David Piston (WUSTL)

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Intro/Outro (00:00:02):
Welcome to The Microscopists, a Bitesize Bio podcast hosted by Peter O'Toole, sponsored by Zeiss Microscopy. Today on The Microscopists.

Peter O'Toole (00:00:14):
Today on The Microscopists, I'm joined by Dave Piston Professor and Head of Cell Biology and Physiology at the Washington University School of Medicine in St. Louis, Dave uses innovative imaging and biochemical methods to identify new therapeutic targets for diabetes, but microscopy and biology was definitely not where he started. And

David Piston (00:00:36):
Yeah, as Ultrafast laser physics was sort of where I was that's. That was my first love.

Peter O'Toole (00:00:41):
That was until his early passion in physics became much less interesting to him.

David Piston (00:00:45):
In fact, I think I probably wanted to do that up until the time I was in graduate school and realized he had to take two years of quantum mechanics. I took a year of quantum mechanics and I somehow got an A on the course, but I didn't understand the make up of it.

Peter O'Toole (00:00:56):
And we discuss his recent exploit in Singapore, where he was able to combine his love for travel and science

David Piston (00:01:03):
It's. I like going over there it's it's you know, you don't, it is 12 hours time difference, so you don't get jet lagged. It's just complete sleep deprivation.

Peter O'Toole (00:01:11):
And we hear about the role serendipity has played in his career so far,

David Piston (00:01:16):
Right place, right time. I guess I started doing that and I realized there's a lot of interesting biology that can be done once you have the ability to do site directed mutants

Peter O'Toole (00:01:26):
All in this episode of The Microscopists. Hi, I'm Peter O'Toole from the University of York and today I'm joined by Dave Piston for the Washington School of Medicine. Dave, how are you today?

David Piston (00:01:44):
Doing great.

Peter O'Toole (00:01:46):
God, that's the hardest bit done. Dave, I I've known of you for many, many years, my PhD days. But I met you, I think, oh gosh, I can't remember if it was in Gent or if it was in Munich or Heidelberg somewhere.

David Piston (00:02:03):
I think it was in Munich

Peter O'Toole (00:02:04):
Now. So that was a, I think a workshop on collerated microscopy and workflow. Yeah.

David Piston (00:02:10):

Peter O'Toole (00:02:12):
But interestingly, I know you for your, your biochem, From my side, I'd say more biochemistry biophysics side, but your background is in physics, is that correct?

David Piston (00:02:21):
Yeah. As Ultrafast laser physics was sort of where I was that's that was my first love.

Peter O'Toole (00:02:27):
So, so what happens to your first love if it's not any, what, who's your second love then if you've got a first love of ultra?

David Piston (00:02:34):
Well, I mean so I was, you know, working in Ultrafast lasers and doing spectroscopy and at the time when I was sort of in graduate school was sort of the end of the cold war and funding for a lot of solid state physics especially Mesoscopic and, and single towards single molecule type of solid state physics was, had not really developed, was drying up. Cause a lot of it had been defense related funding, I think. And and so also there was just sort of a dearth of new, interesting problems, high, high TC, super conductivity hadn't come around yet. A lot of the interesting Mesoscopic things like graphing and different special materials sort of hadn't hadn't really been developed. And when I was working, it was I was in graduate school. I was T TAing for a guy named Enrico Gratton, who ended up being my PhD advisor and he was using laser spectroscopy, but putting biomolecules in the [inaudible] rather than solid state stuff. And he needed somebody that could run the lasers and develop some new ultra high frequency parallel harmonic content analysis tools. And these are the sort of things I liked doing. So he had money at the time and I joined his lab and, and I started doing you know, sort of getting a little bit into biophysics that way. And then you know, I, I sort of had decided I wanted to learn something about imaging and because there was, it was the idea of doing parallel spectroscopy, where instead of doing just one spot of spectroscopy, you can do, do everything in sort of in parallel. And I thought, well, you could do imaging really fast. And with sort of things like con focal, you could start doing things like fluorescence correlation, spectroscopy, a lot of very interesting analysis techniques that you could use then. And, and so I went to Watt Webb's lab at Cornell, and as I showed up, there was just when two photon was invented by Winfried Denk and Jim Strickler and, and Webb. And they needed somebody that knew something about ultra fast lasers photon to second lasers to push the two photon technology forward. So right place, right time, I guess I started doing that and I realized there's a lot of interesting biology that can be done once you have the ability to do site directed mutants. So site directed mutants genesis of proteins was invented while I was in graduate school and so it was sort of new and you then could, you could take an enzyme and you could make different mutations to it. And you could say, make it less active, more active, a little more active inactive, then you could get an access, you could plot data, and if you can have an access and plot data, physicists can try to figure it out. So so I sort I'd go down that road and I just slowly and surely went more and more biological mainly because that's where the, where my interests lay. I mean, there were interesting problems to work on and we started pursuing them. And now I think I'm not much of a physicist anymore. Now my, my second love is pancreatic eyelet

Peter O'Toole (00:05:44):
. So I, I think that that's really enlightening sort of track, you know, you, you've gone from kind of a hardcore physicist now into a, a hardcore physiologist biologist, biochemist biophysicist, whichever way you want to word it through that at the age of 10, where do you, so, so as a young child where, what did you see your future career to be

David Piston (00:06:08):
When I was 10? Well, it's, I don't know if you read this someplace when I was 10, I made my first telescope

Peter O'Toole (00:06:13):

David Piston (00:06:14):
At that time, yeah, I ground a six inch reflecting neon reflector mirror the local local amateur astronomy group had this grind, your own mirror, build your own telescope workshop. And I went and grounded my own mirror and built a telescope out of eight inch tube and the little wooden Mount and a few parts that you had to buy from Edmond scientific and and built that. And I thought, I always thought I would be an astrophysicist. I thought that was that's really what I wanted to do. In fact, I think I probably wanted to do that up until the time I was in graduate school and realized you had to take two years of quantum mechanics. I took, I took a year of quantum mechanics and I somehow got an A in the course, but I didn't understand the make up of it. I mean, I, I know how to do the problems. I'm a good enough mathematician to do the problems. And I, I kind of get the concept that I like things. So I have some intuition about 'em right. I can, I can, I like things where you can do something to say, here's a simple version is my theory. Right. And in quantum mechanics, it's, there's no such thing.

Peter O'Toole (00:07:18):
So, so, so, so you, I guess that's where your pa passion triggered off, you got into physics, you realized that astrophysics wasn't for you.

David Piston (00:07:26):

Peter O'Toole (00:07:27):
So at that age, where did you see yourself going? Cause it certainly wasn't in the bio. It was hard

David Piston (00:07:31):
If he, oh, no, it wasn't in the bio. It was really, really in, I, I was, I really wanted to do I was really interested in maybe doing single mole. What, what does a single molecule look like at a in a, in a transistor the idea being that when you have transistors, you know, a lot of the, the pn junction, a lot of the theory is, is bulk, but they're making these things smaller and smaller and smaller so that you have a hundred charge carriers or, or fewer. And when you, when you get to that level, now you're no longer, you're really not in a statistical regime anymore. You start to get into more of a single molecule regime. So trying to look at axis on whole recombination or those sort of things, right at a, at a, at a material junction where you can get to sort of single events. And then, you know, is it possible to build a transistor that would be, I guess in sense, be like a quantum transistor in a sense now where they're talking about quantum computing, where, where you're really looking at single, single quantal events to store data or to, to process data. So I sort of wanted to do that, but the labs that we're doing that sort of spectroscopy didn't, they were having trouble fund getting funding. They, the, the students there had to TA a lot. And so it seemed, seemed to me, I, I, I liked working in the lab. I I'm sort of a, for better term lab rat, you know, I, I like, I like going and turning the lights out and, and giving a Allen wrench in one hand and a mirror adjustment in the other hand and building my own lasers and these sort of things. That's what I like doing. So

Peter O'Toole (00:09:07):
Tell me, you're not still doing that.

