awful lot of things. The way we behave, the way we’re interacting with people, we’ve hosted lots of large forums with up to three hundred people. And we were interacting really well, but I don’t think that that is sustainable because I think the younger generations coming through, they need that face to face networking opportunity that eating, eating together, drinking together, having that social time to really get to understand people and to hear new ideas, to think of new ideas or inspiration.

Jennifer Lippincott-Schwartz (01:00:08):
Totally. I mean, the, it was only when my postdoc George Patterson, I took him to a Gordon conference with me where he was presenting his work using photobleaching that he realized that people were not willing to accept some of his conclusions because he was not, it wasn’t as compelling as it could be. And he realized the only way he could convince them was to create a photoactivatable fluorescent protein. And it was that motivation. It was, you know, seeing people and having people question what you’re doing and realizing that if you’re, if, if you think you’re right, you gotta take it to another level. And what is the level that, that would be acceptable in the community in terms of technology, et cetera. So all of this is really important. These sorts of interactions are fundamental for the way that science has progressed in the past. And you know, it would be very sad if we did not have that, able to come back and flourish the way it has in the past. Cause yeah, zoom calls are good. And definitely, you know, sometimes I’m going to be doing a virtual meeting in a month and you just realize how much time and energy, you know, money is saved by people just popping onto their computers from their home, but there’s a lot that’s missing.

Peter O’Toole (01:01:52):
Couldn’t couldn’t agree more. I have two more quick questions for you. First one, actually, it’s a really odd one. What is your favorite publication that you’ve done? It may not be one of your mega papers. It may be a smaller paper. Which one are you most proud of as a publication?

Jennifer Lippincott-Schwartz (01:02:11):
Well, there is a paper that we published in Journal Cell Biology many years back that I was very proud of in terms of the way we wrote it, but also in terms of the quantification basically we were quantifying secretory trafficking using fluorescent, we fluorescent GFP of different cargoes that were moving through the secretory pathway. And we were correlating the fluorescent intensity from our images to an actual number of molecules. And in addition to sort of doing that, we were we quantified the different steps in that pathway from the framework of, of rate constants. And what that immediately led us to realize was that the rate constants were not changing based on how much cargo we had, which meant that the way cargo was moving from one place to another was mass action, which was not what people had thought.

Jennifer Lippincott-Schwartz (01:03:27):
And that has huge implications for the way that the whole machinery that’s regulating the secretory traffic pathway works. So for me, that paper was really, I mean, it took a long time to get together to, you know, to put it together. And it involved interacting with some physicists because we needed to interpret, you know, what these rate constants meant and also modelers. So we had this paper was modeling of, of these different steps. So, you know, there was a lot of things that were happening. There was modeling, there was physics involved. And then just basic cell biology,

Peter O’Toole (01:04:11):
Very very interdisciplinary.

Jennifer Lippincott-Schwartz (01:04:13):
Yeah. And it was so much fun because of that. You know, hours on phones, you know, with physicist at Rockefeller, you know, a modeler, you know Bob Ferer who works out of his own company, his own home sort of thing. And yeah, it was just, it was really fun. So that I would say that’s one of my

Peter O’Toole (01:04:36):
Favorite publications. And one last question is any advice you’d give anyone in a PhD or early postdoc career,

Jennifer Lippincott-Schwartz (01:04:46):
I would say, just keep up the spirit, you know don’t give up you know, it, and don’t worry, that’s I think a really important advice you know, frequently, you know, sometimes these with postdocs, we over worry them with, Oh, you need to be trained to do this and that. And the other thing, and that continually reminds them of their inadequacies and makes them have to compare themselves with people who are, you know, who’ve been PI’s for 20 years or 10 years, and, you know, people grow there’s, you, you tend to compare yourself with somebody who’s 10 or 20 years ahead of you. And you don’t realize that they’ve been at it for 20 years or 10 years. And so of course they know what they’re doing. Everybody who starts out has a similar sort of degree of ignorance and you know, is going to make mistakes and, you know is gonna, you know, be scared and have a hard time.

Jennifer Lippincott-Schwartz (01:06:01):
What’s important is to just love what you’re doing. Love the science focus in on the questions that you’re interested in and don’t worry about, am I going to really get this job? Don’t have to make this decision or that, you know I mean, that’s just, that’s been my philosophy, but yeah. And it’s worked. Yeah, no, exactly. What’s the opportunities come to you,

Peter O’Toole (01:06:30):
Follow those, follow the opportunities where they’re right for you and follow your strengths. And I like the advice earlier as well about not being intimidated by giants in the field, as you showed today the giants, are very personable, normal people who like all sorts of things, just, just normal people to approach at networking opportunities are great. Great advice, Jennifer. I think we’re up to time now. Thank you so much for joining me today. It’s been really.

Jennifer Lippincott-Schwartz (01:06:58):
This is really been fun. Very good.

Peter O’Toole (01:07:01):
I will hopefully see, you properly.

Jennifer Lippincott-Schwartz (01:07:05):
I look forward to it. Yes.

Peter O’Toole (01:07:07):
Again, to the future, Jennifer. Thanks very much. Thank you.

Jennifer Lippincott-Schwartz (01:07:09):
Thank you. Bye.

Intro/Outro (01:07:14):
Thank you for listening to The Microscopists, a Bitesize Bio podcast, sponsored by Zeiss Microscopy. To view all audio and video recordings from this series, please visit bitesizebio.com/the-microscopists.

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