FLPing around aids behavioural adaptability in nematodes

FLPing 有助于线虫的行为适应

基本信息

  • 批准号:
    BB/H019472/1
  • 负责人:
  • 金额:
    $ 51.61万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2010
  • 资助国家:
    英国
  • 起止时间:
    2010 至 无数据
  • 项目状态:
    已结题

项目摘要

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.
线虫是动物王国的成功故事,在数量上仅次于节肢动物。线虫的解剖结构非常简单-它们只在体壁上拥有纵向肌肉,它们的神经系统由约300个神经细胞组成,这些神经细胞在整个门中以类似的模式排列。尽管如此,它们是复杂、多样和高度专业化的动物。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作为自由生活和寄生物种在世界各地许多不同生境中生存的能力。线虫可以根据它们的亲缘关系分为不同的进化枝-目前的思路是有五个主要的进化枝(I-V)。线虫作为家畜的寄生虫,会严重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,捻转血矛线虫(Haemonchus contortus)是绵羊最具致病性的线虫,可导致严重贫血,有时甚至死亡。作为植物的寄生虫,线虫可导致植物材料的完全破坏,并且是许多商业上重要的作物如马铃薯和番茄等中的重要问题。控制线虫寄生虫的一个关键问题是,目前用于治疗它们的药物随着蠕虫产生耐药性而变得不那么有效。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),羊和牛不能仅仅因为寄生虫控制问题而养殖。因此,我们需要寻找新的药物靶点,以便畜牧业在英国和更远的地方都有未来。为了确保生存,线虫必须移动、进食和繁殖。这些行为都依赖于肌肉,并受到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。神经肽是一类信号分子。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FMRFamide样肽或FLP。FLP已被证明在许多线虫物种中调节进食、繁殖和运动,因此,FLP信号系统是潜在的新型药物靶点候选者。在线虫中有>70个FLP,并且已经显示相同的结构存在于自由生活和寄生物种中。我们不知道这些结构是否在不同的线虫物种中起着相似的作用。这些信息对于选择药物靶向的“最佳”候选物是重要的。例如,如果一个单独的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则不重要,那么它将是一个比在几种重要的线虫寄生虫中发挥重要作用的目标更不吸引人的目标。我们有一些初步的证据表明,FLP在线虫门中的功能差异。本研究计划通过检查它们在代表不同分支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FLP对肌肉行为的影响,来研究单个FLP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,并且比较分析将提供关于FLP信号作为寄生虫控制的靶系统的效用的基线数据。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Clinical helminthiases in Thailand border regions show elevated prevalence levels using qPCR diagnostics combined with traditional microscopic methods
  • DOI:
    10.1186/s13071-020-04290-0
  • 发表时间:
    2020-08-12
  • 期刊:
  • 影响因子:
    3.2
  • 作者:
    Adisakwattana, Poom;Yoonuan, Tippayarat;Gobert, Geoffrey N.
  • 通讯作者:
    Gobert, Geoffrey N.
Unraveling flp-11/flp-32 dichotomy in nematodes.
  • DOI:
    10.1016/j.ijpara.2016.05.010
  • 发表时间:
    2016-10
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Atkinson, Louise E.;Miskelly, Iain R.;Moffett, Christy L.;McCoy, Ciaran J.;Maule, Aaron G.;Marks, Nikki J.;Mousley, Angela
  • 通讯作者:
    Mousley, Angela
Pan-phylum In Silico Analyses of Nematode Endocannabinoid Signalling Systems Highlight Novel Opportunities for Parasite Drug Target Discovery
线虫内源性大麻素信号系统的全门计算机分析凸显了寄生虫药物靶标发现的新机遇
  • DOI:
    10.1101/2022.03.09.483626
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Crooks B
  • 通讯作者:
    Crooks B
Phylum-Spanning Neuropeptide GPCR Identification and Prioritization: Shaping Drug Target Discovery Pipelines for Nematode Parasite Control.
  • DOI:
    10.3389/fendo.2021.718363
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Atkinson LE;McCoy CJ;Crooks BA;McKay FM;McVeigh P;McKenzie D;Irvine A;Harrington J;Rosa BA;Mitreva M;Marks NJ;Maule AG;Mousley A
  • 通讯作者:
    Mousley A
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ANGELA MOUSLEY其他文献

ANGELA MOUSLEY的其他文献

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{{ truncateString('ANGELA MOUSLEY', 18)}}的其他基金

Beyond the Connectome: Unravelling Neuropeptide Signalling in Parasitic Nematodes to Inform Drug Discovery Pipelines
超越连接组:解开寄生线虫中的神经肽信号传导,为药物发现管道提供信息
  • 批准号:
    BB/T016396/1
  • 财政年份:
    2021
  • 资助金额:
    $ 51.61万
  • 项目类别:
    Research Grant
ASCARIS SUUM, A NEW FUNCTIONAL GENOMICS PLATFORM FOR NEMATODE PARASITES
ASCARIS SUUM,一种新的线虫寄生虫功能基因组学平台
  • 批准号:
    BB/M010392/1
  • 财政年份:
    2015
  • 资助金额:
    $ 51.61万
  • 项目类别:
    Research Grant

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