Wah Chiu (Stanford University)

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Intro/Outro (00:00:01):
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 Wah Chiu Professor of Bioengineering and Microbiology and Immunology at Stanford University. And we discuss his groundbreaking work in Cryo EM and his future research goals.

Wah Chiu (00:00:28):
So my ambition is, is somewhat modest, but practical in the sense that I want to understand the organelle in the cell. Yeah. Okay. Now every, you know, cell biology they know organelle because that's what the textbooks teach them. But I don't think we really do.

Peter O'Toole (00:00:45):
We discuss this awesome approach to mentoring students.

Wah Chiu (00:00:49):
I think the fun thing, being a professor to have an opportunity in there with the students, I think that's the funest part of the job. So, you know, I feel the important thing is to learn from the student through their questions that will inspire my way of thinking.

Peter O'Toole (00:01:06):
We also delve into the potential future of microscopy in this field.

Wah Chiu (00:01:11):
That is the current state of art, but there, of course there are many yet to be developed technology that I would say a five years from now. Some of these would these picture will be replaced by another pictures, bigger, more expensive, most ID maybe even taller

Peter O'Toole (00:01:32):
All in this episode of The Microscopists. Hi, welcome to The Microscopists I'm Peter O'Toole from the University of York. And today I'm joined by Wah Chui from Stanford. Wah. How are you today?

Wah Chiu (00:01:52):
Very well, indeed. Thank you. Good morning.

Peter O'Toole (00:01:56):
Yeah. Good morning. Good afternoon. Good evening

Wah Chiu (00:01:58):
Afternoon. Yeah,

Peter O'Toole (00:01:59):
thank you for joining me today on this. I I've got to say I've seen you talk not that long ago, actually, but I was also strongly encouraged to talk to you on a more personal note there from the likes of Lucy Collinson who, who are big fans of your own? I, I, where to start actually, I'm gonna ask what, what was your first degree you are known for your structural biology, your biological studies with electron microscopy, but what was your degree to start with?

Wah Chiu (00:02:34):
Okay. My first degree is in physics and then at that time, when I finished my first degree, I was thinking, what do I do in the rest of my life? And in those day I was only pursuing what would be exciting to do. I wasn't thinking about money or position. I'm just thinking, what's the next thing exciting to do. And that was doing the rhythm wall era. So every deep students at that era start questioning the relevance of their studies or whatever they're doing. So I thought maybe I want to solve the cancer problem. So that was my really like way of thinking. And that's why I said, okay, then what do I do if I want to solve the cancer since I'm not a biologist, so maybe something I call biophysics. And then that's what I get into biophysics as a graduate student

Peter O'Toole (00:03:36):
That, so I said, so my PhD was also in biophysics and there's a big difference between physics and biophysics. So that's a huge jump between the two. How did you find that, that transition?

Wah Chiu (00:03:53):
Okay. So it's interesting because turn out most of the faculty in biophysics at University of California, where I attend the graduate school were physicists once upon a time. And so as result, their emphasis was always in the physics principal in solving biology, they placed more emphasis on the physics aspect of the biophysics, then the biology aspect of biophysics. So as we saw my old upcoming in that training was thinking more, you know, what can I do understand biological system music to physics principal. So that's where I come from. And then of course I need to make up all the things I did not know. So I took all the courses in cell biology, Monica biology, and genetics, and the like, so that's, that's my exposure in biology. I would say my biological background is good enough to me to be a professor in bio X and Y but I'm not really [inaudilble] biologists.

Peter O'Toole (00:05:09):
So if you had a choice and you could only do biology or physics, which would you choose to do now?

Wah Chiu (00:05:18):
I think it would be a good idea to do the physics to start with. I think that give you a quantitative background and analytical backgrounds, and then you do the, and then you pursue the biology. But I would have to say the, the world of biology also changing. So there could be some undergraduate program maybe more integrated because now I encounter some of the undergraduate student at Stanford. Those guys are really sophisticated they actually, they not, they know enough physics and they know enough computing and they also know the biology. I think that the, that the future of, of integrated biology, I think the future biology, I was considered to be integrated biology that would encumber what we believe for a long time, but now in manifest in a different way, physics, chemistry, and computing, mathematic and biology.

Peter O'Toole (00:06:21):
Yeah. I, so on that front, we reflecting on it. I guess biology is, is something that you do need chemistry, physics, computational mathematics, they all come together underpinning any, almost all biological biological studies that I can think of. I, I'm struggling to think of an exception where you don't need at least one or two of those skills in appreciation.

Wah Chiu (00:06:46):
I agree fully. I agree fully. And so now, even in my research, we initially start of course from my Cryo EM angle to solve the structures. But at the end of the day, after with the structure, we need to understand it, it get me into computing, it get me into really biology. So, so, and then I think we can think about a step further actually in medicine as well, so in the past we thought, okay, we write grant. We justify because we will solve problem X and Y. But now I think it's real. I don't think it's a fantasy anymore. I think that integration of Cryo EM, and Cryo Electron tomography into biology and medicine is real. And of course we need a lot of computing and AI and also physics based in to make sure what, what we are concluding or what we, what we are making the models are correct, at least chemically. Correct. So again, we need to chemistry. I mean, one fascinating thing. Recently, I begin to know that God I need to go back to learn the organic chemistry myself. You know, that's all the fundamental thing, which I learned years ago, but never been used. But now I, you know, I find very fascinating from that point of view.

Peter O'Toole (00:08:17):
I think I'd find my organic chemistry quicker to pick back up again than some of my maths or physics. I, I, I guess I was, I, I guess biochemistry's degree. So there was a lot of organic chemistry drummed in, yeah. At that point you mentioned computing and simulations. So obviously all your work at the moment is heavily involved with Cryo electron microscopy, but you you've got things like alpha fold, which is essentially a computer. You can put your sequence in and, and it will predict the sequence. Do you see a risk of that? Replacing the need for cryo EM infrastructures?