David Piston (00:09:11):
Doesn't I have a microscope back here. I, but no, I, I I, I, they don't let me pass that door. My lab is through that door back there and they, they usually don't like me to come back there. Every once in a while I'll go, I'll go help you know, put together a, a new floating table you know, optical table and get the floating balanced of the legs or something like that. But the lasers now lasers, we buy now are completely sealed cavities, and they don't, there's no user serviceable parts. They, they dial into it by the internet and if they can't fix it, they send you a new one and they come and put that on the, and take your old one and put it in the box and send it back, it'll tell you a story. When coherent had the first sealed cavity, Ty Sapphire we had one and it wasn't working. I thought, well, let's just take the top off and see if there's anything we can do. And I think there was something on the order of 320 allen wrench allen screws on it. And, and I was looking at this, I said, 320. I don't think I can undo all those before their service. Guy's gonna show up. When I talked to, when I talked to the designers, they said, yeah, I'm sure there was a meeting someplace where, where they said, how many, how many screws do we have to put on before Piston will try to open it? You know, they, so I said, 50, oh no, no, he'll open 50. So they got to 320 or something. They said, yeah, that's probably enough.

Peter O'Toole (00:10:32):
it worked?

David Piston (00:10:34):
Yeah, me, no, I haven't. I, I haven't I haven't worked in my own lab in a long time. I've taken a couple sabbaticals and have worked in the lab over the summers in 2011 at Woods hole and then in 2019 in at Astar in Singapore.

Peter O'Toole (00:10:50):
Oh. So, so you sent me a picture of,

David Piston (00:10:53):
Yeah, there's me. That's, that's me. I'm mixing up a buffer. I know. I look really like, I'm really professional there. All I'm doing is making up, making up a buffer from my experiments, but I did some did some experiments with looking at acton and calcium in polymerization and calcium in the, in beta cells and alpha cells got some preliminary data for a grant that we've since gotten funded. And I have a, a postdoc now that's working on that project, taking it forward. So

Peter O'Toole (00:11:18):
I, I think the scariest thing is, is the thoughts are a physicist with a, with Eppendorf Gilson pipetting in the hand.

David Piston (00:11:26):
Well, I look like I know what I'm doing, don't I,

Peter O'Toole (00:11:28):
It looks very convincing. Yeah. Well, I'm sure politicians do that. When they go into care science labs,

David Piston (00:11:34):
I was just making up a buffer. I think, I think somebody else had to take out my hand to at folks. I couldn't get the PH meter to work in their lab.

Peter O'Toole (00:11:43):
So, so how long were you over for an Astar for?

David Piston (00:11:46):
So we were the, we, I was there. I was in the lab for eight weeks.

Peter O'Toole (00:11:52):
How'd you enjoy? Astar Singapore.

David Piston (00:11:54):
Oh, I like, I like I like going there a lot. It's I've been there quite a bit. I started to go in there as a collaborator for Britton Chance about 12, 13 years ago. I guess I've been working with Wade Ping Han there in the, in the imaging imaging consortium. It's I like going over there it's it's you know, you don't, it's 12 hours time, distance, so you don't get jet lagged. It's just complete sleep deprivation. but they have a large group that works on eyelets and it also does cancer stuff and they do a lot of high end imaging in the areas where that I work. And so it's it's good. It's a place to, you know, it's it's as a, as a, you know, so a national lab, it just, people there are working and they, they have equipment that works and it's there's nothing bubblegum and you know, together. So it's a place you can go and just, just I had a little office little bench and a microscope and that's all I need.

Peter O'Toole (00:12:59):
All sounds cool. So thinking about that side, so obviously we've talked about how your careers progressed through to it, but you also head of the department cell biology and physiology, which again is a very different job description compared to running your own lab. Yeah. When you start to become head of a department. So what have been the biggest challenges for you in that, in the, in the role of head of the department?

David Piston (00:13:24):
Yeah, so I guess the, the biggest challenge is, is the biggest challenge is always communicating with people and keeping them on the, you know, keeping them on the same track and keeping them, knowing what you're doing. If you start doing things, it gets people together and they say, yeah, let's do this. And then you start doing it. If you don't report back to them, then they think you aren't doing it, or they think you're doing it wrong. Even if you are doing what they want. So that's probably against my nature a little bit. I just, yeah, we have this agreement now I'm doing my part. I'm gonna I'll report when I'm done. So that's, that's sort of been for me, particularly a tougher part of it. I think that the obviously managing department through COVID has been a tough part and then the communication was even more important, but the communication was so important then that it had to be done. Yeah. Right. I mean, I was the, I was the lifeline for all the communication from the, from the administration about what was allowed, what wasn't allowed, how we could keep things going. So it really forced me to communicate that's that was my full time job really was just communicating up and back and, and side to side, peer to peer with the Dean's office, to my faculty, with my other chair colleagues across the campus, from the medical school to the arts and science and engineering campuses that were struggling with the same sort of thing. So you know, I think that, that taught me a lot about how to be more efficient with that. But that's certainly, you know, that's not something that I'm, I'm good at signing things and, and doing the budget and things like that. I, it just, I've always sort of had a knack for, for budgets and numbers. And so that was that just something a lot of chairs really struggle with. And for me, that wasn't hard. But there's a lot of people that are much more natural communicators and keep people up to date with what they're doing all the time and that's not my natural style. So that was that's, that's been the hardest, that's the hardest thing, right? People don't trust people don't trust you. It's like, why wouldn't you trust me? I'm the most trustworthy guy there is, but, you know, until they've seen it over and over and over, they don't, they don't know. So

Peter O'Toole (00:15:38):
Yeah. And people, you, you always get new people as well. So, so that, that, that knowledge goes,

David Piston (00:15:43):
Yeah, no, That's right.

Peter O'Toole (00:15:44):
Fresh faces and, and you're right. Why, you know, why would they know that at the start? So what, what would you say your management style is?

David Piston (00:15:54):
Well, I mean in general, it's, I'm very hands off. I'm very [inaudible]. I mean, I try to hire people that are good and get out of their way. you know, if, if I've hired people that aren't good, I've had to work pretty hard to convince them that they need to be someplace else. I'm, not going to micro manage them and help them all the time.

Peter O'Toole (00:16:17):
How hard a gig is that though, when they, when they're underperforming, how do you get to try and either perform? Can you ever get 'em to perform ultimately?

David Piston (00:16:27):
Yeah. no, generally I control their salaries and people don't like pay cuts

Peter O'Toole (00:16:36):
That must be a hard gig as well saying, sorry, X, but you've

David Piston (00:16:42):
Well, I mean, you have to document, you have to document it. And we have enough, enough management things in place where with the staff there have to be annual evaluations and we have good support from HR for you know, for helping people with performance improvement, counseling and, and what not. Now that's, you know, for the professional staff for the, for the hourly workers, you know, my lab in, in my lab, I've had several people that come in that have ended up with master's degrees. I think they were every bit capable of doing a PhD. I think they needed a person that was gonna be a lot more hands on to, to help them. In fact, one, one case we got the person into another PhD program. He actually was just in the wrong PhD program for him. Yeah. So went back to more material science finished did is doing great. And so I think, you know, I'm pretty, I'm pretty open with people when they come to my lab. This is how I am, and this is, I expect you to be fully self-motivated. And I will, my job is to help you succeed, your job is to succeed. Right. I mean, I, I like, I can't do that for you.

