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

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Fatty acids are essential parts of all living things and form the main part of fats and oils. They are also key components of the function of every cell. Every cell uses fatty acids in their membrane lipids and also uses them to alter the function or role of proteins within the cell. We are particularly interested in understanding how fatty acids are used in this way in plants in a process called S-acylation.Recently, some chemical tools that look like fatty acids but have a reactive alkyne "handle" attached, were shown to behave like normal fatty acids when given to some cell types. The alkyne handle allows researchers to isolate proteins which are attached to that fatty acid and perform specific analysis on them. Unfortunately, this method does not work outside of a limited number of specific cell types. This is probably because most cells aren't able to take up fatty acids that are supplied to them. This is particularly true in plants where there is no need to absorb fatty acids from the outside environment as they can make their own. To make matters worse, the chemical nature of fatty acids means that they are also not soluble in water which reduces the dose that can be given in each experiment. This in turn reduces the sensitivity of the experiment to detect proteins with fatty acids attached.In this project we aim to make fatty acids with alkyne handles that are more soluble enabling them to get inside the cell without any effort on the part of the organism. This uses validated ideas from the 1980's coupled to cutting edge chemical technology. Using these chemical tools, we will be able to investigate a wide range of processes involving fatty acids in different organisms. We will also share our tools with other researchers to enable them to do previously impossible experiments on fatty acid metabolism in their organisms of interest.