Wah Chiu (00:08:55):
Not at all. They need us even more badly than ever. Okay. And I, you know, when you think about all the alpha fold is, is because the knowledge that the [inaudible] had been able to accumulate in the last 50 years, you know, that provide a lot of database about what structure would look like protein, X, and Y, and that the AI to learn it and then P dig it. So, but at the end of the day it is important. Particularly we talk about chemistry, we talk about the local environment. Okay. And need to be precise. And it could be changed because the alpha fold, I think I understand they can now predict more than, you know, one confirmations, but exactly which one is correct. Okay. I mean, CSN has simulation. You can simulate using a Mono dynamic to simulate this market move from a to B. Right. But how really is in term is function. QMI the purpose of our research is to understand how things work. And after we understand how things work we can, where we can manipulate for better or for worse. I mean, that is the purpose. That's the way I think about the purpose of research is we understand now we can regulate it. We can control it is harmful to us and other organisms. Okay. So, but I don't think alpha fold is is, is can solve our problem. Now I would confess alpha fold become very convenient. If you have an unknown, you can predict what that is, and you can use that informations and then to help you to get the ground tooth. So keep in mind, our research is get the ground tooth. So alpha fold in most cases would not give you the ground tube in understand is function in context.

Peter O'Toole (00:10:57):
And it, it, it is an amazing bit of software, but I, I, at York, as I, I, I mentioned earlier, my office looks out on the new Cryo EM building that's there. So, so certainly we are, we are using alpha fold, but also certainly our structural biology. So very heavily into their cryo naturally into their Cryo EM as well. I've gotta, I, you sent me some pictures, which includes,hopefully this works. So for those who are watching or listening,what the picture's actually showing,I think an SCM on my one shoulder, but then it's a huge actually, is it? It's not it, but you've got the large TM, Cryo TM as well, which is really tall. I don't think you can appreciate from this picture just how big it is at this point, but what was the first microscope that you used?

Wah Chiu (00:11:54):
Okay. My first microscope that I used was a microscope did not exist, actually. It was made by United Kingdom company called AEI. And I couldn't remember what that abbreviation stand for. And in the old days, the British company, there's a British company make that microscope, a transmission microscope, a hundred kilo was a very powerful microscope because larger microscope microscopy knowledge and foundation was laid by pioneer at both Cambridge and Oxford. As I recall, particularly in Cavendish lab, which I have the previous to spend some, some months when I was a student there. So I still remember that good time. So, so, but nowadays the one, the picture on the right is very tall. Microsoft is a 300 kw transmission microscope, and that is what most of the hardware solution Cryo EM structure being used to generate the images. And the picture on the left is a focus I'm being scanning the microscope, which is to to micro machine, a very thick cell in the thin manner so that you can put into the tall microscope to do tomographic data. So, you know, in the next few years, these two instrument are kind of hand in hand. One is more or less a specimen preparation. It's a very expensive specimen preparation device on the picture, on, on my left or on your right. And then the other one is to do for the generated tomographic data. That is the current state of art, but there, of course there are many yet to be developed technology that I would say a five years from now, some of these would, this picture will be replaced by another pictures, bigger, more expensive, most likely maybe even taller.

Peter O'Toole (00:14:08):
That's interesting you say that. I, I, I was gonna say, cause obviously I, I did a podcast with Richard Henderson as well, and he was raving about the 100 KB systems that Muhammad El Gomati has certainly been doing a lot of work with. Right. And I, I I'll ask you a take on that in more detail after the podcast, obviously, but sometimes. So I

Wah Chiu (00:14:30):
Would be happy to comment on that if you want me to respond to Richard's hypothesis.

Peter O'Toole (00:14:35):
Oh, go, go on there.

Wah Chiu (00:14:37):
Okay. So first of all, hundred kilo instrument is a fantastic, good instrument. That's all we got started. Right? So I started using the a hundred kilo instrument to image protein crystal at three and a half sums and collect defection pattern or protein crystal to 1.5 that was done in the, in the late seventies, early eighties. So that suggests the physics definitely allows one to get the data of atomic resolution. So what, what Richard suggests using hundred Kw is not a crazy idea. Okay. And of course he is promoting based on very strong physics base, but evidence in the literature upon that to support his hypothesis. Okay. But I think on the other hand, the single par there are two area, two types of specimen. One we call single particle, small little molecules. Like if you are interested in seeing an RNA molecule of 30 kilo down, so 40 kilo go. And I think that is the kind instrument is well suited. Okay. So one of the excitement that Richard recently developed or developing is to have it detected that we can collect data efficiently and effectively. I think several years ago, I don't think it is too useful because I worry about the detectors. Okay. Because all the detector are fitted to this expensive, tall microscope behind you. But I think now that couple company, including Richard himself developing detector can get, we able to color images. So, so all these, the last few decades, the few hasn't been advanced because the, the, the Microsofts are good, but we cannot collect the data. You know, there are no medium to collect the data and, and, and also the BI me news movement, but all these technical issue has been graduated. I know. So I would say this is probably a, a viable instrument. Okay. However, what I see the futures of the structural biology cell, structural biology. Okay. Why now is molecule structural biology and definitely a hundred kw old would do it like, as I mentioned, small RNA, small enzymes, small proteins particularly if a lot of drug design area, a lots of these drug target, maybe 50 KD or 60 K kilo dins. And I think hundred kw, would definitely, will be well suited at that. I would agree with, but on the other hand, what I'm thinking of is looking at a bigger area of the wholesale. Now, of course, this very business sale has too much stuff to bake. We can do it. At least we can see personal itself. So my ambition is, is somewhat modest, but practical in the sense that I want to understand the organelle in the cell. Yeah. Okay. Now every, you know, cell body default, they know organelle because that's what the textbooks teach them, but I don't think we really do. So I think the excitement I would consider will be ag considered to be organelle structural biology. Okay. Now, in that case, I think we need these tall Microsoft maybe even taller. Yeah. Okay. That means, you know, because at that tall one, I I'm interested, atomic resolution always did and still do still do, but I'm interested in a lot of this molecule in the context of cell. So even as sub nano matter resolution or nano matter re resolution, I think I will learn a lot, particularly in the context of medicine, in pathologies, in cancer, neurodegenerative diseases, infection, biology. I think there's so much, you know, it just around our fingertip, we can just go to make all the discovery today, next 10 years, full time. Okay. so, so in that sense, I say, Richard, okay, I agree with you hundred Kw will be valuable, but I think at a high, low, like these 300 or even 600, maybe one MV would have, is display in right now or in the near future.

