JUR: Could you give us a quick background on your research?
Dr. Welte: I am a cell and developmental biologist using fruit flies (Drosophila). Most of my work these days is on the role of lipid droplets in animal development. Lipid droplets are cellular organelles used for fat storage – discovered by the same person who discovered mitochondria in the late 1800s. However, there were no serious cell-biological or molecular studies on them for the next 100 years and work really started in the 1990s. [Lipid droplets] turn out to affect lots of cellular processes, and there’s still lots being discovered.
JUR: How did you first get interested in lipid droplets?
Dr. Welte: I had been a graduate student working on Drosophila development, and then I did a postdoc with Professor Eric Wieschaus at Princeton, who happened to have a side project on lipid droplets. Very few people were studying them at the time, but I was fascinated. What he had found is that they relocalize during certain stages of embryo development in flies, slowly drifting inward from the periphery towards the center. Using real-time imaging, I discovered that they rapidly move back-and-forth along microtubules and that this motion is temporally regulated. In collaboration with biophysicist Steven Gross, we also figured out how to measure the force with which they move. I knew very little about lipid droplets themselves, in part because hardly anybody did. It was the time when the field as a whole got started. I was lucky to get into the field early, and the field sort of grew up around me, so that I could witness and participate in major breakthroughs.
JUR: In such exploratory work, how did you decide what projects to pursue and what strings to pull on?
Dr. Welte: Many of the directions I went into over the years were simply because there was a mystery to be solved, and I’m attracted to solving puzzles – especially if it’s a very open puzzle where we don’t know much yet. Along the way, we made chance observations that turned the research in a whole new direction. So, when we were studying how lipid droplets move inside cells, one approach we decided on was to purify the lipid droplets biochemically – to see what proteins are on them. I had expected we may find around 12 proteins, some of them would be microtubule motors and the others would be the motor regulators that we were interested in. But instead, there were hundreds of proteins on there. Interestingly, some of the most common proteins were histones, the proteins that package DNA in the cell nucleus, which didn’t make any sense at the time, but that puzzle really interested me. So, we started doing research where we first figured out how the histones are attached to the lipid droplets, and then that led us into what the function of the histones were.
JUR: Over the past few years, publishing has gotten more important, and a publish-or-perish mentality has become dominant in the scientific field. How has this changed the way you do research, and how do you balance this against exploring what you find exciting?
Dr. Welte: I do feel the need to publish, so that I can get grants and keep my research program going, in part because it’s not just about me, it’s about my students and other lab personnel that need to be paid. It is certainly true that I go after the things that I find exciting. When you write grants, as long as you can convince other people that it’s exciting, and that you can do the work, you will be able to get the funding. Some of those bigger ideas excite people, so to get funding you need to show that things are feasible, but also that they are interesting. I go after some things that are more mysterious, and that excites people more, so that’s just one way to run a research program.
JUR: In the research process, when do you decide that your research has reached an appropriate conclusion to publish, given that each new finding opens up so many more questions?
Dr. Welte: That is always a difficult question to answer for any project, and certainly for graduate students, since they need have published to advance in their career, to get postdoctoral positions and their own grants. There is certainly a pressure to conform to the schedule of normal graduation, so students don’t spend too much time in the lab, but I generally want my students to have complete stories that they publish. There are two general ways to do that – just putting more work into answering the original question, or to step back and see if the data already tell us something that’s worth reporting. Often, especially with students, I found when they have a project outlined, they at least initially stick to the original idea we have and try to fill that in. I think that it’s an easy frame of mind to fall into, and I do that too, but especially when you’re forced by external circumstances, you can step back, look at the same data and find – oh – actually this tells us something new that we just hadn’t appreciated. And then, you can wrap up a story in a completely different way than you had initially intended. So, stepping back occasionally from your data, and reimagining what they already tell you, I think is really important. In the natural life cycle of science, that happens whenever you have to present your work, as a poster, as a talk. You are forced to think about it more deeply, and as a result you often find new ideas that you simply didn’t take the time to develop without the external pressure to present.
JUR: How do you prepare your students to present their work, and how do you promote them to see it as an opportunity to refine their work?
Dr. Welte: In our weekly lab meetings, people present all the time, and so then there is less pressure because it’s a friendly group – so there will be less anxiety involved in the presentation. Whenever somebody gives a presentation outside the lab, we do practice talks in the lab, and then everybody gives feedback on the talk, which is helpful for the presenter, but also just for the listener, because they learn how people give feedback and what sort of things they focus on. Often in these practice talks, we come up with ideas as a group that completely restructure the original talk, and so people get used to the idea that you have to revise your thinking all the time.
