ABSTRACT

Janet Iwasa pursued her undergraduate degree in biology, with a double major in Asian studies, at Williams College in Williamstown, Massachusetts, USA. She then joined the lab of Dyche Mullins at University of California, San Francisco (USCF) for her PhD in cell biology, studying the dynamics of actin nucleation and filament assembly. Shortly after receiving her graduate degree, Janet also completed a course in 3D animation at the Gnomon School of Visual Effects in Los Angeles, California. In 2006, she moved back to Massachusetts to join the lab of Jack Szostak at Harvard Medical School, in Boston, for her postdoctoral studies, focusing on biological animation. She was a lecturer in molecular visualisation at Harvard Medical School between 2008 and 2012, and then moved to Salt Lake City, Utah, in 2013, where she became an Assistant Research Professor in the Biochemistry Department at the University of Utah. Janet established her own laboratory at the University of Utah in 2018, where she and her group members create and develop molecular and cellular animations for various projects related to molecular and cell biology. In 2014, Janet was named a TED fellow and recognized as one of the ‘100 Leading Global Thinkers’ by Foreign Policy magazine.

Janet Iwasa

What inspired you to become a scientist?

My father is a biophysicist and he worked at the NIH [National Institutes of Health in the USA]. He was my role model. I grew up close to the institute in Maryland and got to spend a lot of time in the lab early on, and it seemed like a fun career. Some of my earliest jobs were interning at the NIH during high school as well as through college. When I was very young, I also wanted to be a veterinarian. But one of the things that I inherited from my father, in addition to an interest in science, was a squeamishness around blood. So I became very uninterested in veterinary medicine, or any medical profession, after that.

You did your PhD in cell biology. How did molecular animation come into play?

It started during graduate school. When I was a graduate student, Dyche Mullins's lab was right next door to Ron Vale's lab [at UCSF] and we had joint group meetings. Dyche's lab was mostly interested in actin, and Ron's lab was studying kinesin at that time. So I watched a lot of group meetings where graduate students and postdocs would talk about kinesin. They presented these figures with triangles as kinesin heads walking along a line, which was supposed to be a microtubule. And that worked pretty well. But when the Vale lab and Ron Milligan's lab solved the partial structure of kinesin, Ron [Vale] decided to hire an animator, Graham Johnson, to depict their hypothesis on how kinesin was walking on microtubules. So the first time I came into contact with animation was when Ron's graduate student presented this during one of our joint group meetings. That was what inspired me to take up animation. It made me realise that this is probably the most intuitive way to understand how molecules work and how dynamic they are. I felt like I never really understood how kinesin worked until I saw that animation. After that, I started looking into animation classes so I could learn how to apply animation to what our lab was studying at the time. I took a course at San Francisco State University. I learned some basic things, like how to make a living room with the walls and the furniture, but then I would go back to the lab and start trying to figure out how to use those same tools to import proteins and move them around.

How was your transition from the wet lab to doing only molecular animation?

I would say that transition was a little tough. When I was in the Mullins lab, I spent one day a week doing animations. I was sitting in front of my computer, but I was surrounded by my lab mates. I was working on animations that had to do with what the lab was studying, so it was very social. And then when I transitioned to my postdoc, I ended up being in a cubicle that was away from the rest of the lab. It was partially for space reasons, and it kind of made sense because I was not doing any wet-lab experiments, but I felt really isolated. It was pretty hard. There was also this sense of professional isolation as well, as I was doing something that not many other people I knew were doing. I didn't have a professional sort of contingent. So that was a two-year postdoc, and I spent a lot of that time going to meetings and trying to engage with different groups to try to figure out where I might fit.

What questions are your lab trying to answer right now?

We work on a lot of different projects, on many different topics, most of which are within the realm of molecular biology. But the general philosophy of the lab is that we're trying to think about how visualisation can help research in terms of communication, and how we can use visualisation to really engage the scientific community, and other communities, to think about molecular processes.

Janet Iwasa with her lab.

Janet Iwasa with her lab.

What do you feel are the main differences in how a cell biology lab and your lab approach a research project?

