Reconstructing the evolution of monoamines as neurotransmitters

单胺类化合物是神经递质分子中最重要的一类。在人类，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，如：情绪、记忆、血液流动、食欲、睡眠、认知等。单胺最经典的例子包括5-羟色胺、多巴胺和去甲肾上腺素，它们通常通过与一组被称为G-蛋白偶联受体(GPCRs)的受体偶联来发挥作用。它们是动物(包括人类)中最大的受体，也是一个重要的药理靶点。有趣的是，单胺和负责它们合成的酶不仅在不同的动物中被发现，而且在植物、真菌和一些细菌中也被发现。这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。到目前为止，还不清楚在动物进化过程中，单胺是如何以及何时获得神经元信号传递功能的，也不清楚为什么它们对神经元功能如此重要。因此，该奖学金的目标是在非双边动物中重建单胺能信号的进化。为了实现这一点，我将使用一系列广泛的计算和实验策略，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)是如何、何时以及为什么成为动物的神经递质的？”“单胺类物质作为神经递质的使用有多悠久？”“神经系统是如何进化的？”“单胺在神经元和神经系统进化中的作用是什么？”研究进化的最重要的动物群体之一是被称为“非双侧动物”的早期分化动物，它们包括海绵、水母、珊瑚和梳状水母等生物。这些动物被认为是在属于比拉特里亚的动物出现之前出现的，这些动物包括老鼠、鱼、苍蝇和人类等物种。非双边生物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，其中一些动物，如海绵和胎盘动物，完全缺乏神经系统或神经元。作为动物的祖先，非双边动物将让我们了解更复杂的动物的进化和发展。这一多学科研究金的目标与BBSRC未来的指令“推进生物科学的前沿：对生命规则的理解”和战略优先领域“数据驱动的生物学”保持一致。这项研究在基础科学方面具有令人兴奋的潜力，在生态学和保育等领域也有实际应用：已知的大多数非双边动物是海洋动物。它们中的一些具有极其重要的生态作用，如水母和珊瑚(蛇形目)。珊瑚礁为海洋动物提供了重要的生态系统，包括为当地通信和环境提供宝贵的海洋资源。珊瑚目前受到漂白、气候变化、风暴和入侵物种等过程的威胁，如棘冠海星(Acanthaster Planci)。了解细胞信号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：单胺通过激活GPCRs发挥作用，GPCRs是非常重要的药理靶点。目前仍有许多人类受体的配体尚未确定。重建这些受体的进化，包括非双边动物，将使我们能够更好地了解这些受体是如何在人类和动物身上出现和进化的，并有可能识别激活它们的配体。

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.