Teuta Pilizota: The itch that drives research
Today in People Doing Physics, we’re delighted to welcome Professor Teuta Pilizota, a physicist who works at the intersection of biology, chemistry and physics. Having set up her first lab during her PhD, Teuta is no stranger to the challenges of moving a lab, and she recently brought her innovative biological physics work to the Cavendish Laboratory.
Teuta brings a unique perspective to science. She’s someone who finds the complexities of maths more straightforward than those of human nature, and who will choose excitement over logic when selecting scientific questions to research. Her curiosity drives her to scratch the surface of living matter, and to seek out new physics that is not yet understood.
Together today, we talk about resilience, patience, perseverance... and what to look for in the basement of a physics lab.
Stay with us.
Useful links
- Learn more about Teuta's research: Prof Teuta Pilizota and her start-up company OGI Bio Ltd
- To learn more about the Cavendish Laboratory, or if you are interested in joining us or studying with us, go to the Cavendish website.
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Episode credits
Hosts: Charlie Walker and Vanessa Bismuth
Recording and editing: Chris Brock
This podcast uses the following third-party services for analysis:
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Transcript
It's like an itch.
Speaker A:Like certain problems that I wish to solve just bother me.
Speaker A:They come out of nowhere, and for some reason, I want to find the answer to them, and I can't forget them until I solve them.
Speaker A:And that is really what, for me, drives research.
Speaker A:Right?
Speaker A:It's literally you feel like you need to scratch, and until you scratch it, you can't let go.
Speaker B:Welcome to People Doing Physics, the podcast that explores the personal side of physics at the Cavendish Laboratory, the University of Bridge.
Speaker C:Hello, I'm Charlie Walker, an astronomer at Cavendish Astrophysics.
Speaker B:And I'm Vanessa Bismuth, communications manager at Cavendish.
Speaker C:Today in People Doing Physics, we're delighted to welcome Professor Teotepilizotta, a physicist who works at the intersection of biology, chemistry and physics.
Speaker C:Having set up her first lab during her PhD, Toyota is no stranger to the challenges of moving labs, and she recently brought her innovative biological physics work to the Cavendish Laboratory.
Speaker C:Toyota brings a unique perspective to science.
Speaker C:She's someone who finds the complexities of maths more straightforward than those of human nature, and who will choose excitement over logic when selecting scientific questions to research.
Speaker C:Her curiosity drives her to scratch the surface of living matter and to seek out new physics that is not yet understood.
Speaker C:Together today, we talk about resilience, patience, perseverance, and what to look for in the basement of a physics lab.
Speaker C:Stay with us.
Speaker C:So welcome.
Speaker C:Teresa, thank you for being with us today.
Speaker A:Thank you for having me.
Speaker C:So, as always, let's start at the beginning.
Speaker C:Your childhood and early education took place in Zagreb.
Speaker C:Could you tell us a little bit about what you liked at school and what you didn't like?
Speaker A:So I liked, at school, I liked primarily math.
Speaker A:That is one thing that I clearly remember liking.
Speaker A:I did well in other subjects, but it was just quite straightforward to memorize.
Speaker A:So I can't say that I particularly liked them.
Speaker A:I like drawing as well, but I like math more than I like drawing.
Speaker A:I found math very calming.
Speaker C:And do you think that your interests were influenced by anybody, perhaps your parents?
Speaker C:Can you tell us about what they did?
Speaker A:So my mom is an architect and my dad is a mathematician who later moved into informatics.
Speaker A:I think I was influenced by my mom in that I thought quite rationally as a child.
Speaker A:If I'm good at math, I'm good at drawing, I should be an architect.
Speaker A:And that's pretty much where I stopped thinking about what should I do with myself in the future.
Speaker A:It was kind of like solve problem, so I didn't sort of pay attention to whether I like something and where I should take it into career.
Speaker A:I would like something and do something, but didn't really think about it as a career choice because that I already ticked off.
Speaker C:But you did mention as well that you.
Speaker C:You didn't really like biology.
Speaker C:Could you expand on that?
Speaker A:Oh yeah.
Speaker A:I didn't particularly like biology at all.
Speaker A:Why not?
Speaker A:Although I love the people who taught me biology, the two professors, they were fantastic.
Speaker A:Well, first of all, I thought that I had all the diseases that we ever studied about.
Speaker A:And second of all, it was just a lot of memorizing, so there was nothing intriguing about it, but.
Speaker B:So you were setting off to become an architect.
Speaker B:But clearly, if we're talking today together, that has changed somewhere.
Speaker B:Could you tell us more about that change?
Speaker B:When happened, what happened?
Speaker A:Yes, certainly.
Speaker A:So it changed two weeks before the entrance exam to the architecture department, where I was preparing for it.
Speaker A:You had to prepare the math exam and a drawing exam.
Speaker A:And I think there was something else like history of Art.
Speaker A:And I was drawing.
Speaker A:I remember I was drawing a chair in my room and I realized that I don't want to be drawing for the rest of my life.
Speaker A:And this was then like, okay, what do I.
Speaker A:And it was the first time where I went back to think about what I actually like now, having discovered that I don't want to be an architect.
Speaker A:And I realized that, well, I really liked math and I actually liked physics.
Speaker A:I was part of a lot of having grown up in Eastern Europe, a lot of these competitions that are organized on a city school and then later Olympics level.
Speaker A:So if you're good at it, you get sent, even if you don't think of it as a career path.
Speaker A:So as part of that, I did one that was experimental.
Speaker A:I was looking at diffraction of gold beads with a heme laser, which is something that I still still do in the lab.
Speaker A:I really enjoyed that.
Speaker A:So I decided that this is probably what I should be doing.