JUR: How do you manage to take your research and bundle it into a clear and coherent narrative?
Dr. Welte: One of the most impactful courses I took as a graduate student was a scientific writing course. I still use examples or guidelines I learned there to tell my students how to structure papers; having a good understanding of how English writing works in general, has been really beneficial for me for knowing how to structure arguments. I guess the other important thing is … that you have to be able to step back from what you’ve done, and potentially rearrange it. The first time or maybe the 10th time you develop an argument, it may not be the best, and many times when I’ve written papers the order of paragraphs has changed many times. When I look at the draft with fresh eyes, there are lots of new thoughts emerging, and I realize telling the story going from C to A to B is better than A to B to C. Thus, being willing to go over what you’ve already done and look at it from a new perspective, that is very important. However, it takes lots and lots of time, but it is time well spent.
JUR: When do you decide to stop revising and be happy with the writing you have produced?
Dr. Welte: I think that’s a difficult step for me to take. Often when you write papers you also give talks about them, and you see or experience how the audience reacts: what they understand, what messages they take away, and once you feel like it comes across the way you planned, then you realize you can probably stop.
JUR: How do you promote collaboration in your lab?
Dr. Welte: In my lab, projects typically do not overlap very much, which helps prevent competition. That also means that people typically are completely in charge of their projects and develop them on their own. So, it’s not that we all work on one big project together – it’s more a number of individuals that are sort of in parallel finding their own path, but then we talk to each other. Often techniques or ideas that somebody else has turn out to be applicable for another person, and in part because there is no competition people feel freer to share their ideas.
JUR: What roles do undergraduates play in these research projects?
Dr. Welte: Over the years, so many different undergraduates were involved in research projects, by now over sixty. Often, they start out with very simple tasks in the lab: they learn techniques, they learn how to perform, think about, and plan experiments. I often let them explore their own ideas – one undergraduate started centrifuging embryos, that is one of the things we do to separate lipid droplets from the rest of the cell. He discovered something in one of the mutants that we had never seen before. Then, [he] worked with a graduate student that led to an entirely new project, and he sort of developed part of that project on its own. His findings became part of a published paper, with him as a co-author.
JUR: Undergraduates face greater constraints in terms of the time they can commit to research, what kinds of questions do you recommend undergraduates to pursue to maximize their time?
Dr. Welte: Try to find a question that excites you, but that’s feasible to do; I guess that’s true at every level. There are really big questions that might take decades to answer; I’m not sure that can motivate you day-to-day. In conversation with the people in the lab or with your PI, find a question that has a bigger implication but that seems like it could potentially make a dent, but also something which you can enjoy day-to-day.
JUR: Who were some of your mentors, and how did they support your exploration of science?
Dr. Welte: The two mentors that affected me the most were my graduate (Ph.D.) advisor, and my postdoc advisor. My graduate advisor was Professor Susan Lindquist, and I think I learned from her very rigorous thinking and careful systematic analysis. She also, once I got started in the lab, gave me lots of intellectual freedom. She would set me up with a postdoc, to learn the techniques. Then once I could start exploring, she let me explore and try out my own science, while giving advice to steer me in certain directions when needed, but otherwise let me run with my ideas which was very freeing. My postdoc mentor Eric Wieschaus was similar in this regard, but one of the things that is especially important for me is that he is just extremely excited about science. He will talk to you as a peer if you’re an undergraduate or a full professor, and even though he won the Nobel Prize it didn’t seem to affect how he relates to people – he still talks to everybody. Really, as long as the science is exciting, he will be excited. I guess both of these appraoches I have tried to bring to the mentoring of my undergraduates – to get them excited about science and be excited about it when they bring thoughts to me.
JUR: Can you talk more on your experience as a PhD student, and what do you think could have improved?
Dr. Welte: It’s been a while, and I’m sure I have romanticized it in my mind. I really enjoyed being a graduate student; I liked the freedom to explore without any real responsibilities besides my own science, and I had very supportive lab mates. What I would change … I’ve been really anxious all my life, and I wish I had reached out for mental health support earlier in my career. Especially at the time, it was still looked down upon; people didn’t really talk about mental health issues very much, and it was pushed under the rug. So, if I knew about therapy and that it was accessible early on, I could have dealt with some of my anxieties much earlier, anxieties that I just have from how my personality is set up, but that also get amplified with a high stress job.
JUR: Do you have any advice on how to deal with experiments failing, how do you mentally cope with that?