Peter O'Toole (00:17:59):
Yeah. I, I, yeah, full credit. I think it's a really difficult gig. Cause I can imagine you will take the department in a direction and not everyone will want to go in that direction necessarily. And yeah. You know, we're talking very senior staff in some of these cases, so how do you get them to follow or do you just go and that's the way it is?

David Piston (00:18:18):
Well, that's the way it is. I mean, it's, at some point that's the way it is. Yeah. It's yeah. I mean, there's people that wanna change things is people that want more support and more they think, oh, we should, you should be doing more of this or more of that. I said, well, that's not, yeah. We, we talk as a faculty we've we had our five year department review. It was actually at six years because it was supposed to happen right before COVID, you know, right as COVID was starting, got delayed. And we've had a sort of a external, external visitors come and see the department and interview everybody. And we've sat down as a faculty and made some strategic plans. They're not really so strategic as much as their organizational and tactical, but the idea is what we want to do. And I've, I've let the faculty lead a lot of those different different things. And some of them go better than others. And, and I think they realize how much work it is to actually make some of these things come, come to, to fruition.

Peter O'Toole (00:19:23):
So, so, so we've, we've gone right through the cycle of wanting to be an astrophysicist, realizing that wasn't for you to become a physicist, to realizing the opportunities were maybe more limited by the single particle materials and moving into the life scientists to quite which you've still kept obviously, but also taken on this other responsibility. Give it another 10 years. What would your ideal job be? If you could do any job in the world, what would it be?

David Piston (00:19:49):
Well, so I don't know what, I don't know what it's gonna be like then, but I tell you if I was retiring. So I, I, I plan to close my lab in about 10 to 12 years. A, I think science is a young person's game. And I think that there's too many people that are over 65 that have huge amounts of NIH funding, which is why young people can't get started very easily. So but I, I don't plan on, I close my lab and I'll retire from doing active science, but I, I guess I have an idea of writing maybe writing a textbook or two if there's still a need for them, there really is a need right now for, for a serious microscopy booked. That would be a little kind of like the, the, the pre, the successor of the video microscopy book of Shinya Inoue. Um there's a lot of stuff in there that's really very, very valuable, but there a lot of things now with how we do analysis and how things are totally digital seamless that really needs to be integrated into that. So that would be something I might wanna do. And then the other thing I wanna do is write webpages for nonprofits. Cause I there's like some nonprofit or agency that I hear of and I want to give them some money and I go to their webpage. I can't figure out how to donate and I'm not gonna pick up a chequebook and write it, cheque and stick it in an envelope. I just don't. I a, I don't know if I have an envelope so I think that I want these people to join the 21st century. So there's, there's a couple of companies that have started, you know, hosting a lot of nonprofits and giving tools, but those, those poor company, you know, those, those people are out there helping, helping homeless people and helping hungry people and they need to be out doing that, not writing webpages. So I think I'd like to do something like that for a second career.

Peter O'Toole (00:21:45):
Ah, that's a pretty cool

David Piston (00:21:47):
Maybe just to get, maybe to get my programming skills back cuz you know, my, I taught my daughter's Java programming, so, and so I was realizing how much I missed doing that sort of stuff.

Peter O'Toole (00:22:02):
So, so going through, obviously there's been quite stressful times in the lab. What do you do outside of the lab to chill out?

David Piston (00:22:11):
Oh, so so I mean now I have a couple of girls in high school, so that's most of what I do is try to figure out where they are whether, whether they need a ride or a car or something. My older daughter's driving now. So is

Peter O'Toole (00:22:24):
This your family?

David Piston (00:22:25):
Oh, this is that's that's my family. Yeah. That's okay. Yeah. So when we went to, so the reason, one of the reasons to go to Singapore and Astar was that I wanted to get my family out of the country and my daughters at that time, I think we're probably 12 and 12 and 10. Something like that, 13 and 13 and 11. And so Singapore, they speak English, right? So, and all the signs are in English, even if they people speak Chinese or, or Indian or maylay all the signs are in English and you can, you can get around in English. And so we, we got a chance to go to angkor wat. This is us at, at angkor wat, which was one of my bucket lists places. That's my wife there in the paint on the, on the, on the right, I guess. Yep. and and obviously the old bald guys, me and my older daughter, Casey is on the right. And then Elena is the one is on the left. So we had, we had a blast in, in at angkor wat and that so that's, that's yeah, we, I mean, we like to travel, I like to travel. We don't, we don't get to travel as much as we used to. We go to Florida for a couple of weeks for vacation and go to the beach. And the girls are both having friends down this year to, to stay in the house with us. So we'll see how, we'll see how that goes.

Peter O'Toole (00:23:51):
Are they following in your footsteps with the way of physics or life science?

David Piston (00:23:55):
No, not at all. I think as far as possible my, my older daughter's much more of a English I English. I think she probably wants to do writing, although she's thinking about maybe being a doctor now. So I think that has more to do with her friends. Mom is a pediatrician than, than anything else, but she's thinking about maybe doing premed. So the younger one is she's very, she's very into math and science, but I don't think she wants to be a professional scientist at all. I don't know if she's thought much about what she she's really into writing. She does a lot of creative writing and writes stories and doing a lot of reading. So

Peter O'Toole (00:24:34):
, I was just thinking the irony of a scientist who's got creative writing is quite dangerous recipe.

David Piston (00:24:39):
Yes, that's right. Well, hopefully we don't have very much creative writing in my, in my, in my business.

Peter O'Toole (00:24:44):
see over that

David Piston (00:24:46):
We read, we read a little bit of it when we're reviewing articles, occasionally,

Peter O'Toole (00:24:51):
You, you sent a picture of a, of this as well, but no, you caught.

David Piston (00:24:57):
Yeah. That's a, that's a 36 pound stripe bass I thought off of woods hole. So that's the other thing is that so this is actually represents my teaching. So, you know, for many years I taught at Woods Hole and at Mount Holyoke, biological lab, the microscopy courses, I taught both AQLM and and OMIBS at Woods Hole and then the spring and fall courses. And then I taught with Simon Watkins. This course, we started up in in Maine at, at the in the aflred for, for 20 years. I figured 20 years was long enough for, for me to do it. But this is, yeah, we went out, we went out early in the morning, just a little small open boat in October. It was miserable weather, but my friends say, if it's not miserable weather, you're never gonna catch something like this

Peter O'Toole (00:25:44):
For, for anyone who's not familiar with Woods Hole courses, go on, give a quick description.

David Piston (00:25:49):
Oh, so so the Marine biological lab at Woods Hole is one of the old Marine labs. If you're in England, you know, the MBA probably in Plymouth it's, it's pretty much patterned after the MBA Plymouth. And it was another place where they got squids and the squid giant Exxon were there. And people came from all over the world to do patch recordings on them there when they were running a lot of embryology that was done with sea urchins and sea stars and other things. This was day and age before FedEx, you couldn't get things sent to your lab. You had to go to, to where the to where the samples were. And Woods Hole has this huge summer program where they teach a physiology course and a neurobiology course that are sort of world famous. But they also have these specialized courses. And I have the microscopy course. So being a, been a big microscopy place over the years, Bob Allen and, and Shinya Inoue, both taught courses there. And Shinya was there for many, many years sort of the head of the imaging. And so it's like 20, 30 people come and it's 10 days or eight days, or I'm not sure how it used to be 10 days. I think it's down to like eight days now of of science camp. And you basically start at eight in the morning and go till 10 at night and lectures in the morning and the labs in the afternoon lecture, sort of the lectures late afternoon, and then labs again in the evening. And then eventually you go home and sleep some more

Peter O'Toole (00:27:18):
Dave thinking about the Inoue book, the video mic was video microscopy. Wasn't it was it video microscopy,

David Piston (00:27:25):
Yeah. Video microscopy,

Peter O'Toole (00:27:27):
Which, which was kind of a Bible. And it was one of a kind you said, you know, when you retire maybe writing or updating or a similar book, do you think that in today's age? Not, not textually, not, not as hard back, but do you think that, do you think the field has now got so big?