Peter O'Toole (00:19:19):
Now I think you intubated, they're addressing different problems. They're looking at different sample types. And one of the problems I was going to ask you, actually, one of the problems with the instrument behind you is the cost. It's not easy to get, you know, confocal microscopes have come down in price. You can have multiples of these at most universities. But the Cryo EMs is not for every university still. I think the reason I was a bit coy with the, the 100 KB systems, I know Richards talks a lot with Muhammad El Gomati of York probe solutions. I, I, I kind of know them quite well. Mohammad was only one of my grants applications once. So, so I didn't wanna vire towards that direction, but I think it's a really interesting solution for enabling most universities to get something, to do some of the low hanging fruits, some of the easier, easier sounds wrong. Doesn't it. I'm going get into trouble saying that some of the, that side of the market, smaller molecule.

Wah Chiu (00:20:22):
No, I, I, I agree with that. I think that will de democratize some of these research activity and the fact have been able to sell, I was still over 300 that this, this Cryo, okay. The tall instrument behind you. Absolutely. And the question is I didn't expect that people would come up with that much money. I don't know where the money come from. So I think in a sense, I'm not too too concerned about the economic aspects. The fact that, you know, the industry show me, that they're able to sell. And then my colleagues around the world capable of raising all this money. And so I'm less concerned about that. Now think about the hospital, at least in America. Yeah. I mean, how equipped they are, you know, they have a CT scan and all this, it will cause probably as much as this qui there's no problem. And I can, you know, when FMO Fisher in a few years ago, they say, oh, they want to make money. They want the farmer to have this kind instrument. I said, you think too small. You need to think about every hospital in America need one or two or three. Then you are talking my language if you really want to make money. So, so I, I think at least I'm looking from American economy, point of view. I'm not, you know, I think it's hard to get the money now for people who are interested in doing research or don't want to waste time to raise money. You know, like what I do, you know, I'm wasting a lot of time in managing this at the moment. I think it's a gut community service. The way I look at it is that the funding agency, the government like, like the Epeg over in diamond light sauce and I think needs to some extent, or maybe in, in Edinburgh, not Edinburgh, sorry, in Glasgow. And then like in us, in America, the I sent, so we set up all the Senate, just like the x-ray beam light, right. In the past, nobody can afford the x-ray P nine that really make that make that possible. You really will Ize the whole view in Monocle structural atomic biology. Right. So, so I think then the problem is why people don't want to do that. It just think about the American style or leaving. Everybody want to own the car, not only one car, two car and three cars. They never want to take public transportation. Why it's a cultural thing. Right? So by other part of the world, they take bus, you know, they walk to the bus stop and they take the bus to work and take they take the bus home. So I think the American scientists need to think about that way. They don't, you don't own thing. You use things and then you, you can, the goverment would pay you to, to use the thing freed. And I think that once you have the culture shift, then I think will be perfectly fine. And so like the place like EPEG and like some of the center, you know, you know, because not just buy the instrument, but getting the people to run it.

Peter O'Toole (00:23:37):
Yeah. The expertise

Wah Chiu (00:23:39):
Expertise. And nowadays all the company begin to do it. They pay people. I was told 2, 3, 4 times more. I'm losing people. I'm actually joining the people. They go to industry making more money than I do. You know, what can I do? Right. I mean, they want, you know, that's the way you go. But on the other end, what I pull, what I can provide is I consider, I'm sure you feel the same way, our interaction with an Ironman, something exciting. We make discovery. And we interact with people freely and we exchange things freely and we don't have a boss over me and you, you know, every day. Right. So that's what, you know, what, that's what we are. We are compensating with with less pay. So I think, you know, we would just have, you know, like Richard, you know, have even volunteer to work, you know, without pay, you know, this, we have these people and don't worry about it.

Peter O'Toole (00:24:34):
I, I was having that very discussion actually early on with a colleague and we were talking about different posts and how much they get paid in different parts of the country. And if you got Google right next to you and how much they would pay for the similar type of post. And then I say, well, so, so, and actually academia's trying to increase the salaries to match and fascinating someone again, different conversation. But someone else said, actually, we shouldn't be trying to increase our salaries to match that. We should be paying parity salaries to the other academics that Google aren't gonna poach or whichever big company isn't going to pay. I'm not picking on Google here at all. Because actually those who want to go into science and help you got into it to help solve cancer. Yeah. People who are passionate about the science, it's not about the money. Yes. We have to make sure there's a, a good salary there. Absolutely. But at the same time, they're not going to be there because they're getting paid more than they get paid elsewhere. They're there because they're getting paid well, hopefully. Yeah. But they're also doing something they're passionate. It's, it's not a job. It should never be a job in academia.

