FLPing around aids behavioural adaptability in nematodes

线虫是动物王国中一个成功的故事，它们在数量上仅次于节肢动物。线虫的解剖结构非常简单——它们只有体壁上的纵向肌肉，它们的神经系统由大约300个神经细胞组成，这些细胞在整个门的物种中以相似的模式排列。尽管如此，它们是复杂的、多样化的、高度专业化的动物。事实上，它们成功的一个原因是它们行为的多样性，以及它们在世界各地许多不同栖息地生存的能力，既可以作为自由生活的物种，也可以作为寄生物种。根据它们的亲缘关系，线虫可以分为不同的支系——目前的思路是有五个主要支系（I-V）。作为牲畜寄生虫，线虫可显著影响农业动物的健康和福祉，从而直接影响生产力、经济回报和动物福利。例如，弯曲血蜱是绵羊中致病性最强的线虫，可导致严重贫血，有时甚至死亡。作为植物的寄生虫，线虫可以导致植物材料的完全破坏，并且是许多重要的商业作物，如马铃薯和西红柿等的一个重大问题。控制线虫寄生虫的一个关键问题是，随着线虫产生耐药性，目前用于治疗它们的药物正在变得不那么有效。事实上，在世界上的一些地区（例如苏格兰和新西兰的部分地区），由于寄生虫控制问题，羊和牛无法养殖。因此，我们需要寻找新的药物靶点，使畜牧业在英国和更远的地方都有一个未来。为了确保生存，线虫必须移动、觅食和繁殖。这些行为都依赖于肌肉，并受线虫神经系统内信号分子的控制。与结构不同，线虫神经系统的化学组成是复杂的。一组信号分子是神经肽。在线虫中，有三个主要的神经肽家族，其中最大的家族被称为fmrfamily -样肽或FLPs。FLP已被证明可以调节许多线虫物种的摄食、繁殖和运动，因此，FLP信号系统是一种潜在的新型药物候选靶点。线虫中有大约70个FLPs，在自由生活和寄生物种中也有相同的结构。我们不知道这些结构是否在不同种类的线虫中起着相似的作用。这些信息对于选择“最佳”候选药物靶标非常重要。例如，如果单个FLP对一种动物寄生虫的生存至关重要，但对另一种动物寄生虫却没有作用，那么它就没有在几种重要的线虫寄生虫中发挥重要作用的目标那么有吸引力。我们有一些初步的证据，指出在整个线虫门的FLPs功能差异。本研究计划通过检查它们在代表不同进化支系和生活方式的一系列线虫物种的神经系统中的分布，并探索FLPs对肌肉行为的影响，来研究单个FLPs在线虫中的作用。这项研究将增加我们对线虫中FLP信号系统的理解，比较分析将为FLP信号作为寄生虫控制目标系统的效用提供基线数据。

Nematodes are a success story in the Animal Kingdom and they are second only to the Arthropods in terms of numbers. The anatomy of a nematode is very simple - they only possess longitudinal muscles in their body wall and their nervous system comprises of ~300 nerve cells that are arranged in a similar pattern in species across the phylum. Despite this, they are complex, diverse and highly specialised animals. Indeed, one reason for their success is the diversity in their behaviour and their ability to survive in many different habitats throughout the world as both free-living and parasitic species. Nematodes can be divided into different clades based on their relatedness - the current train of thought is that there are five major clades (I-V). As parasites of livestock, nematodes can significantly impact the health and well-being of agricultural animals, thereby directly affecting productivity, economic return and animal welfare. For example, Haemonchus contortus is the most pathogenic nematode of sheep, leading to severe anaemia and sometimes death. As parasites of plants, nematodes can cause total destruction of plant material, and are a significant problem in many commercially important crops such as potato and tomato, amongst others. A key issue in the control of nematode parasites is that the drugs that are currently used to treat them are becoming less effective as the worms develop resistance. In fact, in some areas of the world (for example, parts of Scotland and New Zealand), sheep and cattle cannot be farmed simply because of parasite control problems. Therefore we need to search for novel drug targets so that livestock farming has a future both in the UK and further afield. In order to ensure survival a nematode must move, feed, and reproduce. Each of these behaviours rely on muscle, and are under the control of signalling molecules within the nervous system of the nematode. Unlike structure, the chemical make-up of the nematode nervous system is complex. One group of signalling molecules are the neuropeptides. In nematodes there are three main families of neuropeptides, the largest of which are known as the FMRFamide-like peptides or FLPs. FLPs have been shown to modulate feeding, reproduction and movement in many nematode species and therefore, the FLP signalling system is a potential novel drug target candidate. There are >70 FLPs in nematodes, and the same structures have been shown to be present in free-living and parasitic species. We don't know if these structures play similar roles in different nematode species. This information is important in order to select the 'best' candidates for drug targetting. For example, if an individual FLP was critical to the survival of one animal-parasite but not to another, then it would be a less attractive target than one that played an important role in several important nematode parasites. We have some preliminary evidence which points to functional differences in FLPs across the nematode phylum. This study plans to investigate the role of individual FLPs in nematodes by examining their distribution in the nervous system of a range of nematode species representing different clades and lifestyles and probing the effects of the FLPs on muscle-based behaviours. This research will increase our understanding of the FLP signalling system in nematodes, and comparative analyses will provide baseline data on the utility of FLP signalling as a target system for parasite control.