| Project/Area Number |
18K14354
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
ジャー トニー 東京工業大学, 地球生命研究所, 特任助教 (10800328)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Keywords | Origins of Life / Coacervates / Phase Separation / Polyesters / Prebiotic Chemistry / Protocell / Astrobiology / Chemical Evolution |
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| Outline of Annual Research Achievements |
I published many papers as corresponding author, including one high-impact paper in as first & corresponding author (Jia, et al. PNAS 116(32), 15830-5 (2019)) on segregation and function of primitive biomolecules in liquid-liquid phase separated (LLPS) polyester protocells, resulting in significant media coverage, such as in Science News. We showed that polyester microdroplet protocells are a relevant membraneless protocell amenable to function and evolution of RNA. We are now elucidating systems which allow greater compartmentalization of RNA such as incorporation of cationic groups or lipid layer scaffolds to incorporate more chemical and structural complexity. Additionally, we are expanding these studies to include droplet functionality, including RNA degradation protection ability. We have started pilot stability and materials properties assays for these protocells.
We have also performed pilot experiments for other protocell model systems. In particular, we have begun to characterize tunable and structurally complex DNA liquid crystal (LC)-coacervate droplets, which could be an amenable protocell model system (see below).
I also received many awards, including from the European Astrobiology Network Association, the French Embassy in Japan, and ELSI. I was also invited for many seminars including at the Gordon Research Conference Origins of Life and others. A large number of contributed talks at domestic and international meetings also resulted. Finally, I will be an invited speaker at the 2020 Japan Geophysical Union and Molecular Biology Society of Japan meetings.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
As one can see from the large number of publications and invited talks, we are progressing smoothly. We characterized the polyester system and demonstrated its protocellular capability. We have begun to characterize structural, chemical, and functional properties of other systems that could also be used as protocell models.
I have developed a network of collaborators in a variety of fields, both both domestically and internationally, through attendance and exposure at various international and domestic conferences (including as an organizer) as well as membership in Japanese scientific societies (Biophysical Society of Japan, Japan Society for Cell Synthesis Research, Japan Geophysical Union, Chemical Society of Japan). I also joined Blue Marble Space Institute of Science. This has allowed me to access a wealth of relevant knowledge if the need arises (and if I am not an expert in that particular topic). In particular, I joined a consortium studying all phases of LLPS, including physics, chemistry, and biology. I am able to glean significant technical and technological knowledge (while at the same time, providing my expertise in biochemistry, prebiotic chemistry, and astrobiology, to the other members).
Finally, I was promoted to Specially-Appointed Assistant Professor and now have more autonomy in implementing my research. Although I have to now additionally manage the shared Chemistry Unit laboratory, this also allows me to mobilize the proper resources for the successful research both of myself, and other colleagues (some of whom are collaborators).
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| Strategy for Future Research Activity |
We will continue to characterize and elucidate the structure and function of more complex polyester droplet systems. We have also performed pilot experiments on related membraneless systems that could effect RNA function and evolution such as droplets produced from ring-opening polymerization of macrocycles, small peptide nanofibers, DNA LC-coacervates, and combinatorial lipid assemblies. We will proceed with structural, materials, and chemical characterization of these structures, in the framework of primitive Earth geochemistry, followed by stability assays. Finally, we will probe ability of these systems to enhance ribozyme function, protect RNA from degradation, and allow polymerization and evolution of RNA.
In particular, DNA LC-coacervate droplets are a promising target, as pilot studies have shown its ability to scaffold and effect complex nucleic acid assemblies (end-to-end stacked dsDNA rods) within a DNA/peptide coacervate. This the first discovery of functional in vitro dsDNA coacervates, with implications on the evolutionary transition from single stranded nucleic acids (RNA) to duplexes (DNA). Pilot studies have shown that the LC-coacervate internal structure can significantly change according to external stimuli such as temperature, salinity, and hydration; this could be a dynamic system that could effect chemical evolution of its own compositional components, as well as encapsulated RNA. We will continue characterizing the properties of the system while simultaneously probing their ability to compartmentalize functional and evolvable RNA.
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| Causes of Carryover |
I was able to save some costs and had my publication fees waived for this year. Additionally, due to COVID19, a collaborator working on these projects could not stay as long as planned, as they had to cut their visit short by over one month. Finally, 2 meetings I had planned to attend in March 2020 were cancelled due to COVID19. Thus, I have remaining extra funding to be used for publication fees in FY2020, as well as some extra for inviting over the collaborator once again to finish the project.
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| Remarks |
Full list of media coverage available upon request.
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