Logistic vulnerabilities of brain synapses
The Sun group investigates protein machines that manage the molecular logistics of brain synapses using quantitative spatial proteomics approaches.
The brain stores memories for decades, but the molecules in the brain do not last long. Instead, to process and store information with molecules, the brain synapses ‘consume’ molecules constantly. Molecular supply, therefore, puts constraints on synaptic function; and the logistic vulnerabilities of brain synapses can seed the onset of neurological diseases.
Research in the past decade has revealed a key feature of synaptic logistics strategy: decentralization. While genetic information is housed in the cell body, its transcripts and protein products that execute and regulate biomolecular processes are decentralized to synapses. For example, our recent findings reveal that the machinery for protein turnover, i.e. the synthesis and degradation of protein machines, is prevalent at neuronal synapses; and their local function adapts to local need. To investigate the local molecular logistics that enable synaptic function and plasticity, we use multiplex, quantitative, single-molecule localization to reveal the spatial proteomics in neuronal processes and synapses. We are particularly interested in protein machines that manage the molecular logistics of synapses, e.g. the protein synthesis and degradation machines, the transport machinery for ions, nutrients, and neurotransmitters, and the machinery involved in lipid and energy consumption. A quantitative, systems examination of the local synaptic logistics will reveal vulnerabilities that likely underlie neurological disorders, which currently has no cure.
Starting 2023, the Sun group will have projects available in single-molecule spatial proteomics as well as the molecular logistics of brain synapses for postdocs and Ph.D. students supported by Lundbeck Foundation. Please contact Chao directly at chaosun@dandrite.au.dk
