Q: What initially drew you to the APS?
Kira: I first learned about the APS through my mentor, whose research used synchrotron X-rays to study neurons. His group had observed structures containing high concentrations of iron, and because neurons share some characteristics with pancreatic beta cells, we wondered whether we might find something similar in the cells I study.
Pancreatic beta cells are the only cells in the body that produce and secrete insulin, which helps regulate blood glucose. My research examines how proteins and metals such as zinc, iron, and calcium interact in these cells, including how those relationships change during obesity-associated inflammation and potentially contribute to diabetes.
Using the APS gave us a new way to investigate those questions by showing where different elements are distributed within individual beta cells and allowing us to quantify them.
Q: Can you describe the research you’ve conducted at the APS?
Kira: My APS research uses hard X-ray fluorescence microscopy at the 2-ID-D beamline to examine the elemental composition of pancreatic beta cells. We know, for example, that these cells contain substantial amounts of zinc because of its role in insulin production and secretion, but understanding exactly where metals are located within cells can be challenging.
Some conventional fluorescent probes can respond to more than one metal, making it difficult to determine whether a signal comes from zinc, calcium, or another element. Synchrotron X-ray fluorescence allows us to identify elements unambiguously and quantify extremely small amounts within individual cellular compartments.
In our first studies, we mapped the subcellular distribution of multiple elements in pancreatic beta cells. That work gave us a more complete picture of their metallome, including intriguing iron-rich structures that have become an important focus of my research.
Q: What role did the APS play in enabling or advancing your work?
Kira: One of the most important discoveries enabled by the APS was those iron-rich structures, which we call iron puncta because they appear as small, punctate features throughout the cell. Other techniques I had used primarily detected free iron, representing only a small portion of the iron present in a cell.
X-ray fluorescence allowed us to see total cellular iron and revealed structures we hadn't observed before. We have since found evidence that these structures are dynamic. When cells are exposed to more iron, the puncta accumulate it, suggesting they may have a role in how the cell handles or stores iron.
We don't yet know exactly what these structures are or what biological function they perform. Being able to see them has opened a new set of questions about iron biology in pancreatic beta cells.
Q: Has anything unexpected come out of your work with the APS, either in your results or in the process itself?
Kira: One of the most rewarding surprises has been the collaboration itself. I’m a molecular and cell biologist, so I bring very different expertise from the scientists who develop and operate X-ray techniques at the APS. Working together allows us to ask questions neither field could necessarily address alone.
That collaboration is now helping us develop correlative microscopy that combines synchrotron X-ray fluorescence with confocal microscopy. X-ray fluorescence tells us where elements are located, while confocal microscopy allows us to identify cellular compartments.
When we overlay measurements from the same cell, we can begin to ask not only where metals are but also which cellular structures they are associated with. For me, that exchange of expertise has been one of the most exciting parts of working at the APS.
Q: What impact has your research at the APS had on your work so far? What are you excited about exploring next?
Kira: Using the APS has changed the trajectory of my research. I was already interested in metals and their roles in cells, but being able to map and quantify multiple elements has revealed questions I expect will shape my work for years.
I’m particularly excited about advancing correlative microscopy. Combining elemental maps with detailed images of cellular structures could help us determine the identity of the iron puncta and understand how they change under different experimental conditions. It may also help us explore interactions between iron, zinc, and other elements in greater detail.
More broadly, these measurements can reveal aspects of pancreatic beta-cell biology that were previously difficult to see. Each new element or structure we identify creates another opportunity to understand how these cells function in healthy and disease states.