Speaker A:However, I haven't prepared for the entrance exam.
Speaker A:So I went to the department of physics and I said, what do I need to do?
Speaker A:It's like only a couple of weeks probably.
Speaker A:How does the entrance exam look?
Speaker A:Looks like.
Speaker A:And they looked at my grades and then looked at all these physics and math competitions that I've done.
Speaker A:And they said, you, you do not need to do an entrance example to stay take.
Speaker A:And this is how I ended up in the business department.
Speaker B:And so you made that decision in the course of two weeks and you did a swap?
Speaker A:Yeah, it was a total swap, but it didn't feel like it didn't feel as drastic as that.
Speaker A:And with the first two years of the university, I absolutely loved it.
Speaker A:I thought this is the right decision.
Speaker A:The fact that I'm just surrounded.
Speaker A:It was still mostly math the first couple of years and then with a sprinkle of physics and everybody talking just about that, I thought like, okay, this is great.
Speaker B:So you started a four year undergraduate degree in physics in Zagreb and then you did a diploma thesis.
Speaker B:At the start of your degree, did you know which topic you were interested in and which you weren't?
Speaker B:What you were originally seeing yourself doing?
Speaker A:If anything, it kind of came slowly.
Speaker A:I don't think originally I was thinking about what I might be doing later.
Speaker A:I think I just enjoyed the first two years.
Speaker A:I didn't know that astrophysics was not something that I was that interested in.
Speaker A:And I knew that because quite a few others in the class were.
Speaker A:And I found interesting that when we were talking about it, I just always thought it's overwhelming, it's too far, I can't even go there.
Speaker A:So it was kind of like I knew that it was a bit like it felt overwhelming.
Speaker A:So I knew that this is not going to be the direction I'm going to go into.
Speaker A:And later on in like third and fourth year, I heard about some of the like molecular motors and how people were starting to understand biological system in a similar way that we do non living matter.
Speaker A:And I found that very intriguing because I thought, oh, okay, this, this humans and living stuff that I found so confusing maybe actually it can be made a bit more, less confusing and more clear in some kind of mathematical form.
Speaker A:And that I found very intriguing.
Speaker A:So then I started thinking about what I could be doing.
Speaker B:But so did you go straight into the biological physics and you took some detours, didn't you?
Speaker A:So I didn't really.
Speaker A:I still majored in solid state theoretical physics and I took courses that are related to that.
Speaker A:It was also a little bit linked to what was on offer and who, who was teaching the courses.
Speaker A:I took that into account and I did think, well, solid state physics is the right scale that I want to be, but it took a little bit of time to kind of discover what kind of, you know, what is this biological physics or biophysics, what it really is, because there's quite a lot of work, for example, in functional imaging of the brain.
Speaker A:And then I thought, okay, no, no, no, brain is too complex, not yet, right.
Speaker A:So I really, I was fortunate to take part in Lesosh summer school when I was a third year undergraduate and I was Babysat by some of the people who are.
Speaker A:Everyone who was doing something exciting in that field was there.
Speaker A:I knew nothing about them, though.
Speaker A:So I was babysat by some of the.
Speaker A:I'm not sure if they remember, like Ninke Decker, who continue to do beautiful work in that area.
Speaker A:And they were like at a PhD level, postdoc level.
Speaker A:So I really got exposed to what was happening on this level of molecular motors and biophysics of molecular motors.
Speaker A:And I.
Speaker A:That's very, very exciting.
Speaker A:And I met a couple of people that I wanted to.
Speaker A:I thought I could do my PhD with.
Speaker A:One of them was actually Tom Duke, who was at University of Cambridge and a couple of people, Joe Howard, who was then in Dresden in Max Planck Institute.
Speaker A:So I think it was the moment that I realized, well, a couple of weeks that I realized that this is the direction that I would like to go into.
Speaker A:But I was originally thinking that it should be theoretical still.
Speaker A:Then I got convinced that given the amount of data you in the field at the time, it should probably be experimental.
Speaker A:And that also influenced.
Speaker A:Influenced my decision because we were talking.
Speaker B:About what sort of time.
Speaker B:When was that?
Speaker A:This was end of third year, third year undergrad.
Speaker A:So when was this?
Speaker A: Like early, early: Speaker B:And so there was not enough data in the.
Speaker A:There was not enough data yet.
Speaker A:Yeah, it was just.
Speaker A:It was just coming.
Speaker A:The field was just emerging, I would say.
Speaker C:And how did you come to be at the summer school in the first place?
Speaker A:This was.
Speaker A:It was recommended to me by one of the professors in biophysics.
Speaker A:Salma Supek was holding this course and she recommended that I go.
Speaker A:And she convinced me that I'm undergrad, that I should probably take a chance because it doesn't happen as frequently in this topic.
Speaker A:And also I think there was this UN aspect.
Speaker A:So the fact that I was coming from Croatia and filling the quotas, I think that helped as well, to be quite blunt.
Speaker A:So.
Speaker B:Well, any opportunity is a good opportunity.
Speaker A:I do not mind at all.
Speaker C:And you mentioned that the summer school spoke to you in a way that biology at school clearly did not.
Speaker C:So what was it exactly that really seized your.
Speaker C:Your interest?
Speaker A:It was really very simple, that you could put equations to the way these molecular motors walk and produce torque and force and all of that.
Speaker A:It was this quantification of the living system that I found very, very exciting because I find it that when you put equations to something, it's very, very orienting.
Speaker A:You can kind of like almost as if you drew a map to something so you can turn it whichever way around.
Speaker A:And I still feel I know where I am and I understand it.
Speaker A:And I don't feel like that if equations are not there.
Speaker A:I kind of feel like you could, you know, spin me, and then if you stop me at the wrong moment, I will not know where I am.
