Sandra Schmid is the Chief Scientific Officer of the Chan Zuckerberg Biohub in San Francisco, USA. She was previously Professor and Chair of the Cell Biology Department at the University of Texas Southwestern Medical Center, and Chair of the Department of Cell Biology at Scripps Research Institute, CA, USA. Sandra's research over the years has focused on the biochemical dissection of the endocytic pathway, in particular the role of dynamin and the mechanisms of clathrin-mediated endocytosis. We chatted to Sandy to find out more about her career, her role as an advocate for women in science, and her recent transition to the Chan Zuckerberg Biohub.

Sandra Schmid

Let's start at the beginning: how and when did you first become interested in science?

My father was a high school science teacher – he actually wrote textbooks that were used for teaching science in grades eight, nine and ten (age 13–15) – so I was exposed to science as early as I can remember. Throughout the year, he'd bring home the pickled fetal pigs that you'd dissect in high school or dry ice to play with, or he'd be taking pictures for the textbooks. So, I guess I was always interested in understanding the biology of what was going on around me.

And how did you then get interested in cell biology in particular?

When I was in school, I decided that I wanted to be a zoologist; I loved animals, so it seemed like the obvious choice. I went to university (at the University of British Columbia) and took virtually all the science classes I could. I had a really terrific biology professor in my first year, Professor Barbara Green, and she opened up the world of cells to me. She showed us beautiful structures that were being revealed by electron microscopy and, by the end of my first year, I decided I wanted to study cell biology. I organized all my courses around that, including cytology, physiology, biochemistry, biophysics, organic chemistry – anything that was crucial for understanding cell biology. Basically, I was able to individualize my program so that I came away with a bachelor's degree in cell biology.

How did you choose what to do and where to go for your PhD?

Well, that's an interesting story and one that I think is relevant to many young women in science. Between my third and fourth years at university, I met and fell in love with a man who lived in the UK, and like many other women my age, planned to get married and live happily ever after. Fortunately, while in my undergraduate program, I was taking Professor Dennis Vance's master's level course in membrane biology, which brought in distinguished scientists to give lectures. One lecturer was Jim Rothman, who had recently written a Scientific American article that I thought was just fantastic. I went to the seminar and asked lots of questions, and later Jim and I went for lunch. The next thing I knew, Jim had written to Dennis saying that I should apply to do a PhD with him. By then, I'd missed all the application dates, but Stanford said that I could bypass the early application process and just submit the formal application. I also had to scramble to take the GRE exam, which is required for admission. I then was invited to interview at Stanford. As part of the interview, I had to meet with every single faculty member – basically a set of very distinguished group Nobel laureates or soon-to-be Nobel laureates. It probably should have been intimidating but I was completely naïve! They all asked me why I had only applied to Stanford, but I just told them it was because it was the only school I wanted to go to. Anyway, I somehow got accepted! My parents said they'd mortgage the house and do whatever it would take to allow me to go. But then I learned that my tuition would be covered and that I'd have a stipend, so we'd be fine. I had absolutely not looked into what was needed to get into graduate school.

This was an opportunity that I just couldn't turn down, and my boyfriend agreed. Three years later, my then fiancé moved to Stanford to be with me, but it was just a total disaster, so we called it off! I had grown in confidence and found a new passion in research. But I worry this happens to a lot of women: you get derailed at that time in your life when your instincts say you should be nesting, and you don't have the confidence to think that you're good enough. It can really just be serendipity and having the right support around you that can push you forward. I was lucky that I had people like Dennis Vance, my undergraduate mentor Pieter Cullis and Jim Rothman who gave me that support and provided those opportunities. It was very fortuitous.

And how was it at Stanford – did you enjoy your time there?

Well, it also turned out to be serendipity that I joined the Biochemistry department at Stanford when it was at its prime. All of the faculty members were friends and they talked to each other about their science. Benches were randomly assigned within the department, so people mixed all the time. We had tea and cookies every day at four o'clock, as well as departmental retreats, faculty seminars and journal clubs. The department was full of energy and enthusiasm for science, with everybody knowing a little bit about what everybody else did. The faculty also taught classes for the incoming graduate students, and at the end of each class you had to write a research proposal; you basically had to identify a gap in the literature and write a research proposal for every class. By the time I graduated, I knew how to write grants and how to think about science. It was just such a wonderful learning experience.

