Localised mRNA translation rapidly remodelling distal cytoplasmic projections and autonomous glial-neuronal interactions

Host: Professor Jason Swedlow

Venue: MSI Small Lecture Theatre, SLS

In-Person Discovery Seminar

This seminar is fully funded by external sources.

Cells must rapidly regulate distinct peripheral projections autonomously within the same cytoplasm. Transcription alone cannot explain such regulation. mRNA transport and local translation are attractive mechanism to autonomously regulate the peripheral cytoplasm, independently of the cell nucleus. We are studying these processes in the most extremely polarised cells within an intact tissue, namely glia and neurones. Glial cells, like neurones, have long cytoplasmic projections that contact many other glial cells and multiple different neurones. These projections are known to be rapidly remodelled in response to neuronal activity and signalling events, crucial for nervous system function. We are using two systems: developing Drosophila larval motoneurons and surrounding glia undergoing subtle remodelling; and adult brain circadian master-clock PDF neurones and astrocytes undergoing dramatic daily light/dark-dependent cytoplasmic extension/retraction. We have already identified many examples of disease-linked localised mRNAs with remodelling functions in glia and neurons of both systems, encoding membrane/cytoskeletal regulators or junctional proteins and mRNA binding proteins required. Many of these transcripts are required for correct glial-neuron connections, neuronal plasticity and behaviour. We are using diverse interdisciplinary methodologies, including spatial transcriptomics, live super-resolution and single-molecule imaging. Our work has not only uncovered novel general principles of how the periphery of cells are regulated autonomously of the cell nucleus. It also provides candidate explanations for various poorly understood glial/neuronal-based diseases.