Periodic Reporting for period 1 - AURORA (An integral solution for quantifying intracellular lipid transport using close to native lipid probes.)
Periodo di rendicontazione: 2024-01-01 al 2025-06-30
The overall objective of the project was to set the stage for the commercialization of the lipid imaging platform that the Nadler lab has developed over the last decade. This technology, which is based on photoactivatable lipid probes, allows to visualize lipids (fats) in mammalian cells using fluorescence mircoscopy and now enables studies of the roles of lipids in cell biology in unprecedented detail. During the course of the AURORA project, we adapted our approach to a high-throughput setting, developed new strategies for data analysis, explored routes for efficient procurment of building blocks and investigated the possibilty of pharmacological interventions into cellular lipid trafficking pathways.
The primary effort of the project was aimed at miniaturizing and automatizing the lipid imaging workflow. To this end we developed (i) a new photoreactor prototype, which fulfills the main criteria with regard to performance and safety to serve as a blueprint for a commercial solution; we adapted (ii) the lipid imaging workflow to a 384 well screening format and confirmed that it is compatible with high-throughput microscopy; we worked together with the company Motius to (iii) develop the outline of a potential commercial image analysis software; we performed initial pharmacological interventions and (iv) demonstrated specific effects of drug treatment on the intracellular transport of individual lipid species. The approaches developed will be crucial for eventual commercialization and also helped the publication of a number of high-impact publications and well-received preprints.
In essence, we have developed a pipeline for studying the role of lipids in cell biology. Given the importance of lipids for health and disease – there are hundreds of hereditary diseases and most major lifestyle and neurodegeneritive diseases have a lipid component – the potential benefits for society can be large. What is needed to demonstarte usefuleness for the non-academic marked (pharma) is a clear case demonstration with regard to elucidating a disease mechanism, something we are currently actively working on.