MIRO interaction mapping for neuronal mitochondrial dynamics

Objective

MiroMap is a highly interdisciplinary project designed to investigate how MIRO proteins regulate mitochondrial dynamics in neurons. Mitochondria are essential for brain health, and their dysfunction is increasingly recognised as a central feature of numerous neurological disorders, including Parkinson’s disease (PD), ALS, and Alzheimer’s. The outer mitochondrial membrane MIROs are emerging as key regulators of mitochondrial homeostasis, being implicated in an ever-growing list of mitochondrial processes. Accordingly, this proposal hypothesises that MIROs act as mitochondrial adaptors that sense changes in the cellular environment and selectively engage with molecular machinery to maintain neuronal health. Despite their importance, the mechanisms by which MIROs coordinate their spectrum of interactions and functions remains unclear. To address this knowledge gap, MiroMap will: 1) define the MIRO interactome in neurons using in situ crosslinking and mass spectrometry, 2) identify factors that influence MIRO binding including neuronal activity and PD pathology, and 3) investigate how MIROs contribute to mitochondrial dynamics using spatial proteomics. To achieve these research objectives, MiroMap integrates cutting-edge techniques such as genetic code expansion and spatial proteomics with live-cell imaging and neuronal models. By uncovering how MIROs dynamically coordinate mitochondrial function in response to synaptic activity and pathological stimuli, MiroMap will generate foundational insight into the molecular mechanisms that underpin neuronal health and disease, with the potential to inform future therapeutic strategies targeting mitochondrial dysfunction in neurodegeneration. This fellowship will be hosted at UCL under the supervision of Prof. Josef Kittler, a leading expert in mitochondrial neurobiology. This environment provides the ideal platform to expand my expertise into neuroscience and develop the skills required to lead an independent research group.