David Piston (00:27:43):
Oh yeah. It, it certainly wouldn't be encyclopedic the way it was when it was first written, but even the second version of it that he did with Ken Spring the second edition was not as encyclopedic. It had more at the end of quantitative stuff, but I think what, what, what is not ha is really quantitation, right? So what we, what we do now is we don't take pictures anymore. We're taking data. If you're, if you're using a confocal or a, or a, or a CCD or a seamless camera, you're taking data now, you might not be taking data because you're not paying attention. So you're just taking pictures, but you have the capability of taking data with very little, with very little extra work, but you have to understand what you're doing and you have to understand. And so, so just setting up a microscope to be quantitative, I think, is, is what you would wanna do. And then talk about how to care for that data to not screw it up. I mean, basically what comes outta the microscope is the best you can ever get. Right? You can only make it worse after that. Right. What comes out of the objective lens is the best you can get and everything else just makes it worse. So the trick is to talk about how to make it as little worse as possible. And so I think that it really, it's more about how to do microscopy in a way that teaches people how to do microscopy, not every kind of microscopy you could ever do. And there's a lot of books that have that, right. There's a lightsheet book about all these different ways to do lightsheet. And, and there was a lightsheet conference that we Abhishek Kumar and Gary Laevsky just had at Woods Hole. I was back at Woods Hole for the first time since I, well, not since I got that fish, but for, for 10 years this year, and not much changes on Cape Cod, I'll tell you that. But anyway, it was, you know, there was a guy who gave a, I don't remember who it was, but they gave a talk and they had all of the abbreviations they'd found in the literature. It filled up a whole slide of abbreviations for lightsheet microscopy different things. Right. And so you don't wanna be that way. I mean, the point is lightsheet gives you a way to take data that is three dimensionally resolved. So does confocal, right? So does turf to me, turf Confocal, lightsheet are all identical, right? There's a little bit about, there's a little bit about what the spread is and the thickness and these things, but those are all subtleties, right? I mean, that's, the data comes out in some sort that you get some sort of line of data that has some signal to background that has some signal to noise, and you can deal with that. Right. And those are the same, right. What comes out of an image is the same. And so what resolution is within that is something that can be well defined, but people think of resolution as being oh, the, the light, sheet's two microns thick, but that's not your resolution. Right. And the number of times I read that resolution is different and confocal than a widefield which is just not true. Most of the time, if people use a one area unit pinhole or bigger, the resolution's the same, the 3d discrimination is much, much different.

Peter O'Toole (00:30:50):
Yeah. Cause it, that focus so you can achieve.

David Piston (00:30:53):
Yeah. But resolution means something, right. You can't just, so I, I think just teaching people that these words mean something and what they mean and why, why they mean that. And, and what that means for what information you can gather in your image initially, and keep in your image as you're processing it through is important.

Peter O'Toole (00:31:10):
So thinking about imaging data and imaging data is big. You know, it, it is by definition. Yes. Big data. And, and depending on which modality you use, the data size is proportional to it. How do you see not just getting quantitative and preserving the data, how do you see the complexity of data analysis and getting the most out of that data moving in the, in the

David Piston (00:31:33):
Future? Yeah. So this is one thing that we've been talking about. We have a grant from the Beckman foundation on lightsheet microscopy, which is mainly to figure out these sort of things. And so there's obviously things you can do with compression, with lossless compression, but none of that really gets you very far. We have our, we have a dual view lightsheet with big cameras. We're using for spec hyperspectral imaging. And with that we can do about, I think it's 2.8 gigabytes a second. And so we can easily do 10 terabytes in a single experiment. This no way, it, it, I mean, you just can't do anything other than take that 10 terabyte disc and hold it in your hand and move it around to places, right. The internet isn't fast enough, nor will it ever no, will it be fast enough? But what we, what we have is we have a lot of data that is useless in there, right? We might be finding, we might be tracking particles. We might be checking cells, but we have all the area around ourselves in plaque. We have all the area, the cells that aren't there. So we need to figure out ways to reduce those data sets only to the cell we're looking at in real time because just, you know, you might wanna keep those 10 terabyte discs around forever, but you're never gonna be able to analyze it, get it, move it around and deal with it. Even using things like highly efficient programming languages, like Julia that are all real time and they don't load everything into Ram. And they, they do memory swapping without you knowing it and allow you to, to work. And apparently in real time on big data sets, but, you know, 10 terabytes is still too big of a data set. And so you wanna do things that are correlations across time and correlations across space, but you need to just throw away all the data that isn't there. Right? So if you're, if you have 16 bits, every place you have, or 32 bits, every place you have dark black, you know, sure. There's some fluctuations there, but you don't care. It's not tied to cell. So, so we have, you know, there's a lot of things you can do that just shrink the dataset into 20%, just easily, just by throwing away data. You don't have that isn't data and mapping things. And so there's a lot of idea about doing holographic maps. Yep. So you can, you can reduce things with holographic maps, into lossless data sets that keep all the information and they keep the data information in really deep you know, really deep bit numbers that reflect larger data sets. Uh and so tho those sort of things I think we're gonna have to do in order to move forward with this, right. So if we can take that 10, 10 terabytes and shrink it down into a couple hundred megabyte, a couple hundred gigabytes, well, then we can move it around on the internet that we have. Now we can process it on the GPU clusters that we have sitting on our desk and we can start to visualize it. We need to visualize it in real time. I mean, machine learning can visualize it in real time and track particles and do what, but we still have to look at it ourselves and see things that we aren't even asking the machine to see.

Peter O'Toole (00:34:40):
Yeah, no, absolutely. Would you say, I, I'm just thinking now and going back to when I started imaging with a liquid nitrogen chilled CCD camera, which I'm sure you remember those days and pouring it, chilling it and yeah. The final size were minimal, but massive compared to what we had, do you think it's now more difficult to get into microscopy than it was back 20 years ago or so think it's more, I, I dunno the answer.

David Piston (00:35:11):
No, it's actually, it's much easier. I think, I mean, I think you can buy, you can buy a high end for a hundred thousand dollars. You can buy a pretty high end microscope and and you can have high enough high enough end stuff to really get yourself in trouble. I mean, you can, you can cap capture all kinds of things. And I mean, I, I see people are basically just capturing noise. They're so sensitive. Right. And they're just capturing noise and they're just amplifying heck out of it. And

Peter O'Toole (00:35:42):
Yeah, so maybe that's more the point. Maybe it's maybe we, I, I, we were never asking simple questions. You know, we were pushing the limits of where it could go, but maybe we couldn't get into so much trouble because it wasn't turnkey.

