Halil Aydin

Education

Ph.D.: University of Toronto, 2016
Postdoctoral Fellow: University of California, San Francisco 2016-2020

Areas of Expertise

Neurobiology and Neurodegenerative Disease, Structural Cell Biology, Electron Cryo-Microscopy (cryo-EM), Membrane Biology, Molecular Biophysics, Proteins and Enzymology.

Awards and Honors

• Boettcher Webb-Waring Biomedical Research Award
• Human Frontiers Science Program Postdoctoral Fellow
• Ontario Graduate Scholar
• Stuart Alan Hoffman Prize
• University of Toronto Fellow

Research Statement

How do neurons control the shape and spatial distribution of organelles in support of their function? Neurons are morphologically complex, polarized, and high-energy demanding cells that are responsible for essential nervous system functions. This structural complexity is critically important as it underlies nearly every aspect of neuronal function, and its loss is associated with numerous neurodegenerative and psychiatric disorders. Mitochondria are essential organelles in regulating neuronal physiology and cellular functions more broadly. My research focuses on characterizing conserved pathways that regulate the morphological and functional plasticity of mitochondria in neurons and reveals how this enables the nervous system to function. Our laboratory utilizes a multi-disciplinary approach that integrates structure determination by electron cryo-microscopy (cryoEM) with biochemistry, biophysics, and cell biology techniques to bridge detailed structural studies with a deeper knowledge of mitochondrial function to advance our understanding of how cellular machines function normally, and how they are corrupted by disease. These approaches enable us to perform robust quantitative analysis of membrane-associated mechanisms and thus bridge length scales from organelles and their internal structures like sheets and cristae (microns) to tubules and leaflets (nanometers), and finally to nearest-neighbor atomic interactions (Angstroms). The long-term goal of my research laboratory is to develop innovative approaches to understand how biomolecular machines function at biochemical depth and decipher the link between organelle regulation and its relationship to human disease. Overall, we provide quantitative explanations of membrane-associated mechanisms in cellular organelles and test our understanding of how they function within intricate cellular pathways.

Selected Publications

• von der Malsburg, A., Sapp, G. M., Zuccaro, K. E., von Appen, A., Moss III, F. R., Kalia, R., Bennett, J. A., Abriata, L.A., Dal Peraro, M., van der Laan, M., Frost, A.+, Aydin, H.+ Structural mechanism of mitochondrial membrane remodeling by human OPA1. Nature 2023 620:1101-1108 https://www.nature.com/articles/s41586-023-06441-6 +Co-corresponding authors.
• *Bennett, J. A., *Steward, L. R., Rudolph, J., Voss, A. P., and Aydin H. The structure of the human LACTB filament reveals the mechanisms of assembly and membrane binding. PLOS Biology 2022 20(12): e3001899 https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.30... * These authors contributed equally. 
• *Manicki, M., *Aydin, H., Abriata, L. A., Overmyer, K. A., Guerra, R. M., Coon, J. J., Dal Peraro, M., Frost, A., Pagliarini, D. J. Structure and functionality of a multimeric human COQ7:COQ9 complex. Molecular Cell 2022 82, 1-17 https://www.sciencedirect.com/science/article/pii/S1097276522009601 * These authors contributed equally. 
• Aydin, H., Sultana, A., Li, S., Thavalingam, A., and J. E. Lee. Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex. Nature 2016 534:562-565. https://www.nature.com/articles/nature18595