Synaptosome on Chip (SyonChip): combining stem cell technologies, bioengineering and advanced molecular analysis to model the tripartite synapse in vitro

Andrea Serio (primary)
Tissue Engineering and Biophotonics
King's College London
Rickie Patani (secondary)
Institute of Neurology
University College London

Abstract

Over 100 trillion synapses exist within a human nervous system. Local transcriptional changes orchestrate fundamental processes within each synapse. Recently, astrocytes emerged as a vital partner in establishing and maturing synapses, adding an additional layer of complexity, defined as the tripartite synapse. iPSC technology and advances in stem cell biology permit the generation of in vitro models of glial-neuronal interaction, and yet a functional model of astrocyte-neuronal interaction influencing the local synapse transcriptome is not available. This project takes advantage of bioengineering techniques, microfabrication and stem cell biology to generate the first human in vitro model of the tripartite synapse.


References

1. Hall CE, Yao Z, Choi M, Tyzack GE, Serio A, Luisier R, Harley J, Preza E, Arber C, Crisp SJ, Watson PMD, Kullmann DM, Abramov AY, Wray S, Burley R, Loh SHY, Martins LM, Stevens MM, Luscombe NM, Sibley C, Lakatos A, Ule J, Gandhi S, Patani R. ‘Progressive motor neuron pathology and the role of astrocytes in a human stem cell model of VCP-related ALS’. Cell Reports 2017 (Accepted)

2. Serio, A. et al. Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy. Proc Natl Acad Sci U S A 110, 4697–4702 (2013).

3. Chung, W.-S., Allen, N. J. & Eroglu, C. Astrocytes Control Synapse Formation, Function, and Elimination. Cold Spring Harbor perspectives in biology 7, (2015).

4. Eroglu, C. & Ben A Barres. Regulation of synaptic connectivity by glia. Nature 468, 223–231 (2010).


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyNeurobiology
Techniques & Approaches
BioinformaticsEngineeringMicroscopy / ElectrophysiologyMolecular Biology