Chapter 05: Training a Researcher’s Mind: Ph.D. Research
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Description
In this chapter, Dr. Bogler talks about his process of selecting his PhD program.
First, to explain how his intellect was being trained during college, he explains a college research project for which he studied 2-D proteomic gels, leading to his fascination with cell differentiation. He notes that this was a cutting edge topic at the time.
Next, Dr. Bogler explains the English system for selecting a PhD program: a student selected a laboratory to work with, not a school. He ended up at the Ludwig Institute for Cancer Research in a neuro-laboratory focused on the study of oligodendrocyte precursor cells (’88 – ’91). Dr. Bogler explains some administrative issues that arose with his degree from this institution. He also notes that work at this cancer institute did not fire his interest specifically in cancer at this time.
He explains his research, then his move to the Salk Institute for a post-doctoral program (’92 – ’93), noting that he learned a lot of molecular biology. He explains why some departmental tension held back his research.
Next, Dr. Bogler explains that at the time, the Ludwig Institute was opening new branches, one eventually in San Diego where he did his second post-doctoral fellowship (and also met his wife, Irene Newshaw). His cancer-focused work began at that time with research on the effects of the p53 gene on astrocytes.
Dr. Bogler also notes that some groundwork for his administrative perspective was established during this time. He explains that in becoming proficient at bench work, a laboratory researcher also comes to understand that there are limits to the type of work he can accomplish alone. This drives a researcher to collaboration and established his own commitment to a collaborative perspective.
Identifier
BoglerO_01_20141110_C05
Publication Date
11-17-2014
Publisher
The Historical Resources Center, Research Medical Library, The University of Texas Cancer Center
City
Houston, Texas
Interview Session
Oliver Bogler, PhD, Oral History Interview, November 10, 2014
Keywords
Professional Path; The Researcher; Professional Path; Personal Background; Influences from People and Life Experiences; Overview; Definitions, Explanations, Translations
Topics Covered
The Interview Subject's Story - Professional Path; The Researcher; Professional Path; Personal Background; Influences from People and Life Experiences; Overview; Definitions, Explanations, Translations
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Disciplines
History of Science, Technology, and Medicine | Oncology | Oral History
Transcript
Tacey Ann Rosolowski, PhD:
I’m not quite sure how to ask this question, but, you know, during any kind of graduate program, I mean intense program like a PhD program, I mean, your brain gets shaped in some pretty interesting ways. How was your mental instrument getting formed at that point? Did you sort of discover “I’ve got a style of looking at questions,” or, “This is a particular type of question I’m interested in,” or method, intellectual method, you know?
Oliver Bogler, PhD:
Yeah, I think I did. So we were given an opportunity to do a project. We had to do a project as part of our third year as we were coming up to our finals. I was interested in screens, so there was a lab that I chose to do this eight-week project and I was accepted into it. They were doing 2-D gels, the first sort of 2-D proteomic gels, try and compare the protein pattern in cells after being stimulated with a particular thing. The lab was focused on a protein called protein kinase C, which was actually a family of kinases, and we were hitting it with this phorbol ester called TPA, in which you just switched on amazing amounts of stuff in there, and we were looking at the phosphorylation, so it was a highly radioactive experiment. I wasn’t doing this unsupervised. I was working with a more senior member of the lab. The idea was that you would do a pattern, you would generate a pattern, you would do comparisons, and so that’s something that I was drawn to. I didn’t come back to that until sometime later, and actually the last few years in my lab we did some phosphoproteomics with much different technology to essentially answer similar questions. But the thing I really learned, the thing I really got excited about was cellular differentiation, and that’s what led me on my next step. So I was just fascinated by the way the cells make choices and change function and become specialized. I thought that was really, really interesting, and at the time was not very well understood or very well determined. And part of one of the—I forget. I think this was in my second year, we were getting taught by some of the developmental biologists at Cambridge, and there were really great people there, John Gurdon