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

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.

单胺类是神经递质分子中最重要的一类。在人类中，它们在大脑、神经组织和肾上腺中合成。这些分子有助于调节过程，如：情绪，记忆，血液流动，食欲，睡眠，认知等等。单胺的最经典的例子包括血清素、多巴胺和去甲肾上腺素，它们通常通过与一组称为G蛋白偶联受体（GPCR）的受体偶联而起作用。它们是动物（包括人类）中最大的受体群，是重要的药理学靶标。有趣的是，不仅在不同的动物中，而且在植物、真菌和一些细菌中，都发现了单胺和负责合成单胺的酶。表明这些神经递质分子的合成和出现早于神经系统和神经元的存在。迄今为止，尚不清楚在动物进化过程中，单胺是如何以及何时获得它们在神经元信号传导中的功能，以及为什么它们对神经元功能变得如此重要。因此，本研究的目标是重建非双侧动物单胺能信号的演变。为了实现这一目标，我将使用一系列广泛的计算和实验策略，这些策略将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，何时以及为什么成为动物的神经递质？““单胺作为神经递质的用途有多古老？“神经系统是如何进化的？”单胺在神经元和神经系统的进化中起什么作用？“研究进化的最重要的动物群体之一是被称为‘非两侧对称’的早期分化动物，其中包括海绵、水母、珊瑚和梳状水母等生物。这些动物被认为是在两侧对称动物出现之前出现的，两侧对称动物包括老鼠、鱼、苍蝇和人类。非两侧对称的主要特征之一是缺乏大脑或复杂的中枢神经系统。事实上，其中一些，如海绵和盘形动物，完全缺乏神经系统或神经元。作为动物的“祖先”群体，非两侧对称动物将使我们能够了解更复杂动物的进化和发展。这个多学科奖学金的目标与BBSRC的未来指令“推进生物科学的前沿：了解生命的规则”和战略优先领域“数据驱动的生物学”相一致。这项研究具有令人兴奋的潜力，可以在基础科学领域开辟新的领域，也可以在以下领域进行实际应用：生态学和保护：大多数已知的非两侧对称动物是海洋动物。其中一些具有极其重要的生态作用，如水母和珊瑚（刺胞动物）。珊瑚礁为海洋动物提供了重要的生态系统，包括对当地交通和环境有价值的海洋资源。珊瑚目前受到漂白、气候变化、风暴和棘冠海星（刺海星）等入侵物种的威胁。了解细胞信号传导和细胞通讯的过程将有助于理解和预测它们的行为，繁殖和保护。神经科学和医学：单胺类通过激活GPCR发挥作用，GPCR是非常重要的药理学靶点。仍有许多人受体尚未鉴定出配体。重建这些受体的进化，包括非双侧性动物，将使我们能够更好地了解这些受体是如何在人类动物中出现和进化的，并可能识别激活它们的配体。