Speaker A:If there are some equations that describe a system, this doesn't happen to me.
Speaker A:I can very, very quickly orient myself and I feel like I feel really comfortable with this.
Speaker A:It's almost like a level of calmness when that happens.
Speaker A:There's like a, you know, something when you don't understand.
Speaker A:It's almost like an itch you need to scratch.
Speaker A:And when you do understand and you formulate it in mathematical form, it's a sense of release.
Speaker B:And so was that a discovery that you could actually talk about biology?
Speaker A:That's precisely what, what the discovery was.
Speaker A:Okay, this.
Speaker A:This could work.
Speaker A:So.
Speaker A:So, yeah, that and the fact that we could do more and more of that and some of this, you know, a confusing world of living beings could become a bit more comprehensible.
Speaker A:That was what I found intriguing and exciting.
Speaker C:So this might also explain the tendency towards theory rather than experimentalism.
Speaker C:Until you were given this extra piece of advice, probably.
Speaker A:But also we have to take into account that I was doing a degree in Croatia, where the science is not that well funded, which means that those who are doing the science and doing it well will be tending to do theoretical science simply for practical reasons.
Speaker A:So it's probably a combination of the two.
Speaker C:And so now you've had a lot of experience with labs and setting them up and moving them around.
Speaker C:So how do you feel about that advice now?
Speaker A:Yes, indeed.
Speaker A:Having a big lab brings all kinds of challenges that having a computer and a pen and a blackboard doesn't.
Speaker A:But I think, yeah, it was the right choice.
Speaker A:And actually confirming seeing the experiments, actually seeing that it does happen is exciting.
Speaker A:I would also say that I learned that there is 101 little thing and little idea that you need to implement to get the experiment to work that you don't even appreciate unless you start doing experiments.
Speaker A:It kind of seems straightforward.
Speaker A:You know, take a bunch of equipment and you measure.
Speaker A:It's not as straightforward as that at all.
Speaker A:There's kind of like, like a lot of little ideas that you're putting in and you're solving it to get the experiments to work.
Speaker A:So I enjoy that.
Speaker B:And so that was it.
Speaker B:You made another decision and to go into biological physics.
Speaker B:And you were after your degree and your diploma, you did look for PhD positions.
Speaker B:Tell us about that stage.
Speaker B:What were you looking for?
Speaker B:Where did you apply to and where did you end up?
Speaker A:So yeah, I applied mostly to people who I met at this summer school.
Speaker A:So I applied to Tom Duke to Cambridge and that was a complicated process because I understood nothing about what colleges are and I had to choose a college and they all had.
Speaker A:The description was lively, common room, lots of green grass and I didn't understand was a common room and what am I supposed to do with a green grass other than sit on.
Speaker A:So once I understood that process I thought okay, I should look at Oxford because probably similar.
Speaker A:So I'm going to capitalize on the time invested understanding the system.
Speaker A:So I did and I found another person in Oxford who was doing molecular motor.
Speaker A:His name was Richard Barry.
Speaker A:So I applied to him as well.
Speaker A:And then I applied to Max Planck Institute in Dresden and I think I applied to University of Nottingham as well to work with afm.
Speaker A:And then I got called to interview a couple of these places and I selected based on how comfortable I felt in the.
Speaker A:You know, in the building and in the surrounding of where the labs were.
Speaker A:I kind of felt like some of the interviews, the buildings and the rest of the groups were quite bio so I didn't feel comfortable.
Speaker A:I in the end decided to go with Richard Barry in Oxford because I felt like he knows what I know and what I don't know and the kind of science I feel comfortable with and what I will need to.
Speaker A:What I will need to learn.
Speaker B:Yeah, so what do you mean by that?
Speaker B:He knows what you.
Speaker A:So because his background was also.
Speaker A:Was also in physics and we were based in physics building and I always joke about this that when some of the buildings that I visited during the interviews they showed us all around the building there was a lot of bio related work like they would have fish in the basement like rows and fish.
Speaker A:And I feel very disoriented because in basements of, you know, keep magnets.
Speaker A:So I guess the message was really that I didn't feel like I made a mistake in terms of what I wish to study.
Speaker A:I didn't want to go and study biology.
Speaker A:I kind of wanted to apply the physics viewpoint onto learning about living matter and I was very aware that I'm going to.
Speaker A:I said that I know very little biology so I wanted to be in an environment where those that I work with appreciate how little biology I know but also who know what I do know and that's how I made decisions.
Speaker B:And there were magnets in Oxford Basement.
Speaker A:There were magnets in Oxford.
Speaker A:Basement of Clarendon lab there.
Speaker A:We need magnets.
Speaker B:All was well in the world.
Speaker A:All was well indeed, indeed.
Speaker C:Fish were on the roof.
Speaker A:Fish were on the roof.
Speaker A:Fish for grill like well done.
Speaker B:You told us earlier that your PhD required a combination of hard work, luck and talent.
Speaker B:Could you explain what was so challenging about your project and what did you have to do in your first years?
Speaker A:I think what was challenging about my project is probably what is challenging about every PhD project, which is that you're trying to find out something new about the world around you.
Speaker A:And that, and you are going the way you go about it is based on what is essentially an educated beta guess.
Speaker A:You don't really know whether you are going in the right direction.
Speaker A:You have advice from those who have even more experience than you.
Speaker A:In my case, more experience than me.
Speaker A:I had very little experience in biological physics, if any.
Speaker A:And that realization is simply hard because it doesn't mean that you exposed to luck by default quite a bit versus when you're an undergrad.
Speaker A:You get given examples that we know how to solve and you need to learn them.
Speaker A:So if you're hard working and you're talented, you're going to do well here.