and just some amazing, smart people. That wasn’t the focus of what I was doing, so I can’t quite remember how I got—I think there was some crossover in the lectures, but I forget exactly how that was structured. But there was just a lot of interesting and exciting work going on at the time with how the body plan was developed and how cells knew where they were and then, from that, knew what they would become and how they would become that. So this became really interesting to me, particularly at the cellular, not so much at the organismal level, and when it came time for me to look for a PhD position, which is done, I think, done very differently in the U.K. than it is here, again, you don’t really apply to a graduate school. You apply to a lab. You find a professor that you want to work with. And because, as I said earlier, there’s no didactic component anymore, you just go in the lab for three years and you write a thesis and you hope for the best. You kind of pick a lab. And so I was picking labs, and there are certain application processes, and I was reading the journals and applying to things. I had two labs that I really was interested in, one of which was up in Manchester, and they were focused on hematopoiesis, which I thought was really interesting, because the blood system at that point was the most well-developed differentiation system that there was. We knew quite a lot about the white blood cells and the red blood cells and the different trees and everything. Unfortunately, the PhD project was heavy biochemistry and chemistry. They wanted someone to sequence sugars, which was important to understanding it, but it wasn’t what I wanted to do, so I was a little disappointed, and I think that was probably a wise choice. So I ended up in a lab that was focused on brain cells, and was headed up by a fellow named Mark Noble. Mark had done this really elegant work with Martin Raff at University College London, and Raff was a very famous scientist and also wrote one of the textbooks that we’d all learned from. He was a very prominent fellow. And what Mark and Martin had done is they’d worked on these oligodendrocyte precursor cells and they had this amazing experiment. This is what sold me on going to Mark’s lab, which is that they had discovered that in the optic nerve, which is part of the central nervous system and is myelinated, the first myelination in the rat happens at birth, and that’s when the first oligodendrocyte precursors become oligodendrocytes and start, you can detect myelin protein and myelin lipids, actually. What they found is that if they take the cells, the precursor cells, out of the optic nerve four days before birth and put them in culture, if they put nothing in that culture except medium to sustain the cells, they would become oligodendrocytes right away, so immediately differentiate. But if they added one factor, PDGF, platelet-derived growth factor, the cells would wait four days. If it was four days before birth when they took the cells out, they would wait four days to make the first cell [unclear]. If it was two days, they would wait two days. So the cells, just by having this one factor present in the medium, would count the appropriate time and differentiate as if they were still in the animal. It was known as “the clock.” It still fascinates me. We still don’t understand how that thing works, but it was really interesting to me because, wow, how did that work, right? So that hooked me, and when Mark told me that story and I read the papers—they had a Nature paper on this—I think a couple, actually—and I was like, “Okay, all right. This is stuff that I want to get in on.” So I joined his lab and worked a little bit on that area. He was really a cell biologist, cell and developmental biologist, that was his strength, and he brought me into his lab. Actually, another colleague of mine, Andy Groves, who Andy and I had been at Sydney together and had really become good friends in the last year of our time there because we were both doing biochemistry, so we hung out a lot, and we had some other friends we hung out with. Andy and I both went to Mark’s lab, and actually Andy’s now a professor at Baylor. We have obviously separated, but by pure coincidence, he came to Houston about four or five years ago now, and he has a lab at Baylor. So I see him again from time to time.
Tacey Ann Rosolowski, PhD:
It’s a funny, small world.
Oliver Bogler, PhD:
It is a small world. So Andy and I had training in molecular biology, and Mark wanted us to do some of that work, and we did some, but I don’t think it was hugely successful because it’s a bit much to expect a couple of graduate students to really get into that. We did some things, but mostly what Andy and I did was cell biology.
Tacey Ann Rosolowski, PhD:
So tell me more about the PhD and then moving into your first position after that.
