Antonina Roll-Mecak, Ph.D.

Our every movement and thought is brought about by a complex network of neuronal connections precisely patterned through the dynamic organization of the microtubule cytoskeleton, a network of protein polymers composed of αβ-tubulin building blocks. The neuronal processes that crisscross our brain to enable information retrieval and integration rely on dense microtubule bundles, both to stabilize their structure, and to serve as tracks for the bidirectional cellular traffic that is essential for the efficient communication between distant neuronal compartments. The microtubule cytoskeleton is so central to cell function that its disruption underlies neurodegeneration, neurodevelopmental disorders, cancers, and pathogens often hijack it. Even subtle perturbations in microtubule organization and dynamics are sufficient to cause cognitive and behavioral deficits. Microtubules were assumed to be inert transport tracks, but by developing new methods my group revealed that they encode information – a "tubulin code" that regulates a broad array of effectors – and thus serve as micron-scale signaling platforms. Building on this discovery, my research program seeks to answer the following fundamental questions: how information is chemically, genetically and conformationally encoded in microtubules to direct traffic and cytoskeletal network remodeling, how this code responds to extracellular signals, stress and injury, how it contributes to neuronal fitness, and how it breaks down in disease. To answer these questions my team integrates analyses at high spatial and temporal resolution using diverse structural biology approaches (X-ray crystallography, cryo-EM, in situ cryo-ET) and light imaging modalities (single molecule imaging, label-free imaging, expansion microscopy), with biochemistry, biophysics, proteomics, chemical biology and integrative modeling, with the ultimate goal of achieving a multiscale understanding of cytoarchitecture development and adaptation, shed light on disease etiology and identify therapeutic avenues of intervention.

Dr. Antonina Roll-Mecak is Senior Investigator and Chief of the Unit of Cell Biology and Biophysics at the National Institutes of Health, with appointments in NINDS and the Biophysics and Biochemistry Center at NHLBI. She earned her B.E. in Chemical Engineering from The Cooper Union and her Ph.D. in Molecular Biophysics from Rockefeller University, where she studied protein translation mechanisms. As a Damon Runyon postdoctoral fellow with Ron Vale at UCSF, she identified spastin, a microtubule-severing enzyme linked to hereditary spastic paraplegia and characterized its mechanism of action. She joined the NIH in 2010 to lead the Unit of Cell Biology and Biophysics. Early recognition of her work included a Burroughs Wellcome Career Award, a Searle Scholar Award, and the Biophysical Society's Margaret Dayhoff Award in 2015. In 2017 she was named a Keith R. Porter Fellow of the American Society for Cell Biology. In 2022, she received a NIH Director's Challenge Innovation grant to generate a 4D map of the tubulin code in human neurons and in 2023 was recognized with the Biochemical Society's International Prize. In 2023 she received the NINDS award for mentoring junior faculty and in 2025 was honored with the Protein Society's Hans Neurath Award for her work on the tubulin code and contributions to protein science.