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MSL Seminar Series: November – Invited Speaker, Dr. Joachim Rädler
November 20, 2024 @ 3:00 pm - 4:00 pm
Invited Speaker:
Dr. Joachim Rädler
Faculty of Physics and Center for NanoScience, Ludwig-Maximilians-Universität München
This seminar will be presented in a hybrid format. Audience members are welcome to attend either in person at the MSL lecture theatre (room 102) or via the zoom link. Those connecting via zoom will be able to ask questions during the Q&A portion using the chat function.
Host: Dr. Sabrina Leslie
Zoom registration link: https://ubc.zoom.us/meeting/register/u5ModemsqD4jHNZl1Jag2qeh3puCEkluBlV4
Talk title: A biophysics view on ionizable lipid mesophases and systems biology inspired self-regulating gene delivery
Abstract: Lipid Nanoparticles (LNPs) represent the most advanced technology for delivery of nucleic acid. Understanding the structure-activity relation is key to rationalize next generation LNP formulations. We discuss the distinct role of pH dependent structural transitions in bulk phases of cationic ionizable lipids (CILs). Using high resolution small angle X-ray scattering we find pH-driven transitions from inverse spherical micellar cubic (Fd3m) to inverse hexagonal (HII) phases. These structural transitions are shown to correlate with gene delivery timing assessed from single cell GFP expression time courses. To yield high throughput data we introduce live cell imaging on single cell arrays (LISCA) and extract distribution functions of mRNA expression onset times, efficiency and mRNA stability using mathematical modeling of LNP-based mRNA delivery. This paves the way for application of more sophisticated gene regulatory motives. We show that combined siRNA/mRNA LNPs implement a feed forward loop with faster and noise-reduced expression. Using the example of reprogrammed migratory phenotypes we discuss how multiplexed RNA delivery could develop into a quantitative tool for transient synthetic biology.