Speaker A:You can be hardworking and talented, but if you're not lucky as well, it might not go as well.
Speaker A:And handling that element I think is probably what turns you into scientists, but also grown up, I found, because life has that exact component in it as well.
Speaker A:So it's not just the PhD that requires this amount of luck, other things in life as well.
Speaker A:So handling that, handling that uncertainty and potential unfairness that you were not lucky and someone else next to you might have been a lot more lucky is part of what the challenge is.
Speaker A:I also, I was the second student in Richard Barry's group, which was, which was exciting.
Speaker A:So the benefit that I got is that he got to spend a lot of time with me, but it was also a lot of setting up.
Speaker A:And it was setting up the optics lab, but it was also setting up the biology lab.
Speaker A:I learned how to purify this protein rotary molecular motor that I was working in by going to Japan to a lab in biochemistry lab in Japan where I learned the whole purification process and I had to help set it all up back in Oxford in a building that was, had magnets in the basement.
Speaker A:It wasn't a biochemistry building, so they were not.
Speaker A:The equipment was not necessarily there.
Speaker A:So we had to, well, cross buildings and all that.
Speaker A:And that was all challenging.
Speaker A:So setting it all up to even get to the stage where you can do the experiments was challenging.
Speaker A:At the same time, I learned a lot.
Speaker A:I did have an experience of how that all works.
Speaker C:So it was a lot of responsibility setting up a lab for the first time in the first few years of your PhD.
Speaker C:How did you find that?
Speaker C:And was your supervisor very confident in you?
Speaker A:Yeah, he was probably.
Speaker A:Yeah.
Speaker A:I would say that he was too confident in me.
Speaker A:And on my end, I would say that I was just naive.
Speaker A:I didn't think about it.
Speaker A:So great combination.
Speaker A:So.
Speaker A:Yeah.
Speaker A:But I didn't view it as a responsibility in a way.
Speaker A:Right.
Speaker A:Okay.
Speaker A:These are the things I need to do to get to the place where I wanted to be.
Speaker A:So I just kind of like, you know, plowed through it.
Speaker A:Yeah, the project.
Speaker A:Keep going.
Speaker A:Yeah, yeah, yeah.
Speaker A:So.
Speaker C:And the lab is still there today?
Speaker A:The lab is still there today.
Speaker A:Yeah.
Speaker A:Well, like, the Microsoft that I built got disassembled.
Speaker A:I think I might have even gotten an email from Richard to tell me that it's going to be disassembled.
Speaker A:Richard is very kind.
Speaker A:Yeah.
Speaker A:But the room is still there and the lab is still there, and there is a different microscope in it.
Speaker C:And you go back.
Speaker A:I do go back.
Speaker A:I went back for.
Speaker A:I kind of perceived the lab is where I grew up to be a scientist.
Speaker A:And I perceive my PhD supervisor as a science dad.
Speaker A: And I went for sabbatical in: Speaker A:I tried to do something that didn't fully work as part of my PhD.
Speaker A:So I tried to do it again, and this didn't work either.
Speaker A:But it led to some other interesting things, and it was also good to be back.
Speaker C:So then after the PhD in Oxford, it was time to choose a postdoc.
Speaker C:And you mentioned that you're thinking about multiple places.
Speaker C:Japan and the US were two of them.
Speaker C:So could you tell us a little bit more about that and that decision?
Speaker C:What did you choose to do?
Speaker C:Where did you choose to go and why was that?
Speaker A:Yeah, so, yeah, so I wanted to get an experience in US to see how a completely different system works.
Speaker A:But at the same time, there was a lab in Japan from Hiroyukinoji who just got set up, who was in this absolutely beautiful experiments on this rotary motor that generates ATP in living organisms.
Speaker A:I was considering going to that lab.
Speaker A:I went to visit, and they had everything there, all the microscopes that you could dream to be able to do that work.
Speaker A:And I like working hard, so I like the environment.
Speaker A:And they grilled fish really well.
Speaker A:So, yeah, that Was it was really a place that I wanted to go to.
Speaker A:At the same time in US I had a look at a couple of labs and identified the lab of Josh Shavitz as the one that I would like to go to.
Speaker A:And I think at the time my original plan was that I first go to Japan and then I come back to us but at the time Josh had the funding and he needed someone to come straight away.
Speaker A:So I was okay.
Speaker A:I think I've seen all the places that I would like to go to in US and I'm not sure it's going to change in a year or two that much.
Speaker A:So I in the end decided not to miss the opportunity and to go to go to US I was also advised that from the career perspective, going just in Japan, just to Japan for postdoc might not be as.
Speaker A:As optimal.
Speaker A:Although I disagree with that advice nowadays.
Speaker A:I think that would have been completely fine.
Speaker A:But I had absolutely fantastic time in the US as well.
Speaker A:I ended up in Princeton, New Jersey.
Speaker C:So did you work very hard and eat lots of grilled fish?
Speaker A:I danced a lot of salsa.
Speaker A:I did eat grilled fish as well.
Speaker A:One of my friends from salsa worked in a fish shop.
Speaker A:So there you go.
Speaker A:There is a fish team all the way through.
Speaker B:So how was Princeton?
Speaker A:Princeton was.
Speaker A:It was a different way of working compared to Oxford.
Speaker A:Not drastically different, but there were certain elements that were done differently.
Speaker A:I think I'm one of the Europeans who came more with kind of like sometimes Europeans have a bit of a negative view of us on average, I would say obviously it varies and I think I was the one who went relatively neutral, maybe with a bit of a negative viewpoint when it comes to healthcare and some of like Social Security.
Speaker A:But I ended up having a great time and actually having a positive, more positive viewpoint after the experience.
Speaker A: here just for context between: Speaker A:To clarify that bit.
