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Origins of Biology: How energy flow structures metabolism and heredity at the origin of life

生物学的起源：生命起源时能量流如何构建新陈代谢和遗传

基本信息

批准号：
BB/V003542/1
负责人：
Nick Lane
金额：
$ 307.32万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FV003542%2F1
关键词：
Origins Biology How energy flow

项目摘要

The origin of life is one of the most iconic questions in science. Work over decades has seemingly made good progress in synthesizing the basic building blocks of life under purportedly 'prebiotic' conditions. These building blocks include the nucleotides that make up the genetic material in DNA. However, there is a serious disconnect between this prebiotic chemistry and the actual biochemistry of known cells in almost every respect. To close this gap between geochemistry and biochemistry and elucidate the fundamental rules of life, we propose a different approach to the problem, grounded in life itself.We take as our starting point an important rule of life - energy flow across membranes. This feature of life is as deeply conserved across the tree of life as the genetic code itself. Yet while the importance of energy flow in biology cannot be overstated, the origin and evolutionary implications of the specific mechanism involved - the flow of protons (hydrogen ions) across membranes - has historically been neglected. Recent work on reconstructing the properties of the earliest cells is now opening up new possibilities. Our overarching hypothesis is that the flow of protons across membranes can drive the difficult reaction between carbon dioxide and hydrogen gas to form the carbon 'skeletons' that are used to make all the other building blocks of cells. We propose that analogous processes can be driven in structured prebiotic environments such as hydrothermal vents, giving rise to the familiar metabolism and biochemistry of cells. In particular, we hypothesize that genetic information first arose in this setting. Genetic heredity is strictly another form of growth, in which a genetic template is repeatedly copied (doubled) and passed on. We propose that its mysterious origins (which have resisted interpretation over decades, despite many clues) can best be understood in the context of actively growing protocells, driven by energy flow through a structured environment.We will explore this fundamental organizing principle: energy flow across barriers drives the synthesis of organic molecules - growth - and the building blocks needed for genetic heredity. Our specific objectives are to: (i) understand the driving force for growth; (ii) use biology as a guide to protometabolism; and (iii) resolve the origins of the genetic code in protocells. We have previously detailed possible mechanisms. In this grant, we will rigorously model the steps going from a strictly inorganic but structured setting (such as geologically sustained proton gradients across inorganic barriers in hydrothermal systems) to the formation of simple protocells with a rudimentary form of heredity, and finally to the emergence of true genetic heredity in protocells. We will test the predictions of this computational modelling experimentally, using a combination of microfluidic reactors and screening of possible prebiotic conditions based on the chemistry of cells. We will feedback the results of experiments into the models to refine our concepts and ultimately deliver a coherent, integrated understanding of the energetic rules of life. Our extensive pilot data gives strong credence to the work proposed here.We believe these rules will help to elucidate the forces that drive life into existence on a geologically active but sterile planet. We are primarily interested in understanding the rules that govern the emergence of life but our work also hasimplications for the search for life elsewhere in the universe, guiding future space exploration. At home, this work has vital implications for understanding the structure of our own metabolism, potentially elucidating both normal and altered patterns of metabolic flux in lifelong health and disease. Finally, fixing carbon dioxide as organic molecules using a biomimetic form of energy flow could facilitate carbon capture to produce synthetic gasoline, giving a net zero-emissions solution to energy security.

生命的起源是科学中最具标志性的问题之一。在所谓的“益生元”条件下，几十年来的工作似乎在合成生命的基本组成部分方面取得了良好进展。这些构件包括构成DNA遗传物质的核苷酸。然而，这种益生元化学与已知细胞的实际生物化学之间几乎在每个方面都存在严重的脱节。为了缩小地球化学和生物化学之间的差距，阐明生命的基本规律，我们提出了一种基于生命本身的不同方法来解决这个问题。我们以生命的一个重要规律——能量跨膜流动作为起点。生命的这一特征就像遗传密码本身一样，在整个生命之树上被深深保存下来。然而，尽管能量流在生物学中的重要性怎么强调都不为过，但它所涉及的特定机制——质子（氢离子）跨膜流动——的起源和进化意义一直被忽视。最近重建最早细胞特性的工作正在开辟新的可能性。我们的首要假设是，质子穿过膜的流动可以驱动二氧化碳和氢气之间的艰难反应，形成碳“骨架”，用于制造细胞的所有其他构建块。我们提出类似的过程可以在结构良好的益生元环境中驱动，如热液喷口，从而产生熟悉的细胞代谢和生物化学。特别是，我们假设遗传信息首先出现在这种情况下。基因遗传严格来说是生长的另一种形式，基因模板被反复复制（加倍）并传递下去。我们提出，其神秘的起源（尽管有许多线索，但几十年来一直难以解释）可以在活跃生长的原始细胞的背景下得到最好的理解，这些细胞是由结构化环境中的能量流驱动的。我们将探索这个基本的组织原理：跨越障碍的能量流驱动有机分子的合成——生长——以及基因遗传所需的构建块。我们的具体目标是：(i)了解增长的动力；（ii）利用生物学作为原代谢的指南；（iii）解决原始细胞中遗传密码的起源。我们之前已经详细说明了可能的机制。在这项资助中，我们将严格模拟从严格无机但结构化的环境（如在热液系统中跨越无机屏障的地质持续质子梯度）到具有基本遗传形式的简单原始细胞的形成，以及最终在原始细胞中出现真正的遗传遗传的步骤。我们将通过实验测试这种计算模型的预测，使用微流控反应器和基于细胞化学的可能的益生元条件筛选的组合。我们将把实验结果反馈到模型中，以完善我们的概念，并最终提供对生命能量规律的连贯、综合的理解。我们广泛的试点数据为这里提出的工作提供了强有力的证据。我们相信这些规则将有助于阐明在一个地质活跃但贫瘠的星球上驱动生命存在的力量。我们主要感兴趣的是了解控制生命出现的规则，但我们的工作也对寻找宇宙中其他地方的生命有意义，指导未来的太空探索。在国内，这项工作对理解我们自身的代谢结构具有重要意义，可能阐明终身健康和疾病中正常和改变的代谢通量模式。最后，利用一种仿生的能量流形式将二氧化碳固定为有机分子，可以促进碳捕获以生产合成汽油，从而为能源安全提供净零排放的解决方案。