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

脂肪酸是所有生物的重要组成部分，是脂肪和油的主要成分。它们也是每个细胞功能的关键组成部分。每个细胞都使用膜脂中的脂肪酸，并利用它们来改变细胞内蛋白质的功能或作用。我们特别感兴趣的是了解脂肪酸是如何以这种方式在植物中被利用的，这一过程被称为s -酰化。最近，一些看起来像脂肪酸但带有反应性炔“手柄”的化学工具被证明在给予某些细胞类型时表现得像正常脂肪酸。炔手柄可以让研究人员分离出附着在脂肪酸上的蛋白质，并对它们进行特定的分析。不幸的是，这种方法在有限数量的特定细胞类型之外不起作用。这可能是因为大多数细胞不能吸收提供给它们的脂肪酸。在植物中尤其如此，因为它们不需要从外界环境中吸收脂肪酸，因为它们可以自己制造脂肪酸。更糟糕的是，脂肪酸的化学性质意味着它们也不溶于水，这减少了每次实验中可以给予的剂量。这反过来又降低了实验检测带有脂肪酸的蛋白质的灵敏度。在这个项目中，我们的目标是制造具有炔柄的脂肪酸，它更容易溶解，使它们不需要生物体的任何努力就能进入细胞。这使用了20世纪80年代的验证思想，结合了尖端的化学技术。使用这些化学工具，我们将能够研究不同生物体中涉及脂肪酸的广泛过程。我们还将与其他研究人员分享我们的工具，使他们能够在他们感兴趣的生物体中进行以前不可能的脂肪酸代谢实验。

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.