Wah Chiu (00:25:42):
It's not a job. I'm

Peter O'Toole (00:25:47):
So it is, it's gotta be a passion, hasn't it? It's gotta be a

Wah Chiu (00:25:52):
Agree. I agree. Yeah. Yeah. But definitely like in our area, it's a very water tight, because we are one, we are as expensive as living in London now, even more. So it's, it's, it's challenging. Just the cost of living is much, much higher. So now we are surrounded by the Silicon Valley now with Facebook and Google, you know, I mean, it it's challenging.

Peter O'Toole (00:26:18):
Yeah. But, but I think the best people who want to help will still be there. It's just, it's the cost is the cost of living around it. That's going up so much that, that makes it yeah. More, more challenging at that point. Now I I'll I'll change subjects a little bit. I'll just go back to that previous picture which was of you, you mentioned public transport compared to having your own car. Well, I would argue you are public transport cuz you have these instruments that are also used by many, many different people and they're not owning their cry, own Cryo EMs. You know, we have our core facility at York,which is now Europe Bio imaging node. So people from all over Europe can come and use that infrastructure and because they can't, or don't want to afford technology moves on so fast, right. If you were to buy a car, you know, you're gonna get five, 10 years, whatever out of it in this case may last two years. Right. And better comes out. And if you're not using the best, your science is no longer cutting down.

Wah Chiu (00:27:22):
Right. Exactly.

Peter O'Toole (00:27:24):
So you started core facilities or, or the structures of putting in shared, shared labs of the EMS. When was the first time you, I think you did this back in Baylor, did you, am I right there,

Wah Chiu (00:27:37):
Right? Yeah. It's of almost 40 years ago. You see, because for decades ago ni has a division that, that explicitly fund these cutting edge technologies for technologies that is not yet proven, but through that support to prove that technology to be useful. I mean the technology, including the x-ray beam nine the NL, the mass spec and then the microscopies. And before my time it was the cell biology, the MBV microscope, like key port, I don't know, you heard of him, you know, the, it is a very senior cell structural biology discover a lot of thing in the cell. And here has a one MBV microscope in BHA. And the time I came in and I was questioning, you know, those old one, MBV microscope would be useful or not. And some of us, including me on the committee, we fought perhaps a three fee, a 400 kilo would be a intermediate choice because they are, at least it can fit in the, the normal, well, a little bit taller sitting, but not, you know, two story height. And so, and so, and I, you know, was willing to fund me and a couple other sites to acquire those. And I was the only one that was pursuing the choir. And so, and, and, and that is how I get started. So mostly developing the methodology when I first started with the 40 enzyme food a year from 40 enzyme to now, you know, one point twoish and some resolution, you know, that about feet three and a half decades effort. And so, so it is not an overnight thing in this kind of activity.

Peter O'Toole (00:29:37):
So thinking of those three and a half decades of setting up, what's been the best time over that career.

Wah Chiu (00:29:45):
Oh, that was a really phenomenon time because first of all, there was no competition for 30 years. I enjoyed that because people thought I was crazy that they left me alone so I could do what I want and I could do my own pace. So, you know, one of the exciting thing was I was able to use the instrument in, I helped setting up in, on this super contacting NAS microscope. And I was able to get images of protein crystal to, you know, better than four enzyme on images that was, that was exciting. And then that work actually I think, stimulate Richard to move into the imaging approaches. So I think that, to my opinion is, is I was excited at that time. I went there to do the experiment myself. I helped setting it up. And that was the last instrument made by semen corporations since then they company out the business. And so that was a good one. And then at beta, I was pushing on a 400 kw microscope. So we decided at that time we wanted to go on single particle and viruses. And we work with, I spent a year on sabbatical at the R B and then get to know a [inaudible] and I get involved in working with herpes. Okay. And so Richard is always a very good friend of mine. And so I spent a year with Richard and Tony Calver and [inaudible]. That was probably the most enjoyable year on Sago. That was a very memorable time in Cambridge.

Peter O'Toole (00:31:24):
I, I presume that was, so you sent me some pictures of you and Richard as well. Which hears, I presume this was after that period though, or was that during in that time? Surely this was after

Wah Chiu (00:31:34):
The pic, the picture I sent you was after more recent pictures, but it was, I know Richard, when he first discover the structure of bacterial adoption with Nigel Unwin. So we were back because we were one of the very few people interested in that approach at that time, you know, on protein crystal. So I was, you know was pursuing protein crystal rather than the single particle. And it was delightful that Richard came the visit after his prize in 2017. And then the two other people, it happened that day were to senior program office of department energy in Washington visit. And so they were delighted to be with Richard as well. So that was a really good time. So Richard has been very helpful to me all this year and encouraging me to do things. And of course I deviate from the original work, doing the protein crystal by betron defection. I switched to the single particle. So it was, it was not received by the community too well at that time because it was very low resolution, but I'm get what I did. So I was improving from 40 enzyme to 20 enzyme, to 10 enzyme, to nine enzyme to six enzyme and eventually to, you know, three and half enzyme four enzyme before the so-called revolution. But since I was working on bacterial phages, again, people usually don't pay attention. So-Called irrelevant, biological object. I wasn't working on sexy membrane protein. Right. So, but anyway, but I think for technology, I think it's important to choose the right benchmark molecule so that the technology can then sell to it. So I, I still well please what I do, but I think without that, the single particle won't be my opinion. And won't go that far. I mean, I was poising along at that, that period. So I think for during the period at Baylor, I, I developed the whole thing from 40 enzyme down to four enzyme that period.

Peter O'Toole (00:33:52):
So you said quite nicely that actually the last 30 years have been your best years cuz you know, you were, you were, you were alone, there wasn't any competition does competition now because it's, it's, it's boomed. You know, what you've been developing is being proven. Everyone has now caught this wave and surfing it, but take away the best times. What's been the most challenging time in your career today. I shouldn't say to date. Cause that sounds like you're gonna get bigger challenges ahead. What's been the most challenging time in your career, be positive on this one?