Oliver Bogler, PhD:
Yeah, so it took me three years, and obviously I graduated. (laughs) I wrote a couple of papers, I think a few papers, and in the English system, you basically—you work for at least three years, sometimes four, and then when you’re ready, if your professor agrees, you write your thesis up, and you find a couple of other professors and then you have a little committee meeting. I mean, it’s just one committee meeting. There’s no supervision throughout the three years. They read your thesis. And actually, I think, in most places, at least at the time, it was pretty much tradition that you kind of bound your thesis, it’s like you weren’t going to be making a lot of changes, and you gave them a copy. Then we met and they grilled me in the proper manner for an hour or so, and then they said that was good enough, and then that was it.
Tacey Ann Rosolowski, PhD:
It’s a system that really assumes that the student is very self-directed—
Oliver Bogler, PhD:
Right.
Tacey Ann Rosolowski, PhD:
—and did that work for you?
Oliver Bogler, PhD:
It worked really well for me. My experience might have been a little different, so there was a quirk. There’s a quirk in my PhD, which is that I did my PhD at the Ludwig Institute for Cancer Research, what was known—that branch doesn’t exist anymore. The institute is still very healthy and going, but the branch was the Middlesex Hospital branch, and like all the big branches, the branches are built around a director, and then when the director retires or leaves, then the branch typically doesn’t survive. It usually disperses or moves or relocates. So the director of this branch was Mike Waterfield [phonetic]. He was actually a really leader in the [unclear] receptor field and in doing early proteomics and structural stuff, and [unclear] kinase signaling, he made some seminal contributions. Then when he retired, the branch disappeared. But Dr. Waterfield did not want to spend the money to register his graduate students with the University of London. In order to do that, he would have had to pay the University of London bench fees. I don’t know how much the bench fees were. I remember that Mark, my professor, was unhappy with his decision. He felt that the institution do that. But the end decision was that he wasn’t. So they registered us with—and I don’t know how many of us fell into this group; it must be a dozen or a couple of dozen—with something called the Council for National Academic Awards, which sounds desperately like a mail order company. (laughter) So my PhD actually was awarded by the CNAA. So maybe the fact that I was in a fairly unstructured program was for that reason. Maybe if we had been signed up with the University of London, there would have been some committee or supervision or some such thing. I don’t really know.
Tacey Ann Rosolowski, PhD:
Interesting.
Oliver Bogler, PhD:
And of course, to make things worse, the CNAA no longer exists and the records of the CNAA were given to the Open University, which is actually a very historical—and it’s like the first MOOC or open learning platform in the world, and they’ve been around for the longest time. So now if I need a record of my PhD, I have to go to the Open University. But I actually got Dr. Waterfield to write a memo, because I had to explain this every time I changed jobs. (laughs)
Tacey Ann Rosolowski, PhD:
I bet.
Oliver Bogler, PhD:
Because the CNAA, it really looks—I mean, it’s a nice enough certificate, but it doesn’t look like a university. We were not the only ones. If there was a private research institute that had a graduate program, this is where they would register their students. And at the time, you know what? At the time I thought, “This is so unimportant, it doesn’t matter.” But looking back at it from my perspective now, I would have perhaps done things differently. I mean, a trivial and [unclear] when I took the role I am in currently in Academic Affairs now, I’m expected to participate in our graduation ceremonies. So I have to wear robes, not something I’d ever do or thought I would do, right? And the first question was, “Well, what color are your robes?” And I’m like, “Well, the Council for National Academic Awards doesn’t have a color scheme.” (laughs) So I actually wear something fairly nondescript. It certainly indicates I have a PhD in biology, but there’s no university colors because I don’t have university colors. I can’t wear the University of London, because I’m not a graduate of the University of London or any other university or, God forbid, the University of Texas. So I try very hard not to look as if I’m claiming credentials that I don’t have.
Tacey Ann Rosolowski, PhD:
Right. Very, very interesting dilemma. (laughs)
Oliver Bogler, PhD:
I mean, it’s not a big deal, but if I’d known then what I know now, maybe I would have tried to find a way to pay those fees myself or do some other way to get myself signed up for something that has a big more cachet than the CNAA. So there you go. (laughs) That’s my story.
