Protocell-assisted primitive genome replication

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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.