Wah Chiu (00:34:26):
Well I would say I have been really lucky and I haven't encountered any time that I need to suffer one way or the other. I mean I was because I, you know, one of the challenging aspect is how to get people, right? So, but I somehow I foresee that problem. And I foresee it now and I foresaw in the past. So I prepare for it and I will create my path to recruit people. So I welcome people and many of the people I recruit, you know, people might not be good to start with, you know, in never I'm willing to invest on the future. So I, I think the challenging aspect is to find colleagues who have, have the same belief in the scientific destiny as I do now. I don't want to say yes man, but I think I want people have the same goal, but of course when you do research, one should have all the degree of freedom to inquire and turn right, turn left or completely say, this is that project. We should move on to the next one and things like that. So I think the challenging is actually making the right decision go and no go in some of the projects.

Peter O'Toole (00:35:50):
So you sent me some of the pictures and it's probably relevant to bring this in now. And I, I think this is a big graduation ceremony. Oh yeah. So are you hunting around at this point, thinking who, who am I gonna poach? Who's who am I gonna get to come and work for us?

Wah Chiu (00:36:04):
Well, I actually, it's challenging way now for me that when I was a Baylor, I, I know I was in the medical school. I didn't have students, the student that I want as I point out, I prefer student physics, background and so I create graduate program at Baylor. So fortunately my colleague was kind enough to let me do so. And I, I, I organized not within my school, but also all the neighboring institution because in Houston, there are multiple institutions, including Rice university, university, Houston, which they have the undergraduate, they have the basic physics and chemistry and other math and computer science department. So I never get, we form a consortium and that's what I leverage my environment to have recruiting students that have common interest to the biophysicist computation biology. So I was doing quite well. In fact, I, you know, when you asked me about photograph, actually I come up with a photograph, which I didn't post to you which, you know, something like 40 plus people in the past, you know, many of them are very successful today in holding professorship in multiple school. So I was really looking forward to that. Now, one of my reasons to move to Stanford, I thought, you know, that would be an environment that the students should be, should be a premium, you know, types of talent that I can take on. But turned out is tougher than I think to get student at Stanford. Because somehow the Stanford graduate program run in a pretty restricted way. We don't accept too many graduate students. And as a result, the surprise is very limited and I have no control whatsoever. Now. That's why I still enjoy my freedom in Texas. You know, I say, we need more student, I just hustle for money. I can hustle it and I go to recruit and that would be okay, but in here I it's a more traditional institution. I York or Cambridge in Oxford, they have a decent, I need to follow the tradition . And so, so as we saw I, you know, like the, the picture you saw Wago the young students and she's in biophysics. Okay. And these students, one of my student graduated is also in biophysics. So I was lucky to have a few students in the last five years, but I don't see an overwhelming group of student coming. And I also don't see many people calling over to come to work for me neither. So, you know, I can imagine, you know, that people may have more choices these days. Number one, and number two, the cost of living in the Baylor, maybe too high. And number three, they may think, oh, why I still it wrong? I thought he's retired. Right? So so the young people may want to work with younger faculty. I can understand that, but on the other end I'm still working 24 7. I, you know, I I'm okay. I survive.

Peter O'Toole (00:39:30):
So I was like, you say, you work 24 7, but you must do things outside of work as well. So what, what are your passions? What are your hobbies outside of work?

Wah Chiu (00:39:42):
Well, used to

Peter O'Toole (00:39:43):
Run, used to run didn't you?

Wah Chiu (00:39:45):
Well, I'm sorry. I, we don't have anything outside my work. I need to rework 24 7 even today,

Peter O'Toole (00:39:53):
But you used to be a runner, huh? Used to be a runner.

Wah Chiu (00:39:58):
Well, I know, but that is part of work. Right? you know, part of the exercise, I need to keep myself in shape. My only, only period that I do think is taking a walk in the evening, but even taking a walk, I used to have my cell phone. I'm actually talking on the cell phone when I'm walking. So that's what I meant. And so my wife are not too happy of that. She keep, want to take holiday and do things. So we haven't done enough of that. Except that once a year we commit that you have a pictures. Yeah. So few, few, few, few months, few weeks ago I went to London and I, Richard, I visit Richard and others at R and B, but I also went a day in London and I have a lot of relative this, my nieces and nephew and their kids in London. So that was fun that day. That was,

Peter O'Toole (00:40:58):
It's a very nice picture of, of, I guess your immediate or closer family, but you also sent me

Wah Chiu (00:41:03):

Peter O'Toole (00:41:04):
A bigger,

Wah Chiu (00:41:06):
Yeah. So we, we decided that we ought to have a holiday once a year. So I have two daughters and I have six grand kids. So this year we decided something simple in Northern California. So we, it was in, in, by this, behind you is the Pacific ocean. So we did enjoy that week. And so that was a good thing. And in fact, several years ago, we even spent a week in London together. We also enjoyed that very much indeed. So, so that was my, yeah, my day off that week. Yeah.

Peter O'Toole (00:41:44):
And, and I've gotta say, you're looking very dapper very smart in this one. So what, what, what is this picture?

Wah Chiu (00:41:50):
Okay, so that during the, the, after the holiday, one of the, one of the grand niece got married and so this was in the wedding. That's why we all dress up. So the, the, the ladies next to me is my granddaughter. She, she's a sophomore at the university in Georgetown, in, in England. And the one in the middle is my second daughter Andrea and she live in Houston. And then the ladies next to her is our niece. And the, the far side young lady is my other granddaughter. I have two granddaughters. So they all in the pictures. And in fact, this young granddaughter now they today they're in Philippine, my daughter have moved to Philippine for three years. So she's now in Philippine.

