Current lines of research:
ARC as a molecular hub for decoding long-term synaptic plasticity
How does ARC work?
ARC is the product of an immediate early gene and a multifunctional protein implicated in diverse forms of synaptic plasticity, postnatal cortical development, and memory formation. ARC functions as a protein interaction hub linking synaptic activity, intracellular trafficking, and gene expression programs with both synaptic and nuclear roles. It self-associates to form stable oligomers, including retrovirus-like capsids that mediate intercellular signaling.
Our work aims to elucidate ARC trafficking, assembly, and molecular functions, and to apply this knowledge to decode how plasticity is logically implemented at the neural systems level.
Decoding the molecular logic of ARC is increasingly relevant to brain disease. ARC signaling and plasticity mechanisms are implicated in Alzheimer鈥檚 disease, neurodevelopmental disorders, and substance use disorders.
Gene expression regulation and translational control of synaptic plasticity
How are specific forms of translation orchestrated at synapses?
Previous work has identified BDNF as a key trigger for transcription- and translation-dependent synaptic plasticity in the adult brain. Current studies focus on mechanisms of selective mRNA translation in vivo, including activity-dependent remodeling of the 5鈥 mRNA cap-binding complex and regulation of small ribosomal subunit scanning during synaptic modification.
Methods
Our methodological strategy is designed to link activity鈥慸ependent molecular events to synapse鈥 and circuit鈥憀evel plasticity in intact brain tissue. The Bramham lab integrates complementary approaches across molecular, cellular, and systems neuroscience to dissect ARC鈥慸ependent synaptic plasticity. These include:
- In vivo electrophysiology in rodents, combined with genetic, viral, and pharmacological manipulations, to uncover molecular mechanisms of plasticity in defined circuits, cell types and synapses
- Biochemical and proteomic analyses of native protein鈥損rotein interactions and post鈥憈ranslational modifications
- Advanced imaging approaches, including single鈥憁olecule localization microscopy and particle tracking in neuronal cultures, as well as two鈥憄hoton and FRET imaging in hippocampal tissue slices
- Nanobody鈥慴ased tools for imaging and functional modulation of endogenous proteins
- Recombinant protein expression and purification for biophysical and structural studies
Funding
Top Research (Toppforsk) grant from the Research Council of Norway on the Arc protein. In collaboration with Prof. Jan Haavik, Prof. Petri Kursula, and Prof Aurora Martinez in the Department of Biomedicine, 黑料吃瓜资源.
EU H2020 Joint Programme in Neurodegenerative Disorders. 鈥淪ynaptic circuit protection in Alzheimers鈥檚 disease (AD) and Huntingtion鈥檚 disease (HD): BDNF/TrkB and Arc signaling as rescue factors鈥. Homepage:
Live two-photon excitation imaging of dentate granule cells transduced with fluorescent protein (YPet2) by single-cell electroporation in organotypic rat hippocampal slice-cultures.