Jonathan Sweedler (BSD/CABBI/MMG), Professor in Chemistry and the Neuroscience Program and a research member with the Cancer Center at Illinois’ JumpStart Program, was recently awarded a $1.5 million NIH grant for the installation of a high-end mass spectrometer which will allow Jonathan’s lab to provide Illinois faculty and other NIH researchers with more sensitive and informative single-cell and tissue imaging experiments. Interview with Prof. Sweedler follows.

Can you tell us a bit about your background, Jonathan?
It’s hard for me to say this, but I’ve now spent 32 years here at Illinois. I’m a chemist who works in neuroscience, endocrinology, and other areas using mass spectrometry approaches to measure the molecules within and around cells and small tissues, and to see how they change as a function of health, behavior, and disease. The thing that makes our group a little unusual is that the chemical characterization techniques and protocols we use are created by our group. In other words, the analytical chemistry and bioengineering aspect of group research is that we create new techniques, and more specifically, we’ve really pushed new approaches for single-cell chemical measurements.

Why are single-cell measurements important?
Whether it’s the brain where differences between cells drive brain function or in development biology where different cells create new organs, the differences between cells determine their function. In the case of cancer, you might want to know about the initial cells showing signs of cancer before they proliferate and to determine how these initial cancer cells impact the cells around them.

What ignited your work in cancer research?
I’ve always tried to avoid research areas that have many other researchers. And cancer research sort of scared me because it seemed like there’s an ‘infinite number’ of people studying cancer. So, I have looked at cancer research and thought of it as beyond my ability to compete.

However, I have realized that other groups do not make the single cell chemical measurements that we do, and so we have started considering cancer research. When approached about looking at a tumor model to examine cell heterogeneity, I realized we can make measurements of the differences between the cells within a tumor; we do see striking differences between the cells.

We have a tool in our group that emphasizes the chemical state of the cells. That is important information for cancer research, as we should be able to follow how a new drug impacts the individual cells in a tissue and what the drug is actually doing to the cell.

A cell has a genome and a transcriptome; the cell transcripts encode its proteins. The measurement of single-celled transcripts is a fairly well-developed field, and single-cell proteomics has made great strides. It’s the metabolome – the small molecules themselves – that tell you the state of the cell. The metabolome is being recognized as the most dynamic part of the cell, and it’s the class of molecules we have the least ability to measure. Just recently, in fact, Nature named single-cell metabolomics as one of the seven technologies to watch in 2023, and they highlighted the unique work we are doing. So, our technique is fitting in very well with trying to understand how cells go bad during cancer.

How then did you get involved specifically with the Cancer Center at Illinois and the JumpStart Program?
Well, with our recent progress in the single-cell area, Rohit (Bhargava) and others said to me, “You know, you should really be applying this to cancer biology.” The JumpStart Program funds are partially supporting two graduate students to try initial experiments on applying our mass spectrometry-based approaches to cancer related projects. Thus, the JumpStart program is leading to new collaborations and new proposals. The JumpStart Program has allowed me to take a small part of our group and ‘test the waters’ of cancer research. This has worked really well.

What would you say to other scientists at Illinois who are not presently involved in cancer research?
If your expertise is biological technology, bioengineering, chemistry, or many other relevant areas, consider if you can have an impact on cancer research; through the CCIL, there may be funding to test your ideas. Perhaps more importantly, there’s expertise and a growing group of people here who are willing to work with you. It’s definitely something to consider.

What has brought you joy in your storied career here at Illinois?
I came here from California and thought this was a great place to start my career. I expected to spend five or six years here and move back to the West Coast. And here I am 30 years later. And one of the things that Illinois offered is a wonderful collaborative work environment and the opportunity to work outside of my primary discipline. I’ve done that for most of my career. It’s been a really wonderful time to learn what others are doing and interact between labs.

In my work, my group has created analytical chemistry approaches that don’t really care what cell they are characterizing. So, whether it’s a human cancer cell, or a neuron from a rat, a sea slug, or another creature, we can measure it. This has led to some interesting collaboration. For example, Gene Robinson convinced us almost twenty years ago to explore peptides in the honeybee, and we learned how neuropeptides change as a function of bee behavior. We have since explored samples from cows, pigs, songbirds, crabs, sea urchins, comb jellies, and many more. Many of these one-off projects have been non-funded – because how do you get funding for something like that! – but the articles are unusual and high-impact. These collaborative studies highlight what Illinois has to offer. This partnership with Rohit (Bhargava) and the Cancer Center at Illinois is another great example of this at Illinois.

Jonathan is the James R. Eiszner Family Endowed Chair in Chemistry, is affiliated with the Neuroscience Program, the Cancer Center at Illinois, the Beckman Institute for Advanced Science and Technology, Department of Molecular and Integrative Physiology, Department of Bioengineering, and the Carle Illinois College of Medicine. Jonathan is also the Editor-in-Chief of the journal Analytical Chemistry.