Peter O'Toole (00:42:52):
So I, I have to share show these picture just in case you've missed someone and you, your name dropping them all. And if I miss one out, you'd probably kill me. So the, the, the one final family photo

Wah Chiu (00:43:03):
In case that's

Peter O'Toole (00:43:04):
Missed there've no on

Wah Chiu (00:43:05):
It. Yeah. That was a one that that was a farewell dinner after the wedding after. Well, the thing is just, we arranged such a way that one, we call it in Northern California and then with a wedding event. And that was a brunch before we all part. And so that's, we gather everybody, it was another nice restaurant in Emeryville right next to Berkeley by the, by the bay. And they say, we are nice Chinese restaurant. So we taking picture in front of that, so that all the, all the two daughters and their six grandkids, their husbands, and then also my wife sisters, and, and nieces and their family as well. So that's one great, fantastic event that day. So.

Peter O'Toole (00:43:56):
Okay. So, so you were originally from Hong Kong?

Wah Chiu (00:43:59):

Peter O'Toole (00:44:00):
Went over to the states, stayed in the states done lots of visit. We might, might get time to have a look at where you've been visiting, but outta choice, where would you live? Hong Kong USA

Wah Chiu (00:44:13):

Peter O'Toole (00:44:15):
Okay. So I'm going to go through some quick, quick buy questions. You an early bird or night owl.

Wah Chiu (00:44:24):
Depends on the days I sometimes get up at six and, and then I often have a zoom call at seven because I still have collaborators around the globe. Mm-Hmm lastly, I have a conference course at 8:00 PM because one of my former post doc, former student now is a professor in, in North Korea. We work in one of the really exciting paper. So, so that would be his morning. So we start from eight to nine and tonight I'm going to have a call at 9:30 PM with a colleague in Singapore. And because I have another colleague in Sweden and who's an editor of a journal and we try to put some special events in, I call computational biophysics mm-hmm with my colleague in Sweden and my other younger colleagues in Singapore. So as a result, depends on the day I could, it could go either way, but I sleep in between

Peter O'Toole (00:45:29):
And hasn't zoom made things easier on that front. The one good thing about lockdowns, I think we've embraced it far more than we had before. I I've got a call. I think someone from Singapore and Australia on wed, Wednesday morning, couple days. Yeah. And yeah, we've all found a time zone that we could all be sensibly awake. But yeah, early morning, late evening, Singapore got off lightly, I think, on this one. So it's,

Wah Chiu (00:46:00):
I agree, but I actually personally did zoom way before the pandemic. So that was part of my thing, because I actually have two offices at Stanford, one on campus and another slack accelerator. And right now I'm sitting in my office in the slack accelerator laboratory, but I also have lab and office down on campus. So, you know, at any one time depends on the day. Like, like today I have to go down in the afternoon on campus when a symposium for undergraduate presentation. So I'll be down on campus this afternoon. So I zoom in between.

Peter O'Toole (00:46:44):
So ask you that's the early bird night owl question? Mac or PC

Wah Chiu (00:46:50):

Peter O'Toole (00:46:52):
Okay. Mcdonald's or burger king.

Wah Chiu (00:46:55):

Peter O'Toole (00:46:56):
I knew that was gonna be the answer. That's easy. if you were to go to a conference what would be the, I, they take your invited speaker, they take you out for food. What would be the best thing that they could actually serve in front of you to eat? What's your favorite food?

Wah Chiu (00:47:12):
Well, I'm actually quite easy. As long as the food is good, it can be any food for any, any kinds of cooking. It could be Italian, French, American, and Spanish, and Japanese, Chinese. Okay. So the only thing I don't yet can haven't yet find an exciting view is an English dinner. I have, I, I love the English breakfast, but I yet, you know, because when I'm Cambridge, you know, Richard used to take me to the college, you know, that was good. You know, you know, where gone to have dinner and, you know, I belong a member of the K horse. I enjoy that, that fellowship, but I haven't really, I know there's some really good English pub, but I haven't really know where to go to find it. Maybe I look you up next time when I come. Okay.

Peter O'Toole (00:48:12):
So, so reciprocate the offer where next time you are up in the UK, come to York and will take your, we'll take you a few places. So I can at least get one that will be right.

Wah Chiu (00:48:21):
Okay. Just to get, you know, trim me. Right?

Peter O'Toole (00:48:24):
Yeah. So we'll definitely try that and I'll make sure Lucy Collins down London also knows it. And the challenge is laid while whenever you're in the UK, whoever's hosting, you has to find you some good. It does exist. It really does exist. So what

Wah Chiu (00:48:40):
I know, I know it does exist. Yeah. So but anyway, I just need to be having some guidance.

Peter O'Toole (00:48:49):
Yeah. So coffee or tea,

Wah Chiu (00:48:52):

Peter O'Toole (00:48:54):
Wine or beer

Wah Chiu (00:48:56):
No, because I don't have these alcohol H nasal enzyme, Mimi.

Peter O'Toole (00:49:02):
So neither chocolate or cheese.

Wah Chiu (00:49:06):
I don't like chocolate, but I would, I would take cheese.

Peter O'Toole (00:49:09):
Okay. Book or TV.

Wah Chiu (00:49:14):

Peter O'Toole (00:49:14):
I, I was gonna say you can't, can you, because you're working 24 7, how are you gonna read a book or watch TV? I've gotta say, I've never really got into reading books because you can be reading science. It, it, yeah.

Wah Chiu (00:49:27):
Yeah. The reason is my eyesight is no good. So I always need magnify who, you know who the Mac, right. So it is always digital. So it's but I, I start printing and try to look at it, but it's very stressful to my eye. And you know, all the, all the transatlantic fights, I, I always work. I never watch any movie on the long flight. I find it very productive to work on a paper or grant proposal during the long flight. I, I was very productive.