Tacey Ann Rosolowski, PhD:
Mm-hmm, gosh. Quite the dilemma. Now, this was your first—I mean, you were working in a Cancer Institute.
Oliver Bogler, PhD:
I was. I was.
Tacey Ann Rosolowski, PhD:
Was that also coincident with an interest in cancer? Because it doesn’t sound like you were working on cancer [unclear].
Oliver Bogler, PhD:
I wasn’t really, yeah, and so that was interesting. Different parts of the Ludwig Institute had very different approaches, so this branch was very, very basic in its research, and I think the only cancer-related thing that I did was try and make a [unclear] library from a cancer cell line while I was there, which is what I was telling you a little bit about earlier, about Mark’s desire for Andy and me to do molecular biology. So we tried to make these libraries. If I remember correctly, we later on found out that the cell line had been mixed up, and it wasn’t even what we thought it was, so it’s good that the project didn’t go very far. But, yeah, you’re right, I mean, Mark was not directly interested in cancer. He was interested in differentiation, which is fundamental. The work, the core of my graduate work was actually kind of interesting. It did have some cancer relevance. So there was a senior member of the lab who was a clinical fellow doing research, called Damian Wren, and what Damian discovered was that if you take this PDGF molecule, which I was telling you about with the clock, if you add FGF to that and you put both factors in, now the cells never differentiate into oligodendrocytes. They just stay precursor cells forever. So that was Damian’s observation. That was more or less when I joined the lab, so I took over that project, and I worked that up and was the first author on the paper where we published this, and Damian was very generous in letting me be first author. He’d made the discovery, but most of the data in the paper ended up being mine. And then what was interesting was that there was another lab down the road at the Imperial Cancer Research Fund at the time, which no longer exists. It’s a part of Cancer Research U.K. now. But at the ICRF there was a lab there headed up by a fellow named Hartmut Land, a German man, German scientist, and “Huckie,” which is his familiar name, and Mark had been working together on what do oncogenes do to these glial precursor cells. So the parallel was that Huckie’s lab was putting oncogene combinations into various cells and showing that that blocked differentiation, and Mark and I were doing the same thing with just growth factors in the medium. So those were some parallels, so Dr. Land was part of my first paper. Actually, the irony, the cute story is that I was interviewing for graduate work, and I interviewed with Huckie’s lab. I met Mark Nobel for the first time when I was interviewing with Huckie. I met him in Huckie’s office because they were buddies and they saw each other quite a lot, so that’s actually where I first met Mark was in his office. What the Land lab was doing was fantastic, but it wasn’t really what I wanted to do. I wanted to do more cell stuff. They were very gene-based at the time. Both of them, Land and Noble, are now in Rochester together, up in the University of Rochester, so it’s a small world. And I was up there a few years ago visiting them. It wasn’t that cancer-relevant, but there were some cancer echoes. After my graduate work, I did two postdocs. My first postdoc was at the Salk Institute in California, La Jolla, and that was also fairly basic. I’d spent the last year of my graduate work working on a transcription factor that this lab in California had discovered as being important in Schwann cell differentiation. Schwann cells are the myelating cells in the peripheral nervous system, and I was working on the myelating cells in the central nervous system. So we wondered whether the same genes, same transcription factor was—so I was doing some work. Then I went there for a postdoc that was fairly inglorious, I should say, and never really came to much, except I didn’t publish a thing out of those two years, but I learned a tremendous amount of molecular biology at the Salk. So I was in this amazing lab, and it was amazing because of the people that I shared benches with. So there were some really good molecular biologists there, unbelievable people. The Salk at the time was one of the sort of places where these technologies were being developed, and there were some really good people there. So I learned an enormous