One of the things that our lab brings is a sort of outsider's perspective. So a lot of the time we're trying to think about context. How is this happening within the context of a cell? What do you need to know to understand this visually? If you're someone who doesn't think about this protein all the time, what do you need to know to understand why this is working the way it's working? We're trying to create a visual narrative about how a protein works, which is more easily done when you're a little further away from the day-to-day research, and also a little bit outside of that field. We're also not thinking about experimental techniques, but more about the bigger picture of what the data tell us. Think of our approach as more like a review article, and a cell biology lab's approach as more like a research article.

“[Molecular animation] humanises the type of research we do by making it more intuitive and engaging.”

How do you feel that molecular animation impacts the field of cell biology?

I think there are a few different ways it does that. In general, I'm interested in thinking about how visualisation can help us ask better research questions. And I think a lot of this has to do with making molecular processes and machinery more intuitive. We can now describe the complexity of processes and proteins in really great detail, so it's getting harder to just draw circles and squares and arrows to describe a process – that no longer really captures a lot of our hypotheses, which are becoming three-dimensional and dynamic. And so our models have to become three-dimensional and dynamic in order to keep up. Visualisation enables us to better understand other people's hypotheses as well as explore our own. We are creating these visualisations at a mesoscale, a scale that's considered invisible to current methods of experimentation. We can capture still images of the proteins' shapes and structures, and we have an idea of how they move dynamically using light microscopy, but to generate a hypothesis of how proteins are moving within the context of a cell requires multiple sources of data. And that's where I think animation is really useful – it provides a visual hypothesis that you can then use to explore an idea and also share it with other people. So that's the bigger part of how I think that molecular animation can impact cell biology.

The second part is about communication more broadly. Animation allows other people to better understand how molecules work. I often liken it to seeing the movie inside a scientist's head. If a scientist has been studying a molecular process for years or decades, they have a movie in their head of how things work that's based on experimental data as well as unpublished work from other people, conversations, conjecture, etc. So they're connecting all of those dots in their heads to create a movie, and the animation process captures that movie and allows other people to see it. And I think that can be really engaging for people, especially those who may not necessarily think about molecular-scale events, such as kids or members of the public. If you just show them circles and squares and arrows, it's hard to get people excited about that. But if you show them a molecular animation of a complex and beautiful process, they can understand why someone might become really interested in that and might spend their entire professional career trying to understand it. So I think in some ways, it humanises the type of research we do by making it more intuitive and engaging.

Do you have a system in place for how you approach each project?

We do. For example, one of the projects we have right now is on coronavirus. So we've reached out to a number of coronavirus researchers to try and get their input and their feedback on the ideas we have for an animation. We have a conversation about how the particular process happens, and then we create a storyboard, which is typically a hand-drawn, step-by-step illustration, as well as a description of what's happening, and sometimes also a narration. That storyboard gets sent to our collaborators for feedback, and we go back and forth to make sure that we have all of the details right. After that, we typically get into the modelling stage where we start creating the protein models, usually at least partially from the Protein Data Bank (PDB), depending on the scale of the animation; we also use predicted structures and model in segments that are flexible or that we don't have data for. We send the models back to the collaborators so we can make sure that we have them right. After that is the animation stage. So we put everything into our animation software, and we start moving things around, thinking about ways of animating the more complex steps. And then we usually go through multiple drafts of animations, sometimes up to 10 or more drafts, that go back and forth between our collaborators and ourselves before we have a close-to-final animation, to which we can add narration, music, labels, things like that, before having that final animation.

Have you had collaborations in which the development of the animation led to changes in the experimental path?

Yes. There have been a few cases. One example is when I was trying to fit together a few different structures that were solved separately. And they didn't fit together. I showed this to my collaborator, who ended up going back to their data. Upon closer examination, they found another class of particles where the complex was in a different conformation that would allow the proteins to fit, and they changed their hypothesis to reflect the requirement for this conformational change.

“You have to learn how to advocate for yourself and for your field.”

What do you look for when you're recruiting new lab members?

Right now, we only have postdocs as full-time members of the lab. We don't take graduate students unless they are co-advised by a lab that's doing more wet-lab research. This is borne out of my own experience – it was really important that I did wet-lab research and had that experience of doing my own experiments. For the postdocs, I'm looking for people who are really pretty committed to doing animation as a career. And they've shown that commitment in one or more ways, for example, by having extensive experience doing three-dimensional animation. If they have none, then I think that's not showing me enough of a commitment. They're also all biologists. Because we focus so heavily on molecular animation, I think it's really important to have a biology background.

