Protocell-assisted primitive genome replication

原始细胞辅助原始基因组复制

• 批准号: 575558-2022
• 负责人: OFlaherty, DerekDK
• 金额: $ 1.82万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=747576
• 关键词: Protocell; assisted; primitive; genome; replication

All known organisms encode their genetic information in nucleic acids. Propagation of genetic information(e.g., inheritance) is dependent on nucleic acid replication. Whereas the modern cell uses collection of highly evolved machineries to produce its genetic material, primitive cells (protocells) would have relied on much simpler, and chemically driven, processes. At the least, early lifeforms would have required a genome (such as ribonucleic acids, also known as RNA) and a protocell wall (that creates a barrier between the inside and outside of the cell). This research will take on a 50-year problem that has stifled the bottom-up approach to synthesizing systems capable of sustaining Darwinian evolution. We will innovatively explore how the protocell membrane compartment can actively participate in the RNA genome replication. This novel and unexplored membrane feature will demonstrate a new and integral function of the protocell wall to drive genome replication. We aim to first develop suitable nucleic acid-lipid conjugates with high affinity to the protocell wall, as nucleic acids on their own are not typically attracted to protocell walls. We will investigate the primitive nucleic acid (bio)chemistry of the anchored conjugate and biophysically characterized the resulting protocells. Lastly, with findings garnered from the above experiments, we will iteratively optimize the nucleic acid-lipid conjugate design and the membrane composition, to achieve a full cycle of replication. Findings from this research will shed light on a potential protocellular symbiosis between essential components for life (genome and protocell wall). The results of this research will advance our fundamental understanding of the protocellular wall in ways other than its well-known role in the origins of life (e.g mainly acting as a physical barrier between the inside of the cell to its environment). Innovation garnered from this high risk and high reward program will benefit Canada by delivering cutting-edge and world-renounced science on the topic of the origins of life.

所有已知的生物体都在核酸中编码它们的遗传信息。遗传信息的传播（例如，遗传）依赖于核酸复制。现代细胞使用高度进化的机器集合来产生其遗传物质，而原始细胞（原始细胞）则依赖于更简单的化学驱动过程。至少，早期的生命形式需要一个基因组（如核糖核酸，也称为RNA）和一个原始细胞壁（在细胞内外之间形成屏障）。这项研究将解决一个50年来的问题，这个问题扼杀了自下而上的方法来合成能够维持达尔文进化论的系统。我们将创新性地探索原始细胞膜区室如何积极参与RNA基因组复制。这种新的和未开发的膜功能将证明一个新的和完整的功能，原细胞壁驱动基因组复制。我们的目标是首先开发对原始细胞壁具有高亲和力的合适的核酸-脂质缀合物，因为核酸本身通常不被吸引到原始细胞壁。我们将研究锚定缀合物的原始核酸（生物）化学，并对所得原始细胞进行生物表征。最后，利用从上述实验中获得的发现，我们将迭代优化核酸-脂质缀合物设计和膜组成，以实现完整的复制循环。这项研究的发现将揭示生命的基本组成部分（基因组和原细胞壁）之间潜在的原细胞共生关系。这项研究的结果将推进我们对原细胞壁的基本理解，而不是它在生命起源中的众所周知的作用（例如，主要作为细胞内部与环境之间的物理屏障）。从这一高风险和高回报计划中获得的创新将通过提供关于生命起源的尖端和世界公认的科学而使加拿大受益。