https://video.igem.org/videos/watch/9477f612-ad72-4bc6-869f-eaaf4be223e7 Title: BRIDGE: Brain Repair via Injury-Induced BDNF Delivery Description: Every year, countless stroke survivors lose the freedom to walk and live independently. Damaged neurons struggle to repair themselves, and conventional drugs often cannot cross the blood–brain barrier to reach the injury site. Meet BRIDGE — our engineered system that uses synNotch to deliver brain-derived neurotrophic factor (BDNF) precisely where it is needed. In this video, we walk through how BRIDGE works: LAB: We built a BCAN-sensing synNotch receptor with three components — an anti-BCAN scFv, the synNotch core, and a GAL4-VP64 transcription factor — to drive BDNF expression. After detecting background activation in HEK293T cells, we redesigned the circuit in Jurkat cells and validated it with GFP fluorescence, flow cytometry, luciferase assays, and ELISA. Guided by modeling, we engineered scFv mutations (e.g., D93A) that reduce background leakage while preserving injury-site responsiveness. MODEL: Stochastic simulations of the synNotch pathway and Sobol sensitivity analysis identified the Hill coefficient as the key lever for BDNF output, while docking and interface-energy ranking predicted a 36 pM BCAN–scFv affinity and shortlisted five scFv mutants for testing. HUMAN PRACTICE: Following our SIKQ-GET framework (FIAQA, PEI, IPM), we consulted health authorities, researchers, and the public across three rounds, and shared science with nearly 1,000 people through rural outreach, specimen-museum courses, lab open days, and online communities. Our results provide an initial proof of concept for localized neurotrophic support after brain injury. Because both its sensor and its therapeutic payload can be replaced, BRIDGE could one day grow beyond stroke rehabilitation into a broader platform for precisely controlled treatment across central nervous system disorders. Step by step, we hope to turn a promising laboratory design into a safe, practical, and accessible bridge — from brain injury to recovery. Wiki | Official Page Thu, 29 Oct 2026 22:23:06 GMT https://validator.w3.org/feed/docs/rss2.html PeerTube - https://video.igem.org https://video.igem.org/client/assets/images/icons/icon-1500x1500.png https://video.igem.org/videos/watch/9477f612-ad72-4bc6-869f-eaaf4be223e7 All rights reserved, unless otherwise specified in the terms specified at https://video.igem.org/about and potential licenses granted by each content's rightholder.