What advice would you give to someone who would like to transition into the molecular animation field?

Molecular animation, or anything that is outside of a well-established path, requires you to be your own advocate. You have to learn how to advocate for yourself and for your field. And that takes a certain amount of motivation and certainty that you know you're doing something you love and think is important. I was really convinced that molecular animation was something that cell biology as a field needed, so I advocated for that pretty strongly. I still advocate strongly in my talks that we all should be building better visualisations, and I really believe it.

What do you think were the elements that have been key to your success so far?

Being part of a scientific community has really kept me going. When I was a postdoc, I was in an origins-of-life field, and I was animating things in a topic that was new to me. After my postdoc, I returned to cell biology, and it felt like home. I was so happy to be animating cells and cellular processes again, because cell biology has always been the field that I've gravitated towards. My collaborators and the people who have really supported my career come from the cell biology community. Being part of the ASCB [American Society for Cell Biology] has been a big part of what has allowed my career to work.

What do you think are the next steps to be overcome in the field of molecular animation?

I would love to see the democratisation of animation, or simulations – just any sort of visual modelling of molecules should be something that all researchers should have the capability of doing. And not just specialists. There are really very few other things you can do to better convey your ideas. So integrating it more into our training would be one thing. And just having better tools to enable us to do that.

One of the biggest issues facing molecular animation as a field is how we portray the unknown and the uncertain, competing hypotheses, things like that. So the issue is that if you watch an animation of a molecular process, you don't really know what data contributed to that visualisation, if this is a consensus model that many people in that community support or not, or whether it's kind of a rogue, outsider's view of how this process works. This is something that has been pointed out by members of the scientific community, and I think it's a very valid criticism. We're addressing this in two ways. First, one of the projects that we have right now is thinking about how we annotate our animations to show what data we've used, where these models come from, and why we think that these proteins move in this particular way. And then second, which we're creating as part of the coronavirus project, is thinking about how we use visualisations to better understand the consensus within a community. One of the things I've noticed is that an animation can be really good at getting people to talk about their ideas of how things work, and getting people to understand where they may disagree. We're trying to create a commenting capability where people can view an animation and then comment on it. At that point, from being able to capture this discourse, we as animators can better understand where there is disagreement in the field and possibly make animations that show alternative hypotheses of how things work.

How has your work been affected by the SARS-CoV-2 pandemic?

The projects that we've already started are still going at a pretty good clip, a pretty normal pace. The thing that's hurting us the most is probably my inability to travel and meet people one on one. Most of my collaborations begin from people I've met personally at meetings, or during travel, and that has been seriously curtailed. And there hasn't been a really great solution so far. I think everyone's thinking about how we replace face-to-face meetings, but we haven't come up with the right thing. I think we'll get there, hopefully. But as of this point, I haven't come across any meetings that feel the same to me as being there in person with the same kind of ability to connect with people.

Could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?

I think there are a lot of people who assume that I have an artistic background, but I have none whatsoever. Prior to taking animation classes in grad school, the last art class I had taken was probably in middle school and was required. So I was actually very self-conscious about having to draw anything by hand. I really just don't think of myself as having an artistic bone in my body. [laughs] I still think of animation as being a highly technical skill rather than an artistic one. But the truth of it is aesthetics play a big role in communication. Something has to look visually appealing for people to want to look at it and learn from it. But it is something that I think I've come to terms with. Since going into animation I have become a lot more interested in thinking about art and colour. I would love to take painting classes – I wish I had more time to do that. I like to do woodworking. I've been making furniture – not the best furniture, but it's still sort of usable furniture. [both laugh] I have a lot of saws and things like that. And I also like to bake. I think about things that I can do that are not in front of a computer screen.

Janet Iwasa's contact details: University of Utah, School of Medicine, Department of Biochemistry, 15 N. Medical Drive E, Salt Lake City, Utah 84105, USA.

E-mail: jiwasa@biochem.utah.edu

Janet Iwasa was interviewed by Inês Cristo, Features & Reviews Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.