Peter O'Toole (00:50:01):
I gotta say I, I would I think train journeys in the UK are great for grant reviewing grant writing, peer reviewing so forth. I think long haul flights. Now, long flights are a great place for a movie. It's it's one of the few times you actually get to stop and you, you, I'm a captive audience and I'm ver rarely a captive audience. There's always, even at home, I'll get up and move around there. I'm kind of, of stuck. So I quite like watching a movie on a plane. So you don't have a favourite film.

Wah Chiu (00:50:33):
No, I don't. I don't watch movie. No.

Peter O'Toole (00:50:36):
Oh, well that bang goes that question.

Wah Chiu (00:50:39):
I'm very boring. I'm a boring guy.

Peter O'Toole (00:50:43):
Well, that's not true because that, if I look at some of the other photos, you've got friends all around the world and you have visited on sabbaticals people all over the world. So I, where are you in these pictures?

Wah Chiu (00:50:59):
It was, it was in Houston, in a Robert Welch foundation conferences and it's a, it is a chemistry foundation. They fund research only for the Texans. And every year they host a, a very laborious elaborate conferences in that year. That was a conference that Richard turned out to be there. And Jennifer [inaudible] was there as well. So you asked me for pictures and I didn't realize even I had that picture. I started looking at my cell phone so yesterday I looked for it. I said, God, these are nice pictures. That's why I shared it.

Peter O'Toole (00:51:43):
So on this one, where are you here?

Wah Chiu (00:51:48):
We were Shanghai believe or not. So the, the one on your right is supermanium used to be ni now he's in British Columbia. He spent some time with Richard when he was a postdoc. And then on the right, I think is one of the rooms in Kingston. The, the, the MDB the yeah, right. Is, is the the UK the, the, the, the European Bio informatic Institute, not very far from Cambridge. So we have in Shanghai, we have a, we have a workshop and that was in the restaurant. We afterward, we took a picture, you know, it's beautiful high rise in the background and on the right with all these scholarly, kingly looking environment, we, we thought about the validations of the Cryo EM structure. So I have been very active in thinking about procedure, the validate the correctness of Cryo EM structures.

Peter O'Toole (00:53:00):
But you visited extensively for Saudi, Singapore, Japan UK Germany, I think as well. Yes. Yes. Do you like traveling?

Wah Chiu (00:53:14):
I used to like it, but now it's a hassle traveling in my last trip to Europe. I spent, I spent five city in 15 days. That was, I never traveled like that when I fought back, but it was difficult, but but I think I enjoy talking to various people. I spend some time at Oxford and at diamond and Cambridge and London. So I, and then also in Netherland, I stopped by three different city in Netherland and I visit Thermo Fisher in Czech Republic. So those are very scientifically, very productive trip. So yeah, I, I think I learn a lot through the interactions. That's correct.

Peter O'Toole (00:53:59):
Yeah. And, and I think, so you, you're saying how you, you are learning as you're going on these events, but you also do a lot of not just undergraduate teaching or teaching. You also run a lot of courses as well. And you sent me some pictures of, I presume courses based around the cryo electron microscopy.

Wah Chiu (00:54:17):
Right, right.

Peter O'Toole (00:54:19):
And not just physical. So this is, I presume it's Stanford

Wah Chiu (00:54:22):
That's right. That was, these picture would, were events before the pandemics. And so we went free workshop a year before the pandemic. And so people could come in to, to learn. And the speakers, the top one is director rose, who is the grandfather of image processing. And then, and then the one in the bottom is José María Carazo from Spain. And then with one of the G L manager in America. So these are taking place in Stanford and the other with the, the in person attendance, we always had zoom even before the pandemic, people can log on for that. Now that's exciting. This one these are all my European colleagues from CCP four experts that they do modeling. So we have them the whole three days workshop in Stanford. I think we are more than 300 participant why they were teaching me Bo. They were very successful.

Peter O'Toole (00:55:31):
Yeah. And, and I, you sent another picture, more people, but I, I, yeah.

Wah Chiu (00:55:34):
Right. Those are the audience, you know, the snapshot. Yeah. I notice. Right, right, right. When you saw that these are the speakers, many of them are, are from England.

Peter O'Toole (00:55:46):
So you just need to come over here and run a course. We'll do it, the Royal Microscopical society and set one up,

Wah Chiu (00:55:51):
I'd be happy to, I'd be happy to

Peter O'Toole (00:55:55):
Structural Cryo em, and we have courses, but the RMS actually, I, I noticed some of your early works and not, not so not. So, so even more recent ones you're published in the journal, the microscopy as well multiple times. And so actually wearing my Royal microscopical soci society hat. I should just point out that some of those publications are published in there and the authors and co-authors on it are huge names in their, their own rights now as well. And it's great that you supported a journal that is run by a charity for microscopy and publishing your work in there. So I thought that was so it's just, I'm wearing another hat at that point from the RMS. But I, I thought that was really cool actually to see on those. Yeah.

Wah Chiu (00:56:42):
Well, I'm, we may, I mean, we actually writing some paper, the audience here on microscopies, we, we will consider that. I mean, because in the old day that was the only journal when I was a student in those days. I think now the American microscopy and microanalysis have their own journal, but but I always thought the journal microscopy as a very incredible group of, of editors and they were knowledgeable. So yeah, I, I would think about that because the next paper I'm, well, we haven't decided where to submit. I mean, we are still in the drawing board, but, you know, I will keep that in mind. Thanks very much for reminding me that opportunity.

Peter O'Toole (00:57:36):
Why, if you submit that, I think Michelle Peckham, who's now chief editor, he's going to owe me a drink and that'll be that'd be very good. But it, it is an excellent journal.

Wah Chiu (00:57:47):
Yeah, no, I agree.

Peter O'Toole (00:57:48):
It's modernizing as well. And you're really stepping forward. The quality of publications in there have gone up markedly. Yeah.

