Reconstructing the evolution of monoamines as neurotransmitters

重建单胺作为神经递质的进化

• 批准号: BB/W010305/2
• 负责人: Luis Yanez Guerra
• 金额: $ 27.93万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW010305%2F2
• 关键词: Reconstructing; evolution; monoamines; neurotransmitters; Reconstructing; evolution; monoamines; neurotransmitters

The monoamines are one of the most important groups of neurotransmitter molecules. In humans, they are synthesized in the brain, nerve tissue and adrenal glands. These molecules help to regulate processes such as: emotions, memory, blood-flow, appetite, sleep, cognition and many more. The most classic examples of monoamines include serotonin, dopamine and noradrenalin, and they typically act through coupling to a group of receptors known as G-protein coupled receptors (GPCRs). They are the largest group of receptors in animals (including humans) and they are a significant pharmacological target. Intriguingly, monoamines and the enzymes responsible for their synthesis have been identified not only in different animals but also in plants, fungi and some bacteria. Indicating that the synthesis and occurrence of these neurotransmitter molecules predate the existence of the nervous system and neurons. To date, it is not clear how and when during animal evolution monoamines acquired their functions in neuronal signalling, and why they became so important for neuronal functions. Thus, the goal of this fellowship is to reconstruct the evolution of monoaminergic signalling in non-bilaterian animals. To achieve this, I will use a wide set of computational and experimental strategies that will allow me to answer very interesting key biological questions such as: "How, when, and why did the monoamines (present in plants and bacteria) become neurotransmitters in animals?" "How ancestral is the use of monoamines as neurotransmitters?" "How did the nervous system evolve"? "What is the role of monoamines in the evolution of neurons and nervous systems?"One of the most important groups of animals in which to study evolution are the early-diverging animals known as 'non-bilaterians', which comprise organisms such as sea sponges, jellyfish, corals, and comb-jellies. These animals are believed to have appeared before the emergence of animals belonging to the Bilateria-which include species such as mice, fish, flies, and humans. One of the main characteristics of the non-bilaterians is the lack of a brain or a complex centralised nervous system. In fact, some of them, such as the sponges and placozoans, completely lack a nervous system or neurons. Being an "ancestral" group of animals, the non-bilaterians will allow us to understand the evolution and development of more complex animals. The aims of this multidisciplinary fellowship align with the BBSRC's future directive of "Advancing the frontiers of bioscience: Understanding of the rules of life" and the strategic priority area "Data driven biology". This research has exciting potential for breaking new ground in fundamental science, and also for practical applications in fields such as:Ecology and conservation: Most of the known non-bilaterian animals are marine animals. Some of them have extremely important ecological roles, such as the jellyfish and corals (Cnidarians). Coral reefs provide an important ecosystem for marine animals, including valuable marine resources for local communicates and environments. Corals are currently threatened by processes such as bleaching, climate change, storms and invasive species such as the crown-of-thorns starfish (Acanthaster planci). Understanding the processes involved in cellular signalling and cell communication will help to understand and predict their behaviour, reproduction and conservation. Neurosciences and medicine: Monoamines act through the activation of GPCRs, which are very important pharmacological targets. There are still many human receptors for which no ligands have been identified. Reconstructing the evolution of these receptors including non-bilaterian animals will allow us to better understand how these receptors appeared and evolved in humans animals and potentially identify the ligands that activate them.

单胺是最重要的神经递质分子之一。在人类中，它们是在大脑，神经组织和肾上腺中合成的。这些分子有助于调节过程，例如：情绪，记忆，血液，食欲，睡眠，认知等等。单胺的最经典例子包括5-羟色胺，多巴胺和去甲肾上腺素，通常通过偶联与一组称为G蛋白偶联受体（GPCRS）的受体作用。它们是动物（包括人类）中最大的受体组，它们是重要的药理靶标。有趣的是，单胺和负责其合成的酶不仅在不同的动物中，而且在植物，真菌和某些细菌中被鉴定出来。表明这些神经递质分子的合成和发生早于神经系统和神经元的存在。迄今为止，目前尚不清楚动物进化过程中如何以及何时获得其在神经元信号中的功能，以及为什么它们对神经元功能如此重要。因此，该团契的目的是重建非副脑动物中单胺能信号传导的演变。为了实现这一目标，我将使用各种计算和实验策略，使我能够回答非常有趣的关键生物学问题，例如：“单胺（存在于植物和细菌中）如何，何时以及为什么会成为动物中的神经递质？” “将单胺用作神经递质的祖先如何使用？” “神经系统如何发展”？ “单胺在神经元和神经系统的进化中的作用是什么？”最重要的动物群体之一是研究进化的动物，是被称为'非比利植物的早期动物'，其中包括海绵，海绵，水母，珊瑚，珊瑚和梳子般的生物体。据信这些动物在属于双肌植物的动物出现之前就出现了，其中包括小鼠，鱼类，苍蝇和人类。非副手的主要特征之一是缺乏大脑或复杂的集中神经系统。实际上，其中一些人，例如海绵和斑点，完全缺乏神经系统或神经元。作为“祖先”的动物群体，非生物学家将使我们能够了解更复杂的动物的进化和发展。这一多学科奖学金的目的与BBSRC的未来指令“推进生物科学的前沿：对生命规则的理解”和战略优先领域“数据驱动生物学”。这项研究具有打破基本科学的新基础的令人兴奋的潜力，以及在诸如生态和保护之类的领域的实际应用：大多数已知的非比利群动物都是海洋动物。其中一些具有极为重要的生态作用，例如水母和珊瑚（Cnidarians）。珊瑚礁为海洋动物提供了重要的生态系统，包括用于当地交流和环境的宝贵海洋资源。目前，珊瑚受到漂白，气候变化，风暴和侵入性物种等过程的威胁。了解细胞信号传导和细胞通信中涉及的过程将有助于理解和预测其行为，繁殖和保护。神经科学与医学：单胺通过GPCR的激活来起作用，GPCR是非常重要的药理靶标。仍然有许多人类受体，没有发现配体。重建这些受体的演变在内，包括非生物动物将使我们能够更好地了解这些受体如何在人类动物中出现和进化，并有可能识别激活它们的配体。