Serio Seed Grant (360G-Wellcome-213949_Z_18_Z)
Amyotrophic Lateral Sclerosis (ALS) is an incurable fatal disease that affects principally Motor Neurones (MNs). Interestingly, spinal MNs have extremely long axons, which makes them particularly reliant on efficient decentralized protein translation and axonal transport. We have evidence that ALS presents characteristics of distal axonopathies, with defects in axonal transport, protein homeostasis and changes in local axonal translation reported. Moreover, most ALS-mutations often directly affect RNA processing. Against this background, understanding the links between axonal length and RNA compartmentalisation could highlight new potential therapeutic avenues. Induced pluripotent stem cells (iPSCs) have proven extremely useful in studying ALS; however, the question of how axonal length affects RNA compartmentalisation in MNs cannot be systematically addressed with current in vitro paradigms, as they do not provide efficient ways to control axonal length. I will develop a platform to study how axonal length in iPSC MNs influences local mRNA translation and RNA compartmentalisation, combiningimaging and transcriptomic analysis with bioengineered alignment substrates that allow to obtain ordered arrays of very long axons in vitro.With this platform I will conduct a pilot study on axonal compartment -specific transcriptomics in MNs and analyse the effect of ALS-mutations on local translation in long motor axons
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Grant Details
Amount Awarded | 99987 |
Applicant Surname | Serio |
Approval Committee | Science Seeds Advisory Panel |
Award Date | 2018-09-06T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Seed Award in Science |
Internal ID | 213949/Z/18/Z |
Lead Applicant | Dr Andrea Serio |
Partnership Value | 99987 |
Planned Dates: End Date | 2021-05-20T00:00:00+00:00 |
Planned Dates: Start Date | 2018-11-20T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |