Abstract
In neurons, Ribonuclear Proteins (RNPs) such as Staufen2 play a vital role in mRNA transport for local translation, contributing to axon guidance and synaptic plasticity [1,2]. Here we aim to explore this interaction by tissue engineering a network of neurons using growth factor loaded nanoneedles to guide and differentiate pluripotent stem cells to a defined neural cluster [3,4]. The network will allow local manipulation of neuronal activity and RNP dynamics to elucidate how Staufen2 contributes to synaptic functions and neuronal network behaviour. The project will blend areas of molecular, cell and theoretical biology with nano and material sciences in bioengineering.
References
[1] Sugimoto, Yoichiro & M Chakrabarti, Anob & Luscombe, Nicholas & Ule, Jernej. (2017). Using hiCLIP to identify RNA duplexes that interact with a specific RNA-binding protein. Nature Protocols. 12. 611-637. 10.1038/nprot.2016.188.
[2] Heraud, Jacki & Sharangdhar, Tejaswini & Li, Xiao & Pfeifer, Philipp & Tauber, Stefanie & Orozco, Denise & Hörmann, Alexandra & Thomas, Sabine & Bakosova, Anetta & Farlow, Ashley & Edbauer, Dieter & Lipshitz, Howard & D Morris, Quaid & Bilban, Martin & Doyle, Michael & Kiebler, Michael. (2013). Staufen2 Regulates Neuronal Target RNAs. Cell reports. 5. 10.1016/j.celrep.2013.11.039.
[3] Chiappini, Ciro & De Rosa, Enrica & Martinez, Jonathan & Liu, Xue & Steele, Joseph & Stevens, M.M. & Tasciotti, Ennio. (2015). Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization. Nature materials. 14. 10.1038/nmat4249.
[4] Hsu, Chia-Chen & Serio, Andrea & Amdursky, Nadav & Besnard, Cyril & M. Stevens, Molly. (2018). Fabrication of Hemin-Doped Serum Albumin-Based Fibrous Scaffolds for Neural Tissue Engineering Applications. ACS Applied Materials & Interfaces. 10. 10.1021/acsami.7b18179.