Jim, of course, was very ambitious. He was a very driven scientist, and he expected the same from his students and postdocs. I guess we had our battles but, in the end, Jim taught me how to ask important questions, interpret my data, generate hypotheses and rigorously test them. I was also fortunate that I had a network around me and some fantastic people who became terrific peer mentors for me. And I think that's an important lesson for every student: you should become part of your department and institute and not just confine yourself to your lab. You need to talk to students and postdocs from other labs and to other faculty members. I was always disappointed when we had departmental retreats and I would see people having lunch with their own group – it's crazy. When you're troubleshooting, or stuck with your project, getting a completely different perspective on it can sometimes be the breakthrough you need.

Following your graduate studies, you moved to Ira Mellman's lab at Yale University for your postdoctoral research – what did you work on there?

While I was a PhD student, I thought about two people I might want to do a postdoc with. One was Jeff Schatz, who was doing beautiful work on mitochondria, and the other was Ari Helenius, who had pioneered the use of viruses to study cell biology. My husband Bill got a job at Yale, which was where Ari was based, so I applied to Ari's lab. But he turned me down! He always ran a small lab with just five or six people and he didn't have room, but he told me about Ira Mellman, who had just joined the Yale faculty. He said that he and Ira were collaborating on using viruses to study endocytosis, which is exactly what I wanted to do. So I wrote to Ira — I had no idea who Ira was — and asked him if I could join his lab. He said yes, and ultimately, I was co-mentored by both Ira and Ari – all my papers are from the ‘Mellenius lab’, as we called it.

I was a pure ‘bucket biochemist’ while I was at Stanford, so when I moved to Yale, I used it as an opportunity to learn experimental cell biology. I learned how to do subcellular fractionation and how to make monoclonal antibodies. I also did lots of in vivo labeling and pulse-chase experiments, aiming to biochemically dissect trafficking along the endocytic pathway.

How did you then decide what direction you wanted to go in, and where to go, when making the transition to setting up your own research group?

My time at Yale gave me a nice mixture of tools that I could take with me. At that point, my husband and I were a ‘two-body problem’ (note to employers, I like to think of these as ‘two-body opportunities!’). Bill had a faculty position at Yale, and I was also offered a position at Yale. But the position came with a heavy teaching load, and I was worried that, being a conscientious teacher, it would take me away from research. We also knew we wanted to have a family – in fact, our son was born while I was a postdoc – so we had this to consider, too. When we saw opportunities come up at The Scripps Research Institute, where there was no teaching or administrative duties, we both thought we should give it a go, as we could really focus on the research. We both moved to Scripps, and it turned out to be a great decision for us.

And what would be your advice to people who are at that point in their career, wanting to make the step into a faculty position?

Things have obviously changed and it's a lot more competitive now for sure. But I think you still need to have a vision of what you want to do – something you want to solve or figure out. Then you need to think about the immediate steps you need to take to accomplish that vision. You also have to ensure you're uniquely qualified, so that you've got something that gives you an edge and distinguishes you from your PhD mentor and your postdoc mentor.

It's also important to cast a wide net: apply to all sorts of places that could be a good fit and customize your application in each case. Remember that the environment you land in is going to influence what you do. Also remember that the place you go to first isn't necessarily the place you're going to end up in, so don't be afraid to take a job if it's not an exact fit. You might just find that it's a perfect place to start and you can then develop that longer-term vision of where you want to be.

You then moved on to serve as the Chair of the Department of Cell Biology at Scripps. How did this come about – was it part of your long-term plan? And what did you learn from this experience?

I'm not sure it was part of a plan, but I'd had lots of leadership roles throughout my life, starting in high school, so it wasn't a shock. In high school, I realized we had lots of really good people running for student council but only one person could win the election, so I rewrote our school's Constitution to allow more people to become members of the council. Even at university, I helped rewrite the curriculum so that I could get a bachelor's degree in cell biology. At each place, I've looked for opportunities to improve things. Maybe this all stems from the fact that, when my family went camping, my parents insisted that we always had to leave the campground cleaner than we found it! So, the last thing we did before we left the campground was to run all around and pick up all the litter. I now try to do that at each place I'm at: I try to improve things.

After 10 years of being at Scripps, Bernie Gilula – who was the chair that hired us – was promoted to VP of Operations, and the institute's President, Richard Lerner, asked me to take over as department chair. I was flattered but knew there were lots of professors in the department, my husband included, who were more senior than me. I went home to my husband and said, “Richard just asked me to be chair. What do you think?” And he just said, “Of course you – who else?” So, I was promoted from associate professor straight to chair. It was a great experience for me. As a department chair, you get to shape the environment and the culture of the place you work at. It gives you more influence, which is self-serving in some respects but also means that you can help other people.

After a successful stint at Scripps, you moved on to take on the position of Chair of the Department of Cell Biology at UT Southwestern Medical Center, where you had the chance to expand the department there. What spurred this move?

Well, I should point out that the other thing I did while I was at Scripps was to have a midlife crisis! My youngest child was heading off to college and I thought ‘What am I going to do with my time?’ So, I went back to school and got a master's degree in Executive Leadership. At the time, NIH funding was dropping, and we knew the system had to change – we couldn't just be doing boom-or-bust science and tripling the size of our departments. We needed to transform the enterprise of science. The master's degree taught me how to lead change, transform thinking and strategically make decisions. I really wanted to put the skills I learned to use, so I started looking for opportunities. UT Southwestern came up as an amazing organization – the cell biology department was moving into brand new space and expanding, and they wanted transformational leadership. The university itself was also willing to make changes. It was a great fit.

I also know that you give seminars to postdocs and junior faculty about the importance of good time management skills. Was this something that you have always been aware of or just something you became better at as your career progressed?

I learned time management skills in high school from doing a lot of activities. I played competitive sports, was in a community band, on Student Council, I edited a student newspaper and had lots of friends that I partied with. I realized that to do all these activities, in addition to my schoolwork, I needed to be able to organize my time. It was something that came very naturally to me. And, with time, I've also learned techniques to help me get even better, so I try to teach those skills and pass them on. In the late 90s, I read Stephen Covey's ‘The Seven Habits of Highly Effective People’ and it resonated with me (and I even got my kids to read it once they were older).

These time management skills are important when you're a faculty member and you've got lots of people demanding your time. But they're also important when you're a student or postdoc, for example when you're planning your experiments and thinking about how to organize your time, your thoughts, or your paper.

I know that you're also an advocate for women in science. In the 35 or so years since you've been a PI, we've seen some changes in the system but is there more that can and/or should be done?

Obviously, we need to carry on doing the basic things, such as making sure there's daycare available for people who need it. But we still are not at critical mass: we need to have more women – at least a third – on committees and boards to make sure we're hearing their voices. We just haven't reached that level yet. It's tough because we know the numbers drop: the women who are on committees end up doing too much and taking on more of a burden than their male colleagues. There are also gender differences, but we need to realize the value of those differences and how they can really improve the environment. And this extends beyond women to all aspects of diversity. The studies are very clear: diverse perspectives yield better science and better environments to work in.

As a woman, I feel that a part of being successful is believing in yourself. Sometimes you just have to push yourself just a little bit out of your comfort zone. Maybe sit at the front of the seminar room and ask questions – be visible. Don't be afraid to speak up. People will notice you and think about you when opportunities come up. If you can, try to find a sponsor – someone who is different from your mentor and who will give you those opportunities. Yes, the system needs to change but think about your sphere of influence and the things you can control; don't waste emotional energy on the things you can't control. As you move up the ladder, your sphere will increase, and you can have more of an influence.

We also talk a lot about having a balanced life, but we should remember it's just that – a balanced life but that might mean that it's not always a balanced week, or balanced months. If you decide to have kids, your life is probably not going to be balanced to begin with (while you're waking up in the middle of the night feeding babies and changing diapers)! But five or ten years down the line, all of a sudden, you'll look up and see that you've got amazing, independent kids who support you and bring happiness and joy to your life.

Yes, the system needs to change but think about your sphere of influence and the things you can control; don't waste emotional energy on the things you can't control. As you move up the ladder, your sphere will increase, and you can have more of an influence.

In 2020, you joined the Chan Zuckerberg Biohub in San Francisco – what's the main aim of the Biohub and what's your role in the organization?

The Biohub is part of the vision of Mark Zuckerberg and Priscilla Chan. Around the time of the birth of their first child, they decided that they wanted to commit their wealth to philanthropy. They launched the Chan Zuckerberg Initiative's science work in 2016 with the aspirational mission to help scientists cure, prevent or manage all disease by the end of the century. It sounds audacious, and some of my colleagues have scoffed at the idea. But I sometimes compare it to saying in 1900 that we want to send a man to the moon before the end of the century, which we managed to do.

If we really want to help scientists cure, prevent or manage all human disease, we need to understand human biology, we need new technologies to allow us to do this, and we need to change how we do science. That's what pulled at my heartstrings; we needed transformational change and a place that was collaborative, open and interdisciplinary. The Biohub model is setting the example for this. It was placed in the middle of three powerhouse universities that usually competed with each other, with the goal to bring them together and leverage their combined strengths in a collaborative manner to advance science. We fund investigators in those three universities who come to the Biohub every two weeks and share unpublished data. The number of inter-institutional collaborations, as measured by co-authored papers, increased an order of magnitude in the Biohub's first five years. In addition, the Biohub itself conducts its own intramural research, and has five technology platforms that help support and drive the science that's happening.

Are you enjoying this role? And how does it compare to being in a university or academic institute?

It's amazing. We completely changed how we do science. There are now two new Biohubs – one in Chicago and one in New York. The three hubs, together with a new Chan Zuckerberg Imaging Institute, are creating a synergistic and interactive research ecosystem. In academia, you might be in a department where one person is an HHMI investigator and gets lots of funding while the person in the lab next door is really struggling; this is because academia funds individuals who are all working on their own projects. But the Biohub model is supporting a scientific enterprise that works in unison to tackle big questions. I think it's an incredible vision. We're still building the plane as we fly it but, so far, it's going well and it's exciting to be part of it.

Chan Zuckerberg Science is also building communities. They pick areas like neuroscience or imaging, and they bring people together from diverse fields, at different career stages so that they can all share ideas, perspectives and technologies. Their philosophy of open science, collaboration and interdisciplinary research helps to advance science more quickly. It's also been amazing to see just how engaged Mark and Priscilla are – in addition to setting the overall strategy, they also go to the seminars and read the grants.

It all sounds fantastic. But do you think part of its success boils down to the fact that you're taking away the pressure to compete for funding?

I think that certainly helps, although my feeling is that competition is actually important to make sure people don't become complacent. But what we're really trying is to do things that couldn't be done in academia or in pharma, whether that's collecting large, high-quality data sets and disseminating them for other people to use, or developing new instruments, technologies and ways of analyzing data. We need to be able to link information across scales, from molecular to cellular to organismal. No one lab can do that and we're trying to bridge those gaps.

I think we also have to get away from the pressure to publish in the ‘most prestigious’ journals. This absolutely delays science, delays the communication of science, and delays careers; it's a very demotivating process – not to mention one that comes with very high financial costs. Publishing in those journals doesn't help us do better science.

If you could change one thing in academia, what would it be?

I think we have to value team science and think more about interdisciplinary collaborative research. I think we also have to get away from the pressure to publish in the ‘most prestigious’ journals. This absolutely delays science, delays the communication of science, and delays careers; it's a very demotivating process – not to mention one that comes with very high financial costs. Publishing in those journals doesn't help us do better science. So why do we keep worshiping at that altar?

The people with the gold make the rules. So, if the Wellcome Trust, HHMI, the NIH, the MRC, the DFG – all funders – exerted their influence more strongly on these issues, we could move the system forward. Considering most work published in so-called top journals was conducted with government funding, there needs to be far better alignment between these journals' for-profit model and the needs of scientists and the public.

I see people who are good scientists and have been consistently productive with beautiful JCS, JCB or MBoC papers. They publish one, two or sometimes three papers a year, all of which move the field forward and add to the scientific knowledge base. In my mind, that's good science that deserves to get funded.

The Chan Zuckerberg Initiative is also making significant contributions toward rapid and open dissemination of scientific results, with its support of the bioRxiv and medRxiv preprint platforms. Open science and preprint publishing are core values of both Chan Zuckerberg Initiative and the Biohub Network.

Finally, is there anything our readers would be surprised to find out about you?

I think some people might be surprised to find out that I spend a lot of my Sundays on the couch watching football. Go 49ers!

Sandra Schmid's contact details: Chan Zuckerberg Biohub – San Francisco, 499 Illinois Ave, San Francisco, CA 94158, USA.

E-mail: sandra.schmid@czbiohub.org

Sandra Schmid was interviewed by Seema Grewal, Executive Editor for Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.