Dr. Welte: There are two things there. First, especially once you’ve had your first success after a few failed experiments, you might feel … that success outweighs all the failures before. You learn, that’s just part of how science works – that you have to go through many failures to get occasional success, and if that success … is enjoyable, that can make up for the many failures. The other thing is, if you enjoy the process itself – in my case the fact that I love looking at fruit fly embryos – that can make up for a lot. Thus, even if a particular experiment didn’t give you the embryo staining pattern you hoped for, you still get to do something that you enjoy: seeing these beautiful embryos under the microscope. So psychological you still get something out of it, which can help you deal … with that disappointment.
Drosophilla embryos stained for F-Actin (phalloidin) in white, and DNA (Hoechst) in cyan.
Obtained from: Michelle S. Giedt, Jonathon M. Thomalla, Roger P. White, Matthew R. Johnson, Zon Weng Lai, Tina L. Tootle, Michael A. Welte, Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets, Development, 2023, Fig. 1.
JUR: What was your path to PhD, what were the factors contributing to your decision to pursue one?
Dr. Welte: It is probably a very unusual usual path. I was an undergraduate in Germany, which at the time was a very rigid system, and at the university I was in, there wasn’t a clear path for undergraduates to participate in research.There were a few that somehow get involved, but I had no idea how you could manage that. I ended up spending a year abroad during university in Seattle, Washington, and I didn’t need the courses that I was taking there for my degree. So, it was a year for me to explore. I took a few courses that I was interested in, but I also got to work in a lab, and that changed my trajectory. Until that time, I had an equal interest in biology and mathematics, I was a double major, and to some extent I liked math more because I got to apply it to solving problems on my own, while in biology you just did precooked experiments in lab courses and it didn’t really matter if they worked or not. So, for nine months I got to do research at the bench and actually made a little bit of progress – after that I took one more math class and decided, although I still liked it, it was too far from things that mattered to me, and at that point I knew I wanted to go to graduate school in biology.
JUR: From your Ph.D. to your current work, you have been working extensively with the Drosophila (fruit fly) model. How do you keep staying interested in this model organism?
Dr. Welte: There are so many questions that you can address, and there are very strong tools to address basic biological questions with this model. Over the years I’ve broadened my perspective from the embryo to other life stages, so that keeps things fresh. But in part what makes this model organism so great is that we already know so much about its biology. For example, when it comes to early Drosophila development, there’s so much understood already; when you add a new component, like lipid droplets, there is a huge context for figuring out what it might mean when you observe something new, like the effect of mutations in a lipid-droplet protein. Also, I just love looking at fly embryos. I used to say … and it is still true … when I have a bad day in the office, I go to the lab and look at embryos and I find my happy place. There are just certain things that appeal to one in one’s research because of their aesthetics or that you like not for any particular scientific reason, but just because it appeals to you in some other way. I’m very visual, I like looking at images, and embryos in my mind are simple enough that I can fool myself into thinking I could completely understand them eventually, but complex enough that there are lots of interesting things going on there that can still be explored.
JUR: Do you believe that your publication of many thorough literature reviews in your early career helped you get a better sense of the field?
Dr. Welte: It definitely helped me to wrap my head around the big picture – what sort of patterns I see in the literature, and how to articulate them. Mainly because I had to read a lot of original articles that broadened my own view, but also because I did it mostly on my own. I could develop my own thoughts and ideas – some a little bit speculative and maybe a little bit out there – but I could because I was the only author. I could take the risk and had the freedom, and some of them (those ideas), I think, inspired the field.
JUR: Your work is quite interdisciplinary, when you talk with other scientists in these fields, in conferences and such, how do you not feel like the odd man out?
Dr. Welte: There are lots of cell development biologists that study flies, there are some conferences where I fit right in, and for other conferences … like for lipid droplet conferences, I definitely felt like an odd man out for a while, but that means I can bring a new perspective, and people tend to be interested in something not completely mainstream. You also then learn a lot about the rest of the field that might inspire your own research. For example, even though I’ve studied lipid droplets since 1994, I didn’t focus on the lipid aspect of the lipid droplets until maybe starting ten years ago. I had studied the motion of lipid droplets and how they interact with proteins. But I’ve gone to lipid droplet conferences since 2007 and learned a lot about lipid metabolism from just listening to talks and looking at posters. Now I’m applying that knowledge to ovary development, and we are finding new aspects of lipid metabolism in ovaries, an area that got very little attention previously, especially not when it comes to a role for lipid droplets.
JUR: You also teach a course, Advanced Cell Biology, how do you improve the research abilities of the students in your course?
