Halil Aydin

Human cells are enclosed by a plasma membrane. Inside the plasma membrane, there are many other membranes which define the external boundary and the spatial identity of intracellular compartments, or organelles. Many organelles have very distinct shape and subcellular localizations but they are also dynamic and they interact with each other. The proper morphology and spatial distribution of organelles are important for many key cellular processes including signaling, polarization, and development. The goal of the Aydin lab is to understand how organelles adapt their morphology and spatial distribution to changing cellular conditions and how proteins and protein complexes that are associated with membranes regulate the structure and function of the organelles in cells.

Mitochondria are essential eukaryotic organelles that are involved in numerous key cellular functions, including energy production, metabolism, signaling, and regulated cell death. Our research interests are largely directed towards elucidating the molecular mechanism of regulated mitochondrial morphology for developing a molecular understanding of mitochondrial function in human cells. We are particularly interested in learning how mitochondrial protein networks communicate cellular signals to regulate mitochondrial morphology and function, and how perturbations of this interplay underlie the development and progression of the disease. We primarily utilize structural methods such as electron cryo-microscopy (cryo-EM), biochemistry, biophysics, and cell biology tools to study the molecular mechanisms that regulate mitochondrial dynamics. Characterizing the mechanisms that govern mitochondrial morphology and function will enable us to therapeutically manipulate mitochondria in the future. We aim 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.

For a full list, please see: https://www.ncbi.nlm.nih.gov/myncbi/1xgEwwaTqUVQR/bibliography/public/

1. *Bennett, J. A., *Steward, L. R., Rudolph, J., Voss, A. P., Aydin, H. (2022) The structure of the human LACTB filament reveals the mechanisms of assembly and membrane binding. doi: 10.1101/2022.04.21.489104. PLOS Biology (In press)
*These authors contributed equally.

2. *Manicki, M., *Aydin, H., Abriata, L. A., Overmyer, K. A., Guerra, R. M., Coon, J. J., Dal Peraro, M., Frost, A., Pagliarini, D. J. (2021) Structure and functionality of a multimeric human COQ7:COQ9 complex. Molecular Cell (82) 1-17. doi: 10.1016/j.molcel.2022.10.003
*These authors contributed equally. 

3. 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 Jun 15;534(7608): 562-565. doi: 10.1038/nature18595.

4. Aydin, H.*, Taylor, M. W.*, and J. E. Lee. Structure-guided analysis of the human APOBEC3-HIV restrictome. Structure 2014 May 06;22(5):668-684. doi: 10.1016/j.str.2014.02.011.
*These authors contributed equally. 

5. Aydin, H., Al-Khooly, D., and J. E. Lee. Influence of hydrophobic and electrostatic residues on sars-coronavirus S2 protein stability: Insights into mechanisms of general viral fusion and inhibitor design. Protein Science 2014 May;23(5):603-617. doi: 10.1002/pro.2442. 

6. Aydin, H., Cook, J.D., and J.E. Lee. Crystal structures of beta- and gammaretrovirus fusion proteins reveal a role for electrostatic stapling in viral entry. Journal of Virology 2014 Jan;88(1):143-53. doi: 10.1128/JVI.02023-13. 

7. Aydin, H., Smrke, B.M., and J.E. Lee. Structural characterization of a fusion glycoprotein from a retrovirus that undergoes a hybrid 2-step entry mechanism. The FASEB Journal 2013 Dec;27(12):5059-71. doi: 10.1096/fj.13-232371.

8. Aydin, H.*, Azimi, F. C.*, Cook, J. D.*, and J. E. Lee. A Convenient and General Expression Platform for the Production of Secreted Proteins from Human Cells. The Journal of Visualized Experiments 2012 Jul 31;(65). pii: 4041. doi: 10.3791/4041.
*These authors contributed equally.