Delivering the impossible - novel fatty acid delivery reagents to enable in vivo research and discovery

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Fatty acid metabolism is an essential process common to all life, with fatty acids being both core components of cellular membranes and key regulators of protein function through fatty acid-based post-translational modifications such as S-acylation. Understanding fatty acid metabolism is also fundamental to many areas of biotechnological, health or industrial interest such as biofuels, plant seed oils, dietary fat composition, type-I diabetes, prostaglandin production or lipid storage diseases. The direct study of S-acylation in eukaryotes, outside of a very limited number of cell cultures, is blocked by the lack of effective research tools to incorporate, monitor and trace fatty acids. The broader fatty acid metabolism communities also urgently need resources to enable timely research progression and new ways of experimentation. With a focus on S-acylation in plants, this interdisciplinary work will combine existing validated knowledge to produce effective reagents for in vivo delivery of click-chemistry enabled fatty acid alkyne probes. Using Arabidopsis, we will validate these new reagents by profiling the dynamics of protein S-acylation and examining the plant secreted acylated proteome, a hitherto inaccessible area of cell-to-cell signalling in plants. In addition, through committed international collaborators, we will deploy these novel reagents to other recalcitrant systems such as mammalian primary cell cultures, intact organs and tissues. Following validation, we will make reagents freely available to the research community to assess utility across the wider fatty acid metabolism field. These universally applicable tools will service unmet global needs and enable fatty acid research across a far wider range of organisms and systems than is currently possible, delivering international impact, exceptional value for money and support BBSRC "technology development for the biosciences" priority.