Dr. Welte: So, in this course I teach … my goal is for the students to learn professional skills in science and learn how to analyze papers critically. One big aspect of the course is that the students write a research proposal by the end of the semester, and because most students have never done that before, we do that in steps. They first write an outline, just one or two paragraphs, and I give them feedback on that. Then they write the long outline of that draft, and after that multiple additional drafts. After each step, they get feedback either from me or from a peer, so students gradually get used to all the elements that go into writing a proposal.
JUR: How has being a member of the LGBTQ community affected your scientific career?
Dr. Welte: I came out to myself as a gay man in my twenties and was lucky that the Ph.D. and postdoc labs I worked in were supportive and accepting. Over time, I met a few members of the LGBTQ community that were at the same career stage. Unfortunately, that was not always under positive circumstances: One of my gay classmates in graduate school was assaulted and beaten up on his way home from the lab one night, with the attackers shouting homophobic slurs. But for a long time, I never knew of a member of the community that was further ahead in their career and who could serve as a role model. Clearly, there must have been queer faculty out there, but I didn’t know how to recognize them. Without such representation, it is easy to feel alone and to question one’s ability to succeed in science. One of the things I now spend a lot of time thinking about is how to increase the visibility of LGBTQ folks in science, at UR and beyond. Such visibility is not only important for other members of the LGBTQ community; role models and feeling represented can make a huge difference. But it is also necessary for science and society at large, so that they realize that LGBTQ scientists are everywhere and make important contributions to research and teaching.
Lightning Round
JUR: What is your favorite color?
Dr. Welte: I don’t know; I like a lot of colors. I wouldn’t want to choose [one of] them – I like the rainbow.
JUR: What is your favorite kind of microscopy, to look at, and/or to use?
Dr. Welte: We use scanning confocal microscopy for many of the things that we are studying, as it is a good workhorse. I’m involved with a group that is developing a new light sheet microscope, working with optics, data science, and BME, so that will open many new avenues of looking at embryos and other things. So, in some way I like the microscopy that answers the questions I have at the moment.
JUR: What is your favorite type of cell?
Dr. Welte: Another question where I would rather not have to choose. Well, technically, early embryos are a single cell, and I love studying this stage of embryogenesis. Other than that, maybe nurse cells during oogenesis; those are the cells that help the oocyte grow. They make thousands of lipid droplets, and then transfer them to the oocyte. They are big and have a lot going on, and we have many tools to visualize the processes in them.
JUR: If you could give immortality to three living scientists, who would you give immortality to?
Dr. Welte: I don’t know. Probably at least one of them would be my postdoc advisor, because he’s just a fun person to talk to. He is brilliant, he’s also a little crazy, but he’s also a wonderful person. He is a lateral thinker; he thinks differently than other people and sees connections where nobody else has previously noticed them.
JUR: What books are you currently reading?
Dr. Welte: I’m currently reading three different books and listening to a podcast. I’m reading a book entitled “Human Errors” which talks about the ways in which the human body is not well designed. This idea that evolution did just enough to make an organism work, but that is doesn’t come up with a perfect solution. In biology, we typically view organisms and cells as being really well adapted and perfect. That is true in many ways, but evolution doesn’t necessarily select for perfection, it just has to be good enough. One favorite example is that rabbits eat their own feces to … get Vitamin B12. It doesn’t seem like a well-designed setup, but that’s how it works since the bacteria that produced the B12 live in a region of the gut after where the transport proteins for the B12 vitamin are. So, rabbits have evolved this behavior that they eat their own feces, so that they can get the B12; it works, it’s probably not an elegant solution, but it works. The book mostly focuses on the human body, but then also talks about some other mammals’ evolutionary solutions that seem really inelegant, or don’t really work that well, … it’s a refreshing perspective to entertain.
I’m also listening to an audio book on the history of Christianity. I’m really interested in … the history of philosophical thought, and because of that in the development of religious thought. I’m also reading a book called “Global Crisis”; it’s the history of the 17th century, when there was a lot of climate change, including the little Ice Age, which affected temperatures globally. So, this historian looks at the collapse of various societies around the world from China to Europe to Africa; lots of societies had major wars or major upheavals that he tries to tie to climate change … I find it really fascinating.
JUR: Why did you grow out the beard?
Dr. Welte: I started to grow it out when I became department chair, and I haven’t shaved it since. I was department chair for two three-year terms, and that’s when I started growing it. I’m not quite sure how it’s connected, but in time it’s connected, and … I’ve grown fond of it.