Wah Chiu (00:57:55):
I, I like to ask a question if I may, because I remember I was in one of the meeting is organized by the Royal microscopy some years ago. I couldn't remember. It, it, it took place in London. It was, I remember the event, but I couldn't remember the detail of, of the conference. And I often ask myself how come the Royal society don't put up more of this event or some of the journal as well, because, you know, in the old day, the Royal society proceeding was very prestigious. I remember one of the really classic paper by Aaron Crook and others was in that journal, but I don't see that anymore. I wonder what happened to the activity in your society?

Peter O'Toole (00:58:52):
Yeah, I, I, I could answer that. So I, I dunno which meeting it was in particular down in London, if it was a larger one that would've been microsite micro, which became micro science is now micro it's. It's now MMC microscopy mic Microscience Microscopy micro Congress, which is in Manchester every other year. I see. And, and actually scientifically that's become quite a big program now, cuz it brings in all the physical sciences, material sciences alongside the life sciences. And there's generally six parallels, but you've got all these synergistic and life and materials together. Right. And people can just freely go between them. And I, I find it odd. I, I, I, I walk into a lifestyle, walk into a life science session and I'll see some of my own physicists at York in the same room thinking, I didn't know you were interested in this area. So I learn more about them. And likewise, I'll go to the physics ones and hear what they're talking about, cuz the relevance and what we can learn from each other. So that's every, oh I think beginning of July every other year.

Wah Chiu (01:00:05):
Oh really? Ah, okay.

Peter O'Toole (01:00:07):
So certainly come to it. And the journal, as you say, a lot of journals started to compete which made things thinner way, but the journals really going after quality now and, and it's UPP in its game yeah, it's hard. It's a very competitive market at there and we just need to get the best publishing in what should be the best journal. I think it's, it's our journey. It, it is The Microscopist journal I would argue. Yeah,

Wah Chiu (01:00:36):
No I agree. I agree. Yeah. So I also work with my material science cardiac Stanford in the last two year during the pandemic, we started the, the symposium called E Stanford EDX. And so it's, it's a one and half one and half hour symposium. One top will be given by bio and at the top will be given by material science. So my colleague Bob Sinclair, who used to be from a student in, in Cambridge years ago, but now he's a, a well known professor at Stanford in material science. So he and I put together this series it's actually, he is, but it was really well attended because we try to integrate between the bio and non bio microscopy together. So

Peter O'Toole (01:01:32):
Yeah, I, I, I think it's great. I also like the fact that the exhibition that MMC has all the companies associated with both Uhhuh. Because again, I actually, the exhibition's probably the most exciting bit I can read about the science, right. Actually going around and seeing what the companies have got and companies, I wouldn't usually see to get ideas and new ideas. I it's fantastic. Yeah. I realize we are over the hour mark already and I, I, and I haven't got through all your pictures, but there's one which actually I think is above your shoulder as well. This has to be one of the coolest, wallpapers you can have as a zoom background. This is all your, all the various structures of, I think proteins we've got viruses iron channels, RNA complexes. What an image.

Wah Chiu (01:02:25):
Thank you.

Peter O'Toole (01:02:28):
And again, this is what, 35 years of work.

Wah Chiu (01:02:32):
No, no, this all this work. No, this, all this work was done two years since I moved to Stanford.

Peter O'Toole (01:02:40):
No in 35 years of work has now come together. Yeah. And now it's like a PhD, isn't it? You spend three, four years working and then the last three months, everything pops out.

Wah Chiu (01:02:51):
That's correct. That's correct. That's right. That's right. That's right. This is one

Peter O'Toole (01:02:55):
Of the coolest backgrounds. What we, we are, I'm really sorry up to the hour. So actually everyone who's listened. Thank you very much for listening. Do go see Richards. And some of the other podcasts and Richard Henderson is also utterly brilliant to listen to, and don't forget to subscribe and to whichever various channels, but Wah you are brilliant and thank you so much for taking your time. I, I, I know your time is precious. You work 24 7, but it is great. And I think actually this is a great way. If you are listening to this as an undergraduate and you wondering which lab to go to, to do a PhD, if you're doing a PhD and want to know where to do your postdoc, there you go. I've just done your advertising for you. Go.

Wah Chiu (01:03:35):
I hope so. Yeah. No, I think the fun thing being a professor to have an opportunity in there with the students, I think that's the funnest part of the job. So, you know, because I feel the important thing is to learn from the student through their questions that was inspire my way of thinking how to explain better or to discover. I actually may not understand the thing I thought I understood. Right. So, but so I think the teaching and learning is very important of our life as being an academicians.

Peter O'Toole (01:04:10):
Actually, I, I, I, I know we just finished the podcast. I've gotta ask the question though. Before we close off, do you find sometimes it's a naive of the questions that is enlightening and inspires the next novel idea?

Wah Chiu (01:04:22):
Oh, absolutely. I, I think, you know, a very, very mundane questions at the, at the beginning. I said, oh, what a stupid question, but when do you think about it? It's not that stupid, you know? And so I, I, I, I I'm really open to the question. I don't think I don't consider any question to be stupid questions, but so I, I, I do enjoy the, the interaction with, with either the student or colleagues to, to have these kinds of conversations. That was a part of the fun of the job.

Peter O'Toole (01:05:01):
That's a good note to leave it on. There's never a, there really isn't ever a daft question. It could be the daft question. That is the next big thing that comes out. So again, while, and everyone who's watching this and thank you very much.

Wah Chiu (01:05:14):
Okay. Thank you. I look forward to the English. Good dinner. When I see you next,

Peter O'Toole (01:05:19):
I look forward to finding it for you.

Wah Chiu (01:05:22):
Okay. Good. All right. Bye-Bye

Intro/Outro (01:05:24):
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

Creators and Guests

Wah Chiu (Stanford University)