David Piston (00:35:54):
It wasn't turnkey. So the only people that went there were people that knew you had to know what you were doing to, to do it. You had to invest the time. Right. If you were gonna invest the time in it's like electron microscopy in the old days, when you had to line the column yourself and do everything. I mean, there was nobody that couldn't look at an EM instantly and know whether it was good or not, you know, look, just look at the one picture and say, oh, this, this sample's no good. It's like, how can you, you know, how can you tell it's like, they just knew, right? I mean, I can go in and say, oh, this is outta focus. I couldn't even tell you which direction is outta focus. And the person's like, I couldn't figure get it in focus. Like, what do you, you're going the wrong way. Well, how do you know that? It's

Peter O'Toole (00:36:34):
How it looks now,

David Piston (00:36:35):
When you see it broken in enough times you learn this, right. But now they're not break. They have like perfect focus and they auto focus themselves. And the one time they don't, you don't know what to do. Right.

Peter O'Toole (00:36:46):
Don't actually one meeting this week had a data set and we look to where then, then the bombard question, this just doesn't look right. or whatever's gone wrong. Something's gone wrong somewhere. Doesn't look right. And so you analyze the microscope and then they say, no, it can't be the microscope. Cause, look at my previous image on five minutes before it, which was good.

David Piston (00:37:04):

Peter O'Toole (00:37:06):
So what's happened with the sample then it's got to be, that's just, yeah. It's just that level of engagement. And I think if you're right, you're generating lots of data and their images, but people need to look at both. Yeah. They need to set the data

David Piston (00:37:21):
And then they don't. Yeah. So they, they take their cells and they, whatever. They've made a transgen animal with a GFP in it. And they, they bring it down to the, to the microscope core and they pay $50 an hour to use some sort of high end microscope and everything. And then they go back and they try to analyze it on their, on their laptop with no memory and no, no computing power. And they, they won't invest in that,

Peter O'Toole (00:37:47):
Out of work. For me, it will come back to, so I've got some key questions I really want to get a feel for, but I'm gonna ask some quickfire questions first. So PC or Mac

David Piston (00:37:58):
PC. Not, not, not anything. It's just that all the instruments are controlled by PCs and it's

Peter O'Toole (00:38:05):
Mcdonald's or burger king

David Piston (00:38:06):

Peter O'Toole (00:38:08):
Oh, so what's your takeaway choice?

David Piston (00:38:11):
I cook at home. If that's stuff I have to do something like that. Ah,

Peter O'Toole (00:38:14):
So would you prefer to cook or wash up?

David Piston (00:38:17):
Oh, I both. Actually. I, I do both. All of I, I, I, I cook, I do all the cooking at home and and I wash the pan because I can't stand anyone else washing my pants.

Peter O'Toole (00:38:29):
Ah, so it's interesting. You wash your pants, but of everything else that goes in a dishwasher.

David Piston (00:38:32):
Yeah. Or, or if somebody else takes care of it. Yeah.

Peter O'Toole (00:38:34):
Yeah. But you can stay at the dishwasher because they're the pans.

David Piston (00:38:38):
Well, that's correct. Sometimes I have to rescue them from a dishwasher bit.

Peter O'Toole (00:38:41):
taking, these are more frying pans than just pots.

David Piston (00:38:46):
Just everything. Yeah. but mostly fry mostly. I mean, I, I have cast iron and, and and some stain, some, so stainless steel ones, and

Peter O'Toole (00:38:55):
I've never asked anyone this, how many frying pans do you have?

David Piston (00:38:59):
Oh well that, I used three, I guess.

Peter O'Toole (00:39:04):
Oh, I beat you on that one. gosh, there, we got more, but it scales up. We,

David Piston (00:39:10):
I have a lot, I have a lot, but I just don't use, I have a, I have a crepe pan. I just don't. I make crepes once a year. So I wouldn't say I use it.

Peter O'Toole (00:39:19):
Yeah. I think I've probably got about seven, but there's there's three or four hardcore ones that are used.

David Piston (00:39:24):

Peter O'Toole (00:39:25):
For, for, for very specific items or volume. Yeah. Big family. So grows up. Yeah. Tea or coffee.

David Piston (00:39:32):
Oh, coffee,

Peter O'Toole (00:39:34):
Wine or beer?

David Piston (00:39:36):

Peter O'Toole (00:39:38):
Chocolate or cheese.

David Piston (00:39:41):
Well, I guess ch it depends on what it depends on what . Those are two depends on which chocolate and which cheese, but I'll say cheese.

Peter O'Toole (00:39:50):
Okay. So you're a dark chocolate lover or a milk chocolate lover.

David Piston (00:39:54):
No more dark,

Peter O'Toole (00:39:55):
More dark. And I didn't ask actually, what's your coffee choice? Is it Americano? Is it Milky? Is it espressos?

Peter O'Toole (00:40:03):
You've got a big mug list.

David Piston (00:40:04):
Yeah. Well, it's a, actually I drink espresso, but if I drink espresso, I'd have like 50 of them. Cause I'm kind a volume guy. So generally, generally it's a watered down espresso.

Peter O'Toole (00:40:16):
You should never water down an espresso. That was no,

David Piston (00:40:18):
It's a, it's just a very long, let's just put it this way. It's a very long,

Peter O'Toole (00:40:22):
fair enough. Early bird or night owl.

David Piston (00:40:26):
I'm more of a night owl, but I, my job is more of an early bird job.

Peter O'Toole (00:40:30):
Okay. And what's your food heaven? What, what, what's your favorite food type?

David Piston (00:40:35):
My favorite food type. Well, I mean, I'm, I'm Italian by, by genetics. So I'd say Italian.

Peter O'Toole (00:40:42):
Okay. And what about your least favorite? If you, if you to go to a conference or someones take you out for dinner, when you, you invited speaker, they taking you back for dinner and it's a set menu. What is your dread that they're gonna put in front of you?

David Piston (00:40:54):
Oh lima beans.

Peter O'Toole (00:40:57):
That's a different one.

David Piston (00:41:02):
Like I like all food. I pretty much like all

Peter O'Toole (00:41:07):
Habits. Do you have any bad habits?

Peter O'Toole (00:41:11):
Besides not communicating when you're getting on with Google

David Piston (00:41:14):
I mean, other than other than coffee and wine, probably not.

Peter O'Toole (00:41:22):
Is that red or white wine by the way? Sorry.

David Piston (00:41:24):
Yes. By all means depend on what I'm having. You know, when I was, when I was in Italy, I, I worked at the Tron in Italy when I was in graduate school. And there, they drink white wine in the summer and red wine in the winter and it gets cold. They get switched to red wine.

Peter O'Toole (00:41:40):

David Piston (00:41:41):
I thought that was, that was sort of symbolized, but I, I drink wine with food. So if I'm having something that's lighter or we, we eat a lot of fish, so we drink more white wine. But

Peter O'Toole (00:41:53):
Okay. Do you have any pet hates things that really annoy you besides?

David Piston (00:41:57):
Oh yeah. People touching my stuff.

Peter O'Toole (00:41:59):
Oh, what sort as in on your desk at home or

David Piston (00:42:02):
Anywhere they move it, they don't put it back, right.

Peter O'Toole (00:42:11):
Oh, I know someone just like it's so, so easy just to move just something on their car, like move where they're.

David Piston (00:42:16):
Well, you know, my, my my shampoo is in the corner of the, of the corner of the shower and it's at a certain angle, so I can reach over and pump it into my hand and my wife cleans it and moves it. And it's like, I pump it all over the floor. Cause I, I mean, this time of year, the sun's up, but in the winter, I don't ever turn the lights on. I, I go in and shave and shower without the lights on it's I'm a spectroscopist. Right. So

Peter O'Toole (00:42:38):
work in the dark.

