Maxim Prigozhin, Assistant Professor in MCB and Applied Physics, has been awarded the 2026 Maximizing Innovation in Neuroscience Discovery (MIND) Prize for a bold proposal to transform how scientists visualize the brain at the nanoscale. The competitive award supports high-risk, high-impact ideas in neuroscience, with a particular focus this year on neurodegenerative disease.
Prigozhin’s lab sits at the intersection of physics and biology, developing advanced imaging tools that allow researchers to see the brain with unprecedented detail. While his work has long centered on fundamental questions in brain structure and connectivity, the MIND Prize project pushes his technology directly into the realm of disease.
“It actually took me—it was an opportunity for me to learn more about what the challenges are in that field, and how my technique could be applicable to those challenges,” Prigozhin said. “And I believe it truly could have a substantial impact.”
Bridging a Fundamental Gap in Brain Imaging
Prigozhin’s lab focuses on developing tools that allow scientists to visualize the brain at nanometer resolution. Traditionally, neuroscientists have relied on two distinct imaging approaches.
Electron microscopy (EM) can reveal exquisite ultrastructural detail—membranes, synapses, organelles—but it cannot distinguish between different molecular identities. “You see the cells, the membranes, the synapses,” Prigozhin explains. “But you don’t know what is the functional identity of that neuron.”
Fluorescence microscopy, by contrast, can label specific proteins—dopamine-producing neurons, inhibitory cells, pathological aggregates—but is fundamentally limited in resolution by the physics of light.
The field has long attempted to overlay the two methods, capturing fluorescence images first and then aligning them with electron micrographs. But as Prigozhin noted, this approach is technically demanding and often imprecise. “It’s very difficult to align the two data sets to figure out which fluorescence signal corresponds to what,” he said.
His proposal aims to eliminate that trade-off entirely.
A New Imaging Strategy
The project – “Cathodoluminescence Electron Microscopy for Nanoscale Molecular and Ultrastructural Imaging of Brain Pathology” – builds on more than a decade of work in Prigozhin’s postdoc and then his own lab to develop an unconventional imaging approach based on cathodoluminescence (CL), a phenomenon in which light is emitted when a material is excited by an electron beam.
Because electrons have much shorter wavelengths than photons, excitation can be confined to just a few nanometers. By engineering specialized luminescent probes—“cathodophores”—that emit light under electron beam stimulation, Prigozhin aims to detect specific proteins directly within an electron microscope.
“It’s really a type of imaging that straddles these two worlds,” he said. “It has similarities to fluorescence and electron microscopy, but it’s not exactly either one.”
The key innovation is that both ultrastructural information and molecular signals would be captured simultaneously using the same electron beam. That would eliminate the need to painstakingly align separate fluorescence and EM datasets and could enable true multicolor molecular imaging at nanoscale resolution.
Over the past six years, Prigozhin and his team have built a dedicated CL microscope, developed probe chemistry, and generated unpublished data demonstrating multicolor imaging in biological samples. “Ultimately, we think we kind of figured it out,” he said. “We think we can really do it.”
Applying the Technology to Alzheimer’s Disease
The MIND Prize project will apply this imaging platform to brain tissue from a mouse model of Alzheimer’s disease. The team plans to label multiple neuronal proteins—including amyloid-beta (Aβ) and phosphorylated tau (pTau)—while simultaneously reconstructing synapses and cellular ultrastructure in three dimensions.
The goal is to generate the first 3D multicolor electron microscopy map of diseased brain tissue at nanoscale resolution.
Such an integrated dataset could reveal how pathological protein aggregates are distributed within specific cell types and synaptic compartments—information that is difficult or impossible to obtain using current methods.
“Any technique is only as useful as the results and insights that it produces,” Prigozhin said. “So it is important to think about how to get to that next step of biological discovery.”
Although the technology emerged from a highly biophysical research program, Prigozhin believes its greatest value lies in enabling new biological questions. “You really need that physics background to understand what’s going on with imaging,” he said. “But ultimately, you have to convince people that your physics is going to be useful for their problems.”
Our team is developing a revolutionary microscopy technique that solves this problem by creating special molecular “tags” that glow when hit by an electron beam, allowing us to simultaneously capture incredibly detailed images of brain structures while pinpointing the exact locations of disease-causing proteins. Using this new method, we will study brain tissue from mice with Alzheimer’s-like disease, creating the first-ever 3D color map showing where toxic proteins build up within the brain—like having Google Street View for the brain. This technology could transform how researchers study brain diseases, potentially accelerating the development of new treatments by revealing exactly what goes wrong inside diseased brains at a level of detail never before possible.
A Collaborative Effort
In preparing to translate his imaging platform into the neurodegeneration space, Prigozhin sought input from colleagues across the department, where roughly half the faculty focus on neuroscience.
“I wanted to talk to people on the neuroscience side to help me frame my project correctly,” he said. Faculty members Catherine Dulac, Florian Engert, Naoshige Uchida, Venkatesh Murthy, and Sean Eddy offered feedback on how best to connect the imaging approach to pressing questions in brain research.
“Pretty much everyone whom I asked agreed to spend time with me,” Prigozhin said. “It really improved my presentation and also helped me understand what the challenges are in neuroscience research.”
Dulac adds, “I was thrilled to learn from Max about his new ideas and exciting progress towards developing such a revolutionary microscope. This new tool will clearly transform the field of neuroscience, and I want to be among the first in line to use it!”
Eddy comments, “Max’s work is a great example of the kind of cross-disciplinary work that attracted me to the Harvard science community in the first place – a creative and unexpected combination of applied physics and structural biology, leading to a terrific new technology. I’ve really enjoyed watching Max and his lab doing all the hard work necessary to bring this idea to fruition.”
Prigozhin emphasized that this support was particularly meaningful as a junior faculty member. “It’s very important to have support,” he said. “When you see that people are willing to spend time with you and are encouraging, that really builds confidence.”
Expanding the Toolkit for Neuroscience
Although cathodoluminescence has so far been underutilized in biological imaging, Prigozhin believes it could become a broadly accessible tool. In principle, existing electron microscopes in shared facilities could be upgraded with CL capabilities, enabling nanoscale molecular imaging across many laboratories.
The long-term vision extends beyond Alzheimer’s disease. By allowing scientists to simultaneously map molecular markers and ultrastructure, the approach could transform studies of healthy brain circuits as well as a range of neurodegenerative conditions.
Ultimately, the MIND Prize will allow Prigozhin’s lab to move from proof-of-concept demonstrations to large-scale, disease-focused applications—testing whether a fundamentally new contrast mechanism can open a clearer window into the molecular and structural architecture of the brain.
