Protocell-assisted primitive genome replication

所有已知的生物都将它们的遗传信息编码在核酸中。遗传信息的传播(例如遗传)依赖于核酸复制。现代细胞使用一系列高度进化的机器来产生遗传物质，而原始细胞(原细胞)将依赖于更简单的化学驱动的过程。至少，早期的生命形式需要一个基因组(如核糖核酸，也被称为RNA)和一个原始细胞壁(在细胞内外之间建立一道屏障)。这项研究将面临一个长达50年的问题，这个问题扼杀了自下而上合成能够支持达尔文进化的系统的方法。我们将创新性地探索原细胞膜如何积极参与RNA基因组复制。这一新的和未被探索的膜特征将展示原细胞壁驱动基因组复制的新的和完整的功能。我们的目标是首先开发与原细胞壁具有高亲和力的合适的核酸-脂结合物，因为核酸本身通常不会被吸引到原细胞壁。我们将研究锚定结合物的原始核酸(生物)化学，并对所产生的原始细胞进行生物物理表征。最后，根据以上实验的结果，我们将反复优化核酸-脂联物的设计和膜成分，实现全周期的复制。这项研究的发现将阐明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。这项研究的结果将促进我们对原细胞壁的基本理解，而不是它在生命起源中众所周知的作用(例如，主要起到细胞内部与环境之间的物理屏障的作用)。从这个高风险和高回报的项目中获得的创新将使加拿大受益，因为它将提供有关生命起源这一主题的尖端和世界知名的科学成果。

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.