Speaker C:Right.
Speaker A:And yeah, I really like the attitude towards work.
Speaker A:I like again that they place work as highly valuable.
Speaker A:They work hard and I like the positive attitude.
Speaker A:Although you kind of feel that everything awesome is a bit, you know, sometimes is a bit like, you know, a bit maybe fake, but it's just very energetic.
Speaker A:Awesome.
Speaker A:Awesome, awesome.
Speaker A:So.
Speaker A:So yeah, when I moved back, I did miss the US attitude towards.
Speaker B:And in terms of the research with the project, how was it?
Speaker A:What did you do when you go.
Speaker A:I started working again on in vitro, some of the in vitro work on proteins from one of the bacterium that we have been studying a lot.
Speaker A:And it's probably the most studied bacterium, Escherichia coli E.
Speaker A:Coli.
Speaker A:So the idea was that I will purify this protein that is a cytoskeletal protein.
Speaker A:And as a cytoskeletal protein we thought it was going to be structurally stabilizing the cell.
Speaker A:So I was going to purify and measure it in vitro what kind of mechanical properties it has and then link that with how it is geometrically positioned in the cell to get almost like a skeleton view of the mechanics of the cell.
Speaker A:But in the process I discovered some things that didn't really fit that picture.
Speaker A:And I was working in vitro with these proteins and I think if at the time there was a group that was working on biochemistry with expert biochemists, they would have probably recognized that I was seeing a signature of this protein being attached to the membrane.
Speaker A:Except that there was no one that we talked to at the time.
Speaker A:Later on there was someone actually from Cambridge who discover that this protein indeed binds to the membrane and that the way we view what it does changed in accordance to that.
Speaker A:So I kind of had all the ingredients to see that, but we didn't see it.
Speaker A:So I guess this goes sometimes to say when someone who is a non expert looks at a topic, it can come with a very, very fresh view.
Speaker A:And sometimes they just don't know what they're looking at.
Speaker A:It depends.
Speaker A:In this case, I was the one who didn't know what she was was looking at.
Speaker A:But I did as I was doing that and I couldn't make sense of it.
Speaker A:I did look at a different regulatory mechanism of this E.
Speaker A:Coli cell.
Speaker A:So during my PhD I worked on also on flagella, bacterial flagella motor, which is a motor that is responsible for the swimming of these bacteria.
Speaker A:So they have about half a dozen of these motors randomly distributed along the cell body and then they all bundle up and make a fast filament because each motor has this filament attached to it.
Speaker A:And this is what propels the cell.
Speaker A:The network that regulates this flagella motor is called chemotactyl network has been really, really well understood.
Speaker A:And one could play around genetically with different proteins in this network and really see that this is essentially a system of antennas and feedback loops, really interesting feedback loops from the point of view of engineering to get a very high sensitivity and good response.
Speaker A:And then this output that is mechanical in the form of a motor that generates torque.
Speaker A:So as I was playing around with the cytoskeletal protein, I noticed that the cells are swelling and expanding.
Speaker A:When I was exchanging the solution that they were in.
Speaker A:And this is because they're under pressure.
Speaker A:And I could nicely see these volume changes.
Speaker A:And pressure regulation is quite important for bacteria.
Speaker A:They really regulate their pressure.
Speaker A:In other cases this is great because on an individual cell I can see volume changes.
Speaker A:And if I measure this really, really accurately, I read and I see the network itself is known.
Speaker A:The proteins that are involved in regulation of this pressure are known.
Speaker A:So I took an analogy, I will be able to figure out exactly how this works because I can play around genetically with some of these proteins and the output is the volume, which I can measure very accurately.
Speaker A:Similar like this chemotactic network where you have a couple of proteins and the output is the flagella motor.
Speaker A:You play around with them, you figure out the feedback loops and you know exactly how bacteria is navigating the environment.
Speaker A:But it turned out that this other osmoregulatory network, the one that regulates the pressure of the cell, is coupled to pretty much everything else that the cell does.
Speaker A:It's coupled to the rest of the physiology versus the chemotagne network is quite orthogonal.
Speaker A:So when you're studying it, you're quite lucky because you play around with that network.
Speaker A:The rest of the cell is not touched much at all.
Speaker A:Versus where you play around with your smart network.
Speaker A:You, you mess everything.
Speaker A:You kind of, you, you have a bit of a.
Speaker A:What is a chicken and egg?
Speaker A:What is, what is the cause and what is the consequence?
Speaker A:So it's a lot more complex network than, than, than the one that I, I thought I was going to be working, you know, the one that we understand that I thought I was going to be working on something that's quite similar, but it was not at all.
Speaker B:That where you start in thinking, well that actually a lot of maybe like physics that we don't yet understand and we need to scratch a little bit, but the surface of that to find or not really.
Speaker A:No, that is precisely when I started thinking about it because it became quite obvious that you have one cell that is also an organism.
Speaker A:And that cell is regulating pressure, it's regulating swimming.
Speaker A:But the way that it's regulating pressure is linked to the way it's regulated swimming.
Speaker A:The way it's regulated swimming is linked to the way it generates energy and all of this.
Speaker A:And then it regulates certain intracellular concentration, like intracellular ph.
Speaker A:But that too is coupled to the energy generation, because energy generation is electrical as well.
Speaker A:So you kind of like realize that there is a lot of variables that are mathematically non trivially intertwined, but a cell does it.
Speaker A:And so the cell somehow maintains all of these homeostasis.
Speaker A:That became very interesting question, how does it do that?
Speaker A:And given how they're coupled mathematically coupled, these variables, how tight you can have these different homeostasis, maybe one variable, if you keep very, very tight, the others you can't, or something like that.
