Outside the Lab Professional development, Analytical science

The Analytical Neuroscientist

Sitting Down With… Jonathan Sweedler, James R. Eiszner Family Endowed Chair in Chemistry, Director of the School of Chemical Sciences & Professor of Neuroscience and Molecular & Integrative Physiology at the Beckmann Institute, University of Illinois, USA

02/25/2022 | Interview

I was always into science – be it using a ham radio or making model rockets. In fact, in California, when I grew up, they had a ban on model rockets, so I was busy writing to state legislators to try and change the law – at about 12 years old. Soon after I became honorary first president of the local rocket club (which was mostly adults). I had around seven years’ worth of science courses in high school having changed my schedule around to accommodate the extra classes. I was always going to study science in college, and I guess I liked exothermic reactions, so chemistry was the one I went for. Though I did also study classical Greek as a minor…

The hard part was figuring out what I actually wanted to do as a career. I was interested in applying chemistry to biology and the brain, but I ended up getting a fellowship to work at the Lawrence Livermore National Lab as an undergraduate. Livermore is one of the two main weapons labs in the US – though I was working on analytical projects, which is what made me decide to stay in analytical chemistry. But I remained interested in neuroscience and, once I finished my analytical chemistry PhD, that’s what I decided to focus on during my postdoc at Stanford.

Yes. He was my first mentor and, really, the reason I am an analytical chemist. He was the only person I’ve ever met who genuinely had a photographic memory. You could ask him a question and he’d tell you to look up a paper – he’d know the journal, year of publication, the page number and even where on the page the relevant paragraph was. It was remarkable. And yet he’d sometimes forget to meet you after lunch! More importantly, he was a truly creative thinker with a broad knowledge base who always had a unique perspective on any given problem – and he’d encourage his students to explore new and crazy ideas. (It helped that the budget at Livermore was limitless, as far as I was concerned; I was working with FTIR and MS instruments back in the early 1980s, which just wasn’t possible anywhere else.) Creative problem solving is something I’ve valued throughout my career – and often just asking myself “What would Tomas have done?” does the trick!

In planning my postdoc, I was trying to figure out how I could study the brain from the point of view of a chemist – a daunting prospect. One way would be to simplify the problem by working on a simpler organism. So I started looking into researchers working on things like sea slugs, which have around 10,000 neurons, a number I can comprehend. I also needed to find a chemist to support this idea, something I was able to do at Stanford with Richard Zare and Richard Scheller. At UIUC, I continued this research area. I was discussing these research ideas with a physiology professor who suggested I go to Friday Harbor Marine Lab, San Juan Island, Washington, to learn about some of these organisms. I even ended up doing a sabbatical at Hopkins Marine Station in California learning fundamental neuroscience of marine organisms. I got paid to learn, be on the beach, and to scuba dive – it was great! A lot of people said I was crazy trying to learn new skills at the stage in my career when you’re supposed to be your most productive, but it was invaluable. I’ve used the practical skills I learned throughout my career and it also redefined me as a researcher.

When people start out in academia, in any field, they often want to answer the big questions – for example, how can we cure cancer? But if you’re going to get anywhere with questions like that, you need to ask first yourself, “Why me?” Or put another way, “What new skills, background, or perspectives can I bring to the problem?” And that’s where taking a slightly unusual path might be beneficial. It’s also important to carefully choose which area to specialize in. I never want to be doing the same thing as someone else, where you’re worried about getting scooped. The trick is to find something that really matters but that nobody else is doing.

Yes, you could say that. I’m in my 30th year at the University of Illinois and my group is half analytical chemistry and half physiology / neuroscience– with many sub-niches. People have left my group and become professors of neuroscience, and I don’t have a degree in neuroscience, which is pretty unusual. And it is funny to think about the fact that I’m training the next generation of teachers in a field I have no (formal) credentials in! But working across traditional disciplines and boundaries is something I enjoy – and I think it does foster original thinking.

I’m proud of having topped the Analytical Scientist Power List a couple of times now, but I’m delighted that two of my former students –Lingjun Liand Amanda Hummon – have also made this year’s list. Nothing makes me more proud than seeing my former students, from across the world, succeed in their careers.

I’ve always found it hard to accept accolades. I used to belittle them – saying it was a fluke or that they don’t mean anything. There are so many talented people out there, so why me? But I also don’t want to downplay my own research, which I think is important (otherwise I wouldn’t be doing it). So now my reaction is: “Wow, that’s great – and thank you!” But it’s also fun. Our local newspaper normally runs a story about it, it’s on the front page of my university – even my neighbors say congratulations! The Power List does seem to resonate with people. But fundamentally, I’m still surprised.

Yes, I’d say they are. But I still think there are some biases people sometimes aren’t aware of. For example, when we ask people to recommend someone for a new associate editor position, their first instinct is often to pick someone local to them – geographically, racially or in terms of specialization. But when you ask them to think of people from outside their comfort zone, you’ll often get a different name at the top of their list. We need to continue to push people to broaden their outlook. With these efforts, you’ll see both an increase in diversity and quality. And that’s key for The Power List – encouraging a more diverse list of nominees.

When I was hired at the University of Illinois 30 years ago, my research proposal outlined projects to determine the content of individual neurons – and creating single-cell measurements has been a major focus of my work ever since. During this time, single cell transcriptomics has flourished and has surpassed other omics-based single cell measurements. The situation is now shifting back to chemical measurements, and the last decade, in particular, has seen amazing progress in the field of single-cell chemical characterization – enabling measurements of the metabolites, peptides, and more recently, proteins within cells. We now have methods currently available that can provide in-depth molecular coverage of a specific cell, whereas others provide less coverage but can assay hundreds to thousands of individual cells. The field is being driven by a number of very creative scientists and it is fun to see the clever approaches different groups are taking.

I wonder if any of my students have asked themselves, “What would Jonathan do?” – just as I have done in the past with Thomas Hirschfeld – that would be quite the legacy. I keep in contact with almost all of my former graduate students and postdocs. Every once in a while, we have reunions. There are over 100 now and that’s an incredible number of lives to have touched. And it’s great when someone comes up to me and says, “You don’t know me but I work for your former student, so you’re my academic grandfather” – great grandfather in some cases. Which is a little strange... Fortunately, academic generations are relatively short!