Matt Lycas, Ph.D.

I first walked into a research lab in 2009 as a high school student, helping troubleshoot an electron microscopy data pipeline at the NIH. I didn't fully understand what I was looking at yet, but something about seeing biology at that resolution stuck with me. The following year I got my first taste of fluorescence microscopy working on Drosophila brains, and that was it — I was hooked. The idea that we could map the brain in such detail and develop real understanding for how it worked felt unbelievably exciting — I wanted to see just how much we could learn.

I spent my undergraduate years at the University of Virginia pursuing that question from the behavioral side, studying how the brain encodes motivation and addiction through narcotics research in animal models. From there I returned to the NIH as a postbac, where electrophysiology gave me a more direct window into neurotransmitter release and the functional logic of neural circuits. I moved to Copenhagen wanting to bring everything together — to study dopamine, the molecule sitting at the intersection of much of this motivation research, with the sharpest tools available.

In Copenhagen I dove headfirst into single molecule localization microscopy, and it changed how I thought about biological space. Using dSTORM to map the nanoscale organization of the dopamine transporter felt like finally seeing the machinery behind the behavior. I began exploring expansion microscopy to validate and extend those findings, and found myself increasingly drawn to the sample preparation side — what were we actually preserving when we fixed tissue, and what were we losing? Cryo-electron tomography sharpened that question considerably. Seeing the consequences of chemical fixation at the synapse up close made me want to do better.

That drive carried me into my postdoctoral work, where I focused on pushing expansion microscopy toward true ultrastructural preservation. Working with cryo-fixation and moving away from aldehyde-based workflows dramatically improved sample antigenicity, and that opened an unexpected door: if the preservation was good enough, you could start making quantitative estimates of protein complex abundance directly from the expanded sample. That became qExM — a method for in situ quantification of endogenous targets with nanoscale spatial information. In parallel, live super-resolution imaging of mitochondrial cristae dynamics became a powerful tool for understanding the dynamics of mitochondria.

I have since joined Janelia Research Campus, where I am developing expansion microscopy further in the pursuit of connectomics research.