David Piston (00:42:40):
I, I, you know, I worked in catastrophic darkness for, for three years as a post, so

Peter O'Toole (00:42:45):
Okay. I can empathize. That's you just thinking about the shower? We got different shampoos and shower gels or whatever. The two of us that are using it. And I, I like everything faced up in the right direction. Everything is a height order as well. So you can see everything. Yeah. Face up, turning in the wrong side. It's like,

David Piston (00:42:58):
Yeah. I mean, I don't care what she does with hers. You can have it wherever she wants, but

Peter O'Toole (00:43:03):
No, no, you can't just be plunk down anyway. It's gotta be face round. It's gotta look neat. Tidy.

David Piston (00:43:08):
Well, I don't care about how it looks. I just need to be able to hit it and have it go my hand.

Peter O'Toole (00:43:12):

David Piston (00:43:13):
She's got like about a 10 degree, you know, like a 10 degree

Peter O'Toole (00:43:17):

David Piston (00:43:17):
Mirror there. That's possible. Still

Peter O'Toole (00:43:21):
Book or TV.

David Piston (00:43:22):
What's that

Peter O'Toole (00:43:23):
Book or TV?

David Piston (00:43:25):
What? What's a

Peter O'Toole (00:43:26):
TV. What you prefer? Sorry. I'm still laughing. Oh, you, why don't you prefer a book or TV?

David Piston (00:43:30):
Oh well, I, I TV. I like to watch sports on TV. So sometimes I'll read a book while I'm doing it.

Peter O'Toole (00:43:38):
Okay. And I, I, you send me this one. So watch your,

David Piston (00:43:43):
Oh yeah. Well, this is cause I'm in St. Louis, right? So that's the St. Louis Cardinals. We went to go see the, we go see the, the couple of Cardinals games every year as my wife and I at the Cardinals game is we were, they were playing the San Francisco giants, which was my hometown team growing up. So we got good. We got good tickets for my birthday one year. And went there and

Peter O'Toole (00:44:02):
You get completely kitted out. Then you got the top of the cap and

David Piston (00:44:06):
Oh yeah. Yeah. Well, I mean, it's a, why not? I mean, it's a, it is, this is a baseball town, right? So you, you wanna, you don't wanna be the only person that shows up the game without the right cap and shirt on.

Peter O'Toole (00:44:18):
And what about your when it comes to movies, films, what's your favorite film?

David Piston (00:44:24):
My favorite, well, my favorite film all the time still is still probably star wars. Although I'll tell people that it's it's either the Wizard of Oz or Spinal Tap,

Peter O'Toole (00:44:34):
Why'd you do that?

David Piston (00:44:36):
Well, because, because I mean, those, I think those are the best films ever made, but my favorite film is still star wars because I just saw it at the time when I was, I was like 15 and, and it came out and it was like nothing we'd ever seen before. And

Peter O'Toole (00:44:54):
You know,

David Piston (00:44:55):

Peter O'Toole (00:44:56):
No, that's probably the best reason I've heard. Why, why you're not a Treky over star presume you were a star wars fan over star Trek then.

David Piston (00:45:02):
Well, I liked, I used to watch star Trek. I mean, I, but to me, the star Trek ended in 1969. There's no other star Trek there's

Peter O'Toole (00:45:11):
Ah, pick hard. Oh, next generation.

David Piston (00:45:15):
What's that?

Peter O'Toole (00:45:17):
Oh, just, oh,

David Piston (00:45:18):
We had star Trek. Why do we need to look? I just don't like, I mean, we had star Trek. You can have another show, call it something else.

Peter O'Toole (00:45:24):

David Piston (00:45:25):
It's not star Trek

Peter O'Toole (00:45:27):
That I, so I still love Picard [inaudible] Picard as well about ah, yes. Big fan of it. What about your favorite Christmas film?

David Piston (00:45:38):
Favorite Christmas film. Oh, the well either, I guess Charlie Brown or the Grinch. I mean, they're, they're I watch both of them every year, so I have both of them on, on seat, on DVD.

Peter O'Toole (00:45:52):

David Piston (00:45:53):
And I, I watch both of them.

Peter O'Toole (00:45:55):
And drew, is that a family thing? You watch it together?

David Piston (00:45:57):
I make everyone watch it. Yes.

Peter O'Toole (00:45:59):
You make everything. Watch it. Good grief. Have we got family films and it's like, dad, we getting that close to Christmas. We've gotta watch them now. We've gotta watch them now.

David Piston (00:46:08):
I've never it's if dad wants to watch it, nobody wants to watch it every once in a while they discover something like my younger daughter discovered the song killer queen and so I got my old LP out and played it for her.

Peter O'Toole (00:46:26):
And then she stopped liking it.

David Piston (00:46:28):
No, no, she still likes it. She still likes it, but it was like, if I pointed that out to her, she would never have liked it.

Peter O'Toole (00:46:33):
Yeah. It's the trick. Isn't it. Make sure they make sure they think it's their decision. That that's what they like. That's a management skill. Get people to think it's their idea.

David Piston (00:46:41):
It's their idea. Yeah.

Peter O'Toole (00:46:43):
So moving off the, the more like ones still talking about favorites though, do you have a favorite publication that you've authored or co-authored for whatever reason? Oh, most memorable, favorite or most memorable?

David Piston (00:46:56):
Well, I guess my favorite one is the nature methods, GFP article we wrote with Mike Davidson. I mean, Mike had passed away at the time when it came out, but that has absolutely every, you know, it has every bleach bleaching for every bleaching and, and expression and brightness for every GFP that was available at that time. And it's still, you know, it's it just was a tour to force in so many ways, but it was all of the, was all done correctly. Rigorously. The way is hard, hard to get when you see a new GFP come out and you look at their measurements, it's like, I have no faith in them at all. And you can see you compare, compare what we've had to the what's was reported in the literature. And some, some people are pretty good and some people are really sloppy. And it was done by, you know, four or five different people in two different labs. So it was really always there was a ton of data. And that was, I mean, there was, I still have all the data it's on 40, I think 42 terabyte discs lots of them.

Peter O'Toole (00:48:07):
Good grief. That's a lot of date. It's a lot for us and proteins, but that's a lot of data still.

David Piston (00:48:12):
Yeah. Well, I's got all the, it's got all the images, all the original images, all the photo, bleaching, the cells with widefield and with spinning disc and with confocal, with laser scanning confocal.

Peter O'Toole (00:48:22):
Yeah. We talked about quantification and the importance of data. And actually, I, I it's almost mind blowing cause I, you know, I've looked at designing similar experiments in past, but actually it's fraught with challenges and difficulties and normalization and everything else. I've got to say, it's quite an achievement to have got around those problems. Yeah. And found a solution for it. It is not, it sounds and looks on paper so trivial. I, I, I don't mean to.

David Piston (00:48:50):
Yeah, no, no, I, I agree. I agree. It's in fact it's, it's sort of straightforward in many ways, but it's, but it's hard to get, it's hard to get the details. Right. I know when, when GFP first came out you know, I said, oh, we, first thing we gotta do is measure the quantum efficiency and the brightness and extinction and photo bleaching. And if photo there's a little bit of photo conversion in the, in the original between the two states. And we wanted to see, they knew if they hit it with UV, they could make it more, more blue absorbent. But we also discovered if you hit a blue, you could also make it more blue absorbent. And we wanted to get those two, the quantum yield of those two down, and we published this and everyone was like, oh, and I thought, for sure everyone was gonna be doing this. And, and everyone was like, oh, David. So I'm glad. So, so glad that you did this. So I thought everyone would be doing this.

Peter O'Toole (00:49:41):
So that's your favorite publication? What about your favorite, favorite microscope technique? Do you have one?