Speaker A:This became a really interesting problem in itself.
Speaker A:And I, to answer it, I combined the knowledge that I had when I was studying this rotary motors that are involved in energy generation with this pressure regulation that are ultimately coupled.
Speaker A:So it all kind of came together to look at what we're looking at now, which is like physiological variables and especially electrophysiological variables in a life of one cell.
Speaker A:It's for once, it's a bit more complicated than in multicellular organisms because there you have compartments, so you can say, okay, this compartment is, is going to be in charge from generating energy, and then the other compartment can use that similar type of energy as a signal, not necessarily just as an energy versus when you have one cell, everything is coupled together.
Speaker A:So in a way it's more complex.
Speaker A:So, yeah, that's kind of like it all came together to what we're working on now.
Speaker C:So by now you're fully specialized in biological physics.
Speaker C:And you mentioned to us that maybe over time, maybe, maybe if not after, after Princeton, as you're moving back to Edinburgh, the way people study the proteins in the cells kind of has changed and adapted, and we're now using different techniques to the ones that we used very early on in your research.
Speaker C:Could you explain a little bit more about in vivo versus in vitro and why these are different and why now people focus on a different version of these techniques to the ones they used in the past.
Speaker A:Right.
Speaker A:So this is actually maybe something I should have explained right at the beginning because the way people use in vivo is different depending on which field you're talking about in your field.
Speaker A:So in vitro is quite straightforward, right?
Speaker A:You take it out of the cell and you purify a protein and then you can maneuver it without the cell being just protein needs to be active.
Speaker A:In vivo for us is when a cell is alive in vivo for many could be in a whole living organism or in a mouse or another animal.
Speaker A:The in vivo is the one that gets mixed a little bit.
Speaker A:So for us, it means that the proteins are looked at when the cell, the bacterial cell is still alive.
Speaker A:I guess before, when this molecular motor field started, most of the proteins would be purified and then different ways applying forces would be used, like optical tweezers, which is A sharply focused laser beam that can apply force at the right scale so that these motors can be maneuvered in vitro.
Speaker A:But there is only so much one can do because you can purify them all and then you can, you know, push and pull and you get the information that you can from that.
Speaker A:But at some point you now need to start looking at how does this work inside the cell.
Speaker A:And then it becomes harder because the cell is influencing what you're looking as well.
Speaker A:So the imaging becomes harder, manipulating comes harder, but also understanding what it is that is happening becomes harder as well.
Speaker A:But people are tackling that as well.
Speaker C:And speaking about cells and their environments, you mentioned that when you're in Edinburgh, you were spinning out a company based on some of this work.
Speaker C:Could you tell us a little bit more about that work and that company?
Speaker A:Yeah.
Speaker A:So I would say that my lab is very much focused on very basic research.
Speaker A:But I learned that by communicating with industry, we can quite effectively translate what we do by answering basic level questions into the application.
Speaker A:And the key that I found was rather than me going to the industry and telling them what I do and expecting that they will understand, how is this relevant for them?
Speaker A:It worked a lot better when they would tell me what their problems were and then I would, oh, actually this thing that we've been looking at, we think that is going to be quite relevant for us because some of these osmotic shocks are used in biotechnology, for example, to get proteins out of the cell.
Speaker A:We can like almost burst them up.
Speaker A:You open them up.
Speaker A:So that works.
Speaker A:And that is encouraged me to work on the interface as well.
Speaker A:It went from working with industry to companies coming out of the lab.
Speaker A: t one was started in February: Speaker A:It came from long standing frustration that to grow bacterial cells the right stage where you need them to do the experiment, can be relatively antisocial.
Speaker A:Right.
Speaker A:They have a certain doubling time in certain media.
Speaker A:That doubling time is different.
Speaker A:So you may be waiting for 12 hours, you may be waiting for eight hours.
Speaker A:That is horrible.
Speaker A:Where you come in the morning and eight hours later you can only start the experiment.
Speaker A:And I wanted to buy both for myself and also for the lab, something that will automatically grow and keep them in the right state.
Speaker A:And this was not available unless you had to pay a lot.
Speaker A:So this is the where the company came in.
Speaker A:We're simply making these bioreactors at the volumes that we needed.
Speaker A:The lab which 10 to 20 milliliters which also turned out to be where bigger companies, industrial biotech companies.
Speaker A:There was nothing at that scale that was available as well.
Speaker A:So it was interesting to them as well.
Speaker A:There's a little bit of luck there.
Speaker A:Right.
Speaker A:We kind of like we were motivated by the scale that we use in the lab and it turned out that that scale scale was not covered by what was already available on the market.
Speaker A:So that the big biotech was also interested in the devices.
Speaker C:And you also mentioned biosensors to us earlier.
Speaker A:Indeed.
Speaker A:So there is another company that is right now looking for funding.
Speaker A:Right.
Speaker A:In the process of funding, I would say in the instance of the first one, which is called Oggy Biotech, I was certain that we can make the devices to high quality.
Speaker A:How many people would buy it outside of my own lab and the colleagues who are interested in it that I wasn't as certain at that.
Speaker A:That was a little bit of discovery process and there was an element of luck.
Speaker A:But with the other one I'm way more certain that people will want because the need to sense analytes in liquid is big.
Speaker A:All kinds of analytes including ions and metals.
Speaker A:But the technology is so challenging that I wasn't certain what is going to work.
Speaker A:Right.
Speaker A:So what we essentially doing, we're putting individual bacteria that are engineered to sense an analyte and this is relatively straightforward to do.
Speaker A:And the signal from the bacteria detecting an analyte is sent down to this bacterial flagella motor that is normally there to enable bacteria to swim.
Speaker A:And we put a marker on this motor so that the marker is marking the rotation of the motor.
