Research Projects

Tight regulation of metabolic homeostasis and molecular composition is maintained by compartmentalization in neurons (Virga et al., 2024; Sung, 2025). Due to this, both the endoplasmic reticulum (ER) and mitochondria serve functions that extend beyond their classical roles in protein synthesis, trafficking, calcium regulation, and ATP production. Physical contacts between the ER and mitochondria have been recognized as key sites for ion and lipid exchange, intracellular signalling, and membrane dynamics (Csordás et al., 2018). Ongoing research continues to uncover additional functions associated with this inter-organelle contact sites. Despite the importance, contribution of ER- mitochondria contacts in neuronal compartment-specific functions modulating synaptic plasticity remains obscure. Synaptic plasticity is a critical neural process involved in the formation and storage of memory (Hebb, 2005). In the course to learn about the various mechanisms modulating synaptic plasticity, the detailed functional contribution of ER-mitochondria contact sites needs to be elicited. Accumulating evidence implicates dysregulation of plasticity-related mechanisms in the etiology of various neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and Alzheimer’s disease (Citri and Malenka., 2008). Therefore, elucidating the molecular and cellular underpinnings of synaptic plasticity is essential to understand both normal brain function and the mechanisms driving neuropathology. This project aims to develop and apply genetically encoded FRET sensors to visualize nanoscale ER–mitochondria contacts in neurons. Using targeted fluorophore-tagged proteins, we will create a FLIM-FRET-compatible sensor. Functional and structural plasticity will be assessed in hippocampal slice cultures using two-photon glutamate uncaging and electrophysiology. Finally, the sensor will be used to study ER–mitochondria interactions during synaptic plasticity in an Autism mouse model to explore their role in neurodevelopmental disorders. References: • Virga DM, Hamilton S, Osei B, Morgan A, Kneis P, Zamponi E, Park NJ, Hewitt VL, Zhang D, Gonzalez KC, Russell FM. Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo. Nature Communications. 2024 Mar 8;15(1):2142. • Sung H. Compartmentalized regulation of organelle integrity in neurodegenerative diseases: lessons from the Drosophila motor neuron. Neural Regeneration Research. 2025 Jan 1;20(1):195-6. • Csordás G, Weaver D, Hajnóczky G. Endoplasmic reticulum–mitochondrial contactology: structure and signaling functions. Trends in cell biology. 2018 Jul 1;28(7):523-40. • Hebb DO. The organization of behavior: A neuropsychological theory. Psychology press; 2005 Apr 11. • Citri A, Malenka RC. Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology. 2008 Jan;33(1):18-41.