David Piston (00:49:47):
Oh well I guess I mean to, I don't have one, but it's gonna be some sort of lightsheet.

Peter O'Toole (00:49:57):

David Piston (00:49:57):
I mean, lightsheet really

Peter O'Toole (00:49:58):
Way technique. Just

David Piston (00:49:59):
Light. Yeah. Light sheets, the winning technology, right. Because it gives you all the advantages in terms of low expectation intensities. So lowers photo bleach gene is more gentle with the advantages of, of, of you know, 3d S spatials spatial discrimination. So,

Peter O'Toole (00:50:20):
So from the light or the more light hearty questions, what have you had, what's been the best time of your career?

David Piston (00:50:29):
Oh, postdoc. No doubt.

Peter O'Toole (00:50:31):

David Piston (00:50:32):
Yeah. I was in Watt web's lab. We were, we had a ton of resources. Two folks on had just been invented. I was probably the only person in the world working on it, cuz Winfried Denk had gone off to at IBM and was working on nearfield scanning with diamonds. And so we were doing this and people smart biologists were coming up and collaborating with us and, and yeah, I just went into the, went into the lab at 10 in the morning and turned the laser on and worked till late at night and turned the laser off, went home and ate dinner. And some people sometimes there'd be people there doing experiments with me and sometimes I was doing 'em myself. And

Peter O'Toole (00:51:12):
How, how did you mind COVID cause obviously the sample types would be quite varied on the multi on how did you cope with the varying biology and the, the way that samples were being presented? How did you, how did you adapt to that as a physicist at that point?

David Piston (00:51:26):
Well, I mean you know, so the weren't very many as we could do, right. We didn't have Ty Sapphire yet, so we really were stuck and GFP hadn't been invented, hadn't been cloned yet. So we were really stuck with calcium indicators. We were doing a lot of NADH and FAD auto fluorescence. So obviously doing NADH was one of the big things that we did and, and sort of pioneered and the Webb's lab went on to use that a lot with some of the people in his lab on neuro stuff, and we've used, we used it a lot on eyelets and, and muscle. We still use that as a, as a, as a sort of a standard standard technique in my lab and, and Flavin. So we used a lot of, we're using a lot of auto fluoresce. Um and so basically, you know, people, if they wanted live cells, they needed to come make them themselves. So John Lederer, who was working on cardiac myocytes, came up with a post doc and they this was in a day and age before iacotes existed. So they just order, they ordered animals and maybe brought 'em up with them or, or ordered them and picked them up at at Cornell and took the hearts out and isolated the cardiac myocytes right there. And we had them on the stage and we just, we just worked all night till we retired and then got up early in the next morning, went to breakfast and came in and worked again. And you know, at the end of the day I went home and I, then I came back and analyzed data in the morning while things were warming up. And that was it. There was no paperwork. There was no, every once in a while you went to a meeting, you had to fill out your travel form, but it was three years of really nothing but writing paper, you know, taking data, analyzing data and writing papers.

Peter O'Toole (00:53:07):
Yeah. So the singular singular focus, I guess back then,

David Piston (00:53:11):
The other thing is the other thing is, well, the postdoc, well, I had like four or five different projects, but they didn't have to be related as a graduate student. You can't work on something, that's not gonna go in your thesis. Well, I guess you can, but it doesn't help you that much. Right? Yeah. So as I always said, I, I called it graduate school for a reason cause I wanted to graduate

Peter O'Toole (00:53:31):
so they're the best times what's been the most difficult time you've had to face?

David Piston (00:53:40):
Well, I mean, not that I, you know, switching, switching from switching from physics to biology and having never been in a lab that had an RO one, which is the main NIH funding mechanism here was really quite difficult. Although I had a lot of support from my department we were publishing some papers and, and obviously two photon was very high profile. But it was hard to get grants until we got some biological results. Right. So I guess in hindsight, I look back and think that should have been a lot more stressful than it was, but I was, I was working all, I was working as hard as I could. And, and, and as it turns out probably doing the right thing I mean, obviously I think COVID was just really hard mentally on everybody. And you know, it was comped with the American political situation at the time, which was stressing out my family a lot as well.

Peter O'Toole (00:54:38):
Yeah. Different stress though. Maybe compared to the other environments. I've got a question now we're gonna lead to the next one. What's your favorite conference?

David Piston (00:54:46):
My favorite, well, I go to Biophysical society is my that's my, the first conference I went to as a graduate student that was in 1986. Oh, there's the presidents. Yeah. So this is so Taekjip Ha who's back in the back next to me is going, is the incoming president Gail Robertson is in the front right. With curly white hairs, the president now and Cathy Royer was president before me and and Francis Seperovic was right above you who was president after me [inaudible] was before maybe two before Cathy and Lukas Tamm was either in between or they the last two or, yeah. So that was that's you know, seven biophysical society presidents in a row there.

Peter O'Toole (00:55:31):
So what's the importance of that society for you? What role does it play that is so vital?

David Piston (00:55:36):
Well, I think I think for me, biophysics for me biophysics was where I learned that's where I met biologists where I met biologists, who wanted to be quantitative, where I met biologists, who had samples that would be useful to use with the latest and greatest techniques. So it's a, it's a conference that brings a lot of people that are tool builders. Like I was at the time when I was in, in graduate school or postdoc with people that are real you know, high end power users of the, of those techniques the sort of more quantitative bent biologists. Obviously electrophysiology is really big there. And so a lot of stuff that, that is single molecule sort of grew up in that, in that society. And so I think that's for me now, for me, I go there and I see the latest and greatest tools that people are building and think about what we can use on our, in our experiments. So I, I become more of a, maybe more of a power user of of, of technology than a developer.

Peter O'Toole (00:56:44):
And of course, I guess it enables you to travel as well. Cause you said, I think you said earlier that travel was

David Piston (00:56:50):
Well. Yeah, but I mean the biophysics meeting, of course, this last meeting I went to, in fact, this meeting, this is in San Francisco this year in 2022 was our first meeting back in, in two years. And you know, that was the first meeting I had been a, I was a civilian in forever. So I joined the editorial board of biophysical journal around 2000 probably, and was involved in different things from that time on so about 20 years, I was always busy at culminating and being president in 2019. If you're president at the meeting, you, you show up on Friday and you leave on Thursday and in between your schedules full . So you don't see a lot of things. And so it was nice to be able to go see talks and to, to make notes about a poster I wanted to go see and then actually go and see the poster and talk to the people

Peter O'Toole (00:57:43):
And then the importance of it being in person.

David Piston (00:57:46):
Oh, I think that was, yeah, I think absolutely critical. I think it's all, it's all the hallway conversations you know, I wanna re the other thing I do at the meeting is recruit people. Like most of my good postdocs have come from that meeting. I don't know most, but certainly a lot of them have come from that meeting. You know, you see people that are, you see people doing things that you are interested in and just asking if they're what they're doing next. So if they're a student and then you see their, you see their PhD advisor around the corner and you get a instant recommendation and then you, you invite them to dinner and you can just casually talk to the person to see if this, the kind of person that you wanna have in your lab introduce 'em some of the people in your lab have the people in your lab go by.

Peter O'Toole (00:58:34):
Now, you're gonna ask me to edit that a, because now everyone's gonna want to be asked to, to go for dinner with you at the next BPS meeting.

David Piston (00:58:40):
that's okay. That's fine. That's fine.

Peter O'Toole (00:58:42):
And you did send me a couple of other pictures we're really close to running outta time. So do you wanna describe what we can see?