Speaker A:And we position that into customized integrated circuit and micron sized electrodes.
Speaker A:So it's all literally happening at 1 millimeter square.
Speaker A:And there is bacteria right next to these electrodes getting electrons out straight from the circuit.
Speaker A:And then one can position thousands of these different cells and engineer them to send different analyze really, really quickly.
Speaker A:And the output is always, it's electrical, it's still electrons.
Speaker A:So it's very easy to integrate into the current into the current semiconductor based technology.
Speaker A:So yeah, this is the hope is that it will be used to sense many different analytes in the liquid.
Speaker A:But technology is really high.
Speaker A:We are positioning one bacteria next to one micro size electrode and it's an integrated circuit that is tiny but so far it's really, really going well.
Speaker A:So hopefully it'll keep on, keep on going in that direction.
Speaker C:Sounds fantastic.
Speaker C:And which, which companies do you think will find value in sensing these analyzes in water?
Speaker A:There are a Lot of different companies.
Speaker A:It was the challenge for the future CEO of the company was really distilling everyone who is interested in it to identify what are the beachhead markets, where to go first.
Speaker A:Because a lot of the people who were a lot of the industry that was interested, I'll tell you in a second who they are did not have the necessary technology to implement something like that, something as normal as that, the current processes.
Speaker A:So they need the company to do the packaging around it as well.
Speaker A:And we need to do this.
Speaker A:You really need to focus.
Speaker A:Okay, I can't do it for everyone because they have very different requirements.
Speaker A:I need to do it for a few beachhead markets.
Speaker A:Some of them is for remote sensing, but in principle you can send the sensor out, you can drop it into the field.
Speaker A:You don't need to have it in the lab because low power.
Speaker A:But we decided to focus.
Speaker A:The beachhead markets are offshore infrastructure.
Speaker A:That is the second one.
Speaker A:And the first one is really aquaculture is the fish again.
Speaker C:So after all this time, even though you didn't go to Dresden, you're working with fish.
Speaker A:Yes.
Speaker A:So indeed there's a lot of labs in the world that maintain fish for research and they need to be maintained quite well.
Speaker A:And also, you know, fish for consumption, like salmon and all of that and measuring the analyze in water to ensure the quality of fish, both for consumption but also for research purposes is something that is done in a very manual and painstaking way.
Speaker A:So they are really looking for improvements there.
Speaker A:Offshore infrastructure is an obvious one because it's quite hard to go out.
Speaker A:So something that is in situ and it's sending wireless information would be really, really valuable now.
Speaker B:You just recently moved to Cambridge and you moved your lab from.
Speaker B:Well, you took your lab with you.
Speaker B:Why move to a physics department after so much time in biology or bio related departments?
Speaker A:So I will say that I always view myself still as a physicist while being at the biological sciences department.
Speaker A:And I think the reason I moved back is that I was finding the topics that we are trying to answer are more suited for students who have a physics background.
Speaker A:And that balance there will always be about at least 40% of PhD students who were with physics background and postdocs in my lab.
Speaker A:But that balance was shifting a bit through the years and in recent couple of years it was going more into someone with a physics background more suited for the kind of questions we are asking.
Speaker A:Not all of them, but for majority of them.
Speaker A:And I thought that this is going to continue, it's just going to go more in that direction.
Speaker A:So that was one of the reasons why I decided to go back.
Speaker A:The one was probably is as a physicist in the biological sciences department in Edinburgh, for example.
Speaker A:It was a unique department in the sense that they hired many physicists, mathematicians, engineers within the department as well as collaborate with the departments, those departments.
Speaker A:And some of the vision was well, biology is becoming very quantitative science.
Speaker A:So let's get the expertise from chemists, physicists, mathematicians to help us shape that discipline so that it becomes its own heavily data, quantitative based discipline.
Speaker A:I subscribe to that vision but at the same time the kind of questions we are asking right now I view as that they hold genuinely new physics.
Speaker A:Not new physical forces, Right.
Speaker A:But new concepts that we haven't explained yet.
Speaker A:And I think that that is more suited for the physics department.
Speaker B:And so what is it about Cambridge and the caverns?
Speaker B:Is that like being surrounded by people that are from other field of research and specialties but within physics?
Speaker B:That was the, like the appeal of Cambridge in particular?
Speaker A:Indeed it was.
Speaker A:It was the fact that, you know, this is essentially a challenge when you're working on with living matter because you can't really, you can't really.
Speaker A:Well you can, but it is still challenging Life, living matter throws at you physics from all kinds of directions.
Speaker A:You can't decide I'm going to be an expert in this and this because you just don't know what is going to hit you, right?
Speaker A:There is elements from, you know, soft matter, then there is elements from non equilibrium thermodynamics, then there is something completely electrical where you know, you need to be handling or like you're building these devices integrated circuit that.
Speaker A:So I kind of felt like that this expertise in different areas of physics is precisely what I need to be able to learn fast enough and get the right collaborators to handle all of these problems that, that life is, life is throwing at you because it's quite unpredictable, it's quite challenging.
Speaker A:You want to be very careful that you don't know nothing about everything.
Speaker A:Right.
Speaker A:And you have little control because what kind of physics comes at you when you're looking at these systems?
Speaker A:They want to understand how living cell as a whole works.
Speaker A:It's, it's, it's out of your control in a way.
Speaker A:Right.
Speaker A:So.
Speaker A:And you don't know the system well enough yet to be able to predict.
Speaker A:So I kind of felt that this different physics sub disciplines and, and experts in it is precisely what could benefit the research.
Speaker B:So now let me ask you, do you have any biochemists in your lab to make sure that you're not missing.
Speaker A:Any behavior right now.