amount, hands-on stuff, but it didn’t go anywhere for a variety of reasons, mostly because I wasn’t able to establish a good relationship with the head of the lab, and there were some issues there that I won’t dwell on. But the reality of it is that while I was doing this work on his transcription factor in my cells, he was doing essentially exactly the same project with one of our competing labs, which, ironically, was just two miles from us in London. But he never told me about it, and in the end, he decided to publish with them and not with me, but he didn’t tell me that either until I got there, and then I was kind of stuck. So it was a tough situation, and, again, if I had to do that over, I might do it differently. But that was certainly my perspective. He may have a different perspective on it. But long story short, I benefitted tremendously, I learned a lot. And coincidentally, right around this time, another branch of the Ludwig Institute was moving from Montreal to San Diego, and that branch was significant for two reasons. The branch was headed by Web Cavenee, and Web and Mark were friends, and, of course, they were both—I mean, Web was the branch here and Mark was not, he was just a professor in the Ludwig in London, but they knew each other through this Ludwig connection. Web was interested in brain tumors, was actually really interested in brain tumors. Web’s claim to fame—he was many, but his core claim to fame was he was the geneticist who found the retinoblastoma gene, so he really found the first tumor suppressor gene when he was with Ray White in Utah. He was a wunderkind. When I was in Cincinnati, he was just hitting it big when he was in his thirties in his meteoric rise, National Academy member very quickly and all these kinds of things. So then he got this branch of Ludwig and he was up in Montreal for many years, and then I think there were some issues in the Ludwig Institute why they couldn’t have any branches in the U.S., and I think those were then resolved. These were tax issues or legal issues. So Web got a great chance to take his branch to San Diego. So then he and I started talking. Mark put us in touch, and Mark said, “Hey, one of my former graduate students is just across the road from you. He knows about these cells.” So Web invited me over. “Can you show my people how to grow these cells?” So anyway, then when I was kind of done at the Salk, I moved over to Web’s lab. But the other significant thing is that Irene was with Web in Montreal, and he brought her with him when he went to San Diego. So, thank you, Web. (laughter) And that’s where I met her, when I joined the lab, like most good scientists. That’s where I met her.
Tacey Ann Rosolowski, PhD:
So, win-win. (laughs)
Oliver Bogler, PhD:
There you go. There you go. So then I moved into Web’s lab and we started working, so that’s really when my real more sort of cancer-directed work started. This is when some of the first genetic mouse models were coming available. So we worked on astrocytes from mice where the P-53 gene had been knocked out, and studied their biology and did some other things, did some gene identification work and so on. So I was there for probably about three and a half years. So, yeah, those were good years. I mean, Web’s lab was a great place to be, and he’s a super smart guy and knows a lot of things, and I learned a lot from him.
Tacey Ann Rosolowski, PhD:
Well, I feel like we’re leaving a cliffhanger here. (laughs)
Oliver Bogler, PhD:
Okay.
Tacey Ann Rosolowski, PhD:
Because kind of the mission of this particular interview is really to focus on administrative stuff, not on research.
Oliver Bogler, PhD:
Gotcha.
Tacey Ann Rosolowski, PhD:
But the research is really interesting. But if it’s okay, we’ll leave that aside for now.
Oliver Bogler, PhD:
Of course, of course. Please, yes.
Tacey Ann Rosolowski, PhD:
Yeah, I mean, because normally with interviews, I’m like, yeah, let’s power through and talk all about the research and how it evolves, so I’m feeling, oh, my gosh, this is unfamiliar territory for me to quit at this point. But we’ll leave the cliffhanger for the next session. How’s that? (laughs)
Oliver Bogler, PhD:
All right. Fair enough. Fair enough.
Recommended Citation
Rosolowksi, Tacey A. PhD and Bogler, Oliver PhD, "Chapter 05: Training a Researcher’s Mind: Ph.D. Research" (2014). Interview Chapters. 1558.
https://openworks.mdanderson.org/mchv_interviewchapters/1558
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