David Piston (00:58:48):
Oh yeah. So this is, so this is the, this is really what I do outta my spare time. So I, I was I used to sing quite a bit. I mean, I still sang a little bit, but after I, after I turned 50, my voice wasn't quite in the shape. It was, this is Nick Meegan, his a famous conductor, he's sort of a Mendelson scholar but does a lot of rotor. And I sang the Messiah with him a couple of times. This was him at the St. Louis symphony. He was I don't remember what he'd done that night. What he had done that night, but we had a reception afterwards for him. I'm involved in the board of the St. Louis symphony. And so we had a reception for him. And so he's my favorite conductor I've ever sang with. Uh we did, like I said, we did the Messiah with him and he's, he's said one of the, one of my favorite lines of conductor had ever said is there's a, there's a line in the Messiah, which is even so in Christ shall all be made alive. He said, that's the most important V in all of coral literature, cuz otherwise you say even so in Christ shall all be made a lie. And as a, as a singer, you know, working a lot with making sure your addiction is right. I thought that was very,

Peter O'Toole (00:59:55):
That's quite a good

David Piston (00:59:56):
One. A very clever thing I really liked. I really liked.

Peter O'Toole (00:59:58):
So I didn't know about it singing to just so I'm glad I brought this picture up. Yeah. So the next one.

David Piston (01:00:03):
Yeah. So this is, this is Sulu. This is my star Trek and this is Joyce Jaka. And this was, I was actually singing with the Nashville symphony at the time. And we did Schonberg piece survivor survivor of the ghetto Warsaw. And George was the narrator of that. And this is an amazingly powerful piece that was written by a man who hid underground and they drug off, they killed everybody and he was left behind and, and survived. And he heard, he heard all of Jewish men as they were being killed, sing the, the Jewish song. And and so that's what it's about. George was the narrator and his family was, had been held in the Japanese internment camps in the world war II. The Americans had set up and so it was really a, it was a great emotional night, but it was a, a, I wouldn't say a fun piece to sing a very challenging piece and something that, you know, never, it is the kind of thing you never, you can have a recording of it. It will never have a power of a, of a live performance of it. And so, yeah, I sang, sang with the Nashville symphony chorus for 23 years when I was at Vanderbilt and I sang, I sang professionally when I was in graduate school mainly singing commercial jingles because I didn't get paid very much as a graduate student. And not that I was saying, I wanna remember to say,

Peter O'Toole (01:01:30):
Oh, about to say, you've gotta give us a jingle. No, no,

David Piston (01:01:32):
No, no. I'm not gonna, it was one that, something, the words were we're number one in the number two business. And that's not all you need to know about it.

Peter O'Toole (01:01:39):
that so intrigued. Now I should have asked this, I could coming back to this to try and get a jingle off you all the way through little jingles that would've been really cool.

David Piston (01:01:50):
I've I've wiped all those from my memory. Most of them were pretty darn bad.

Peter O'Toole (01:01:54):
yeah, quite no. That's okay there. And I guess these are,

David Piston (01:02:01):
Oh, that's Maine. That's my that's the cottage I stated in, in Maine for 20 years when I was teaching the course up in Maine. So this is to remind me about teaching my cross. That's what the fish picture is. That's the cottage. It meant there's not only a biological lab. I every day, every year I was there, I took a picture like this. And I think most years was one day. That was nice enough weather to take a picture like this.

Peter O'Toole (01:02:23):
It's not always like that then.

David Piston (01:02:24):
No, no, no, no, not really. There was one year where it was horizontal rain all year, and this is that's the sunset at the same place. That's at MDIBL

Peter O'Toole (01:02:32):
The same day, you got a nice day once over. So finally we are up to the hour and I can't believe we're up to the hour. And we talked about the importance societies, go on. What's the next big step for your research? Or can you not say about this?

David Piston (01:02:49):
Oh, well, I mean, you know, we so really we found these, we found several pathways that influenced the alpha cell Glu glucagon secretion. So insulin is the hormone that everyone knows about that comes from the pancreatic eyelet, but glucagon is the counterregulatory hormone which when insulin goes up, glucagon goes down and importantly when insulin when insulin goes down and there's low glucose, glucagon goes up to tell the liver and then to make more glucose and tells your body to release it and stop taking it up. And in the presence of insulin, glucagon, isn't so important. It's more of a fine tuner, but in the absence of insulin, either in type one diabetes, when the beta cells are killed or in type two and insulin just fails, it turns out that glucagon is plays a very important role. And what happens is instead of it going down, when it's supposed to, it goes up and it, it makes things worse. So we've been working on that on pathways. It's not understood exactly what regulates it normally, or, or even in diabetes, but we have some pathways that we think can regulate it, whether they're the ones that normally regulate it or not that can regulate it in diabetic situations. And so we're trying to screen for drugs that will hit those pathways. I would really like to know how an alpha cell works, but people have been working on that for 45 years now. And I don't think that we're any closer than we were 45 years ago. So I, I don't like to set goals that I'm probably not gonna reach, but I think we can actually have some potential drug targets that would be worth exploring for tr treatment of, especially if type one diabetes you know, at type two diabetes, I know how to treat just get some exercise. A lot of people get obese and don't get type type two diabetes. And those tend to be, you can be very obese if you're still moving a lot. You're probably not so prone to getting diabetes. So it's a disease not only of, of high caloric intake, whether it's obesity or sugar or, but there's also a, a, a sedentary component. And unfortunately, but that's why we need more in person conferences. Cause you, you're not sedentary at, in person conferences as much as you are at the zoom conferences.

Peter O'Toole (01:05:04):
I, I was about to ask, what is your exercise then to keep yourself fit, keep yourself healthy.

David Piston (01:05:08):
Well, I mean it's no elevators, so I take the stairs a lot. I, I walk pretty fast. I, I ride I ride my bike if I can. I mostly ride my exercise bike though. I watch watch in the fall I watch football and ride my exercise bike for, for I, I watch basically wa for about an hour to an hour and a half try to put 20 miles on the exercise, bike, while I'm watching football. Cause I was like, like I said, I can, I can, I like to watch football, but uyeah, world, world. Cup's always good for that. Right. When you're watching the world cup, I mean, you have to be doing something else. If you're watching soccer it's

Peter O'Toole (01:05:51):
Yeah. Drinking beer.

David Piston (01:05:53):
Well, you can do that too, but you can drink beer for half the game and ride, ride the exercise bike for the first half and then

Peter O'Toole (01:05:59):

David Piston (01:05:59):
Beer for the second half

Peter O'Toole (01:06:00):
Undo all the good stuff on the second half of it. Dave, if we have to call it today, cause it is up to the hour now. Okay. Thank you so much for joining me today. Everyone. If you've enjoyed watching, listen, please, don't forget to subscribe. Go back. There's loads of tips and tricks in the previous episodes that Dave's actually alluded to throughout this. Dave, you've been really great to talk to some really great, I think that last bit and where you are going to, how you've moved all your physics knowledge through to actually now going into diabetes research, I think, I think is quite good and a really great case for many watching to essentially follow your passion, follow where, where follow, where you can succeed and what you're interested in.

David Piston (01:06:39):
Yeah, I'd just say be a scientist, not a physicist or a chemist or biologist. Just be a scientist.

Peter O'Toole (01:06:44):
Ah, lovely phrase on that note, Dave, thank you very much.

David Piston (01:06:48):
All right. Bye Bye

Intro/Outro (01:06:51):
Thank you for listening to The Microscopists, a Bitesizebio podcast sponsored by Zeiss microscopy to view all audio and video recordings from this series, please visit bitesizebio.com/themicroscopist

David Piston (WUSTL)