Speaker A:Not.
Speaker A:Maybe I need to fix that.
Speaker A:That's a good point.
Speaker A:Thank you for the suggestion.
Speaker C:It sounds like you knew you wanted to be a researcher ever since the moment you chose to study physics.
Speaker C:Why was it that this path was so appealing to you back then?
Speaker C:Where do you find satisfaction in your role?
Speaker C:And also, have you ever looked back and wish you'd done architecture?
Speaker A:Well, let me start with the last one first, because that's who needs.
Speaker A:The answer is no.
Speaker A:I still enjoy, you know, know, like, I can read the building plans better than someone who wasn't exposed to it.
Speaker A:But that is a quick answer.
Speaker A:It's no.
Speaker A:Now, like, about being a researcher and what brings joy.
Speaker A:I guess I'm going to come back to something that I mentioned before.
Speaker A:It's like an itch.
Speaker A:Like, certain problems that I wish to solve just bother me.
Speaker A:They come out of nowhere and for some reason I want to find the answer to them.
Speaker A:I can't forget them until I solve them.
Speaker A:And that is really what, for me, drives research.
Speaker A:Right.
Speaker A:It's literally, you feel like you need to scratch, and until you scratch it, you can't let go.
Speaker C:So it's that feeling that decides the question.
Speaker A:It's precisely.
Speaker A:It's like it's not rational and you rationally go about solving the problem.
Speaker A:But what I find that how I choose the problems is not a rational problem.
Speaker A:It's just something that.
Speaker A:Okay, this is something that I.
Speaker A:Not only I'm excited about it, I'm excited about many things that I don't necessarily wish to solve myself.
Speaker A:This is.
Speaker A:I'm excited about it and I do want to.
Speaker A:It bothers me.
Speaker A:I want to solve this.
Speaker C:And do you have any questions that you really want to solve, you haven't yet that you've left open?
Speaker A:Not only the ones that I left open, the ones that I haven't had the opportunity to touch.
Speaker A:It's just like.
Speaker A:It seems to be an enormous source of problems that I do want to solve.
Speaker A:And the ones that I haven't solved, they keep bothering me.
Speaker A:And I come back and I hope that I'm going to solve them.
Speaker A:And although they're probably going to be many open questions by the time I'm done with it as well.
Speaker A:So.
Speaker A:Yeah.
Speaker B:Do you keep track or are they.
Speaker A:Oh, I do keep.
Speaker A:They keep track from the.
Speaker A:By themselves.
Speaker A:They're kind of like lingering somewhere in the back of the mind, bothering me that they haven't still been solved.
Speaker B:So, yeah, we're gonna end There.
Speaker B:But you said before that in science nobody really knows all the answers and that this is okay.
Speaker B:You have to live with the fact that the best that you're going to do is an educated guess.
Speaker B:Would that be the advice that you would give?
Speaker B:Like, what would you say to young, inspiring scientists and in particular experimentalists that are thinking about going into this kind of career?
Speaker A:I would give this as an advice just to set the expectations.
Speaker A:Right.
Speaker A:Because if you're aware of it, I find that you're handling it.
Speaker A:You're not surprised by it.
Speaker A:It is the very nature of it.
Speaker A:But at the same time, what you find, that's the answer.
Speaker A:And the people that you're going to be interacting in order to answer that just takes you to places you would never go otherwise, and you can never predict where it's going to be.
Speaker A:It's that unpredictable.
Speaker A:And this is really.
Speaker A:This is.
Speaker A:This is really exciting.
Speaker A:Right?
Speaker A:This is really, I would say this element, you know, like, it's tedious sometimes.
Speaker A:Right.
Speaker A:It's a.
Speaker A:Many times you get stuck and enjoying and that.
Speaker A:That's part of the process.
Speaker A:And if it was easy, it would probably been answered before.
Speaker A:So getting stuck and getting, you know, and trying to disentangle yourself, that is something that is part of process as well.
Speaker A:And it's often there.
Speaker A:So I would also advise, I would mention this so just that everyone is aware that it's.
Speaker A:It's.
Speaker A:It's sometimes quite slow for a reason.
Speaker A:But I guess that getting stuck, I find motivational as well.
Speaker A:Right.
Speaker A:So kind of like, you know, okay, this way, that way, try this, try that, like, and try to get yourself unstuck.
Speaker A:Right?
Speaker A:That, that is like, if that.
Speaker A:If that is something that motivates a person, that is probably a.
Speaker A:Right, right career choice.
Speaker C:So it takes a bit of imagination, I guess.
Speaker A:Imagination, but also perseverance.
Speaker A:Perseverance, yeah, yeah, yeah, both.
Speaker B:And patience.
Speaker A:Patience.
Speaker A:Patience is quite.
Speaker A:Is quite important.
Speaker A:It's not necessarily a fast process.
Speaker A:Sometimes it is, but most of the time it's not a fast process.
Speaker A:It's definitely a marathon and a bit.
Speaker C:Of resilience as well.
Speaker A:Yeah, indeed.
Speaker A:There are plenty of awards, but, yeah, yeah, their resilience is important.
Speaker B:Excellent.
Speaker B:Thank you so much for being here today, today and for your time.
Speaker B:It was lovely.
Speaker A:Thank you for having me both.
Speaker C:Thank you to Pilazota for joining us today.
Speaker C:As always, if you would like to learn more about what we discussed in this episode and more generally about our work at Cavendish Laboratory, please have a look at the show notes or go to our website.
Speaker C:If you have any questions you would like to ask our physicists, head to social media and tag us with peopledoingphysics.
Speaker C:This episode was recorded and edited by Chris Brock.
Speaker C:Thank you for listening to people doing physics.
Speaker C:We'll be back next month.
