Molecular Origins of Life, Munich 2023




The Molecular Origins of Life, Munich conference addresses one of the most fundamental questions of science: How could life originate? With 26 talks by renown scientists accompanied by Q&A, meet the speaker and poster sessions, this international conference brings together scientists from a wide range of disciplines, namely: astrophysics, biochemistry, biophysics, chemistry, geosciences and theoretical physics, not only to exchange knowledge and expertise but also to trigger collaborations and create more connections within the 'Origins of Life' society.

The Molecular Origins of Life, Munich 2023 is organized and sponsored by DFG funded Collaborative Research Center 235 Emergence of Life and the attendance to the event is free of charge.

Should you like to receive access to the Virtual Poster Session the registration deadline is Thursday, June 15th!

To listen to the talks, the registration is possible until the conference start!

    • 10:50 AM 11:00 AM
      Welcome Note & Info 10m
    • 11:00 AM 11:50 AM
      Session I: Talks
      Conveners: Miho Yanagisawa (U Tokyo, JP), Tomoaki Matsuura (ELSI, Tokyo Inst Tech, JP)
      • 11:00 AM
        Constructing artificial cells that can evolve based on the function of membrane proteins 25m

        One of the important features of living systems is their evolvability and their ability to interact with the extracellular environment. Once such a system can be constructed, we will be able to observe the evolutionary processes in the laboratory at a molecular level. However, constructing such molecular systems is a challenge because of the difficulties in working with membrane proteins, very hydrophobic molecules that are prone to aggregate. We encapsulated a reconstituted in vitro transcription-translation system inside a cell-sized phospholipid vesicle together with the DNA encoding membrane protein of interest. In this way, a hydrophobic environment was supplied to the membrane proteins to fold and function to interact with the extravesicular environment. To implement the evolvability to the system, the copy number of DNA inside each vesicle was adjusted to become nearly one. By assessing the functions of membrane proteins with a fluorescence-activated cell sorter, the artificial cell could evolve based on the function of the membrane proteins. I will also describe our recent approaches to adding more complexity to our artificial cellular system.

        Speaker: Tomoaki Matsuura (ELSI, Tokyo Inst Tech, JP)
      • 11:25 AM
        From cell-size confinement effects on polymer solutions to the physical significance of cell size 25m

        The size of cells ranges from 0.1 to 100 μm, regardless of the type of living cells. We have approached the physicochemical meaning using μm-sized polymer droplets covered with a lipid layer as artificial cells. From the molecular analysis inside the artificial cells, we have found that the properties and phase transitions of polymers confined to the artificial cell often differ from those in bulk systems. The effect that causes this difference is referred to as the cell size space effect (CSE) [1, 2]. In this talk, I will present two examples of CSEs. In the case of molecular diffusion in one-component polymer solutions, polymer diffusion is slower than diffusion within larger cells when the artificial cell size is smaller than ~100 μm. In the case of two-component polymer solutions, phase separation is induced within the cell size space even under conditions that maintain a uniform phase in bulk. These CSE-induced alternations are somewhat unexpected given that the spatial size scale of cells is more than two orders of magnitude larger than that of molecules. We have qualitatively explained these phenomena by considering the length-dependent membrane wettability of polymers. Based on these results, we will discuss the role of cell size space in regulating molecular behavior.

        1. Watanabe, et al., ACS Material. Lett., 2022, 4:17422.
        2. Yanagisawa, et al., Langmuir, 2022, 38:11811

        Speaker: Miho Yanagisawa (U Tokyo, JP)
    • 11:50 AM 12:00 PM
      Session I: Q&A
    • 12:00 PM 12:50 PM
      Session II: Talks
      Conveners: Hannes Mutschler (TU Dortmund, DE), Philippe Nghe (ESPCI-PSL, France)
      • 12:00 PM
        Towards a protein-free biology 25m

        Polynucleic acids such as RNA are thought to have played a central role in the origin of life on Earth. Similar to modern biology, replication and rearrangement of sequence information were most likely essential for the evolutionary development of simple life forms. However, neither the catalysts, cofactors, nor environmental conditions that were necessary for these reactions are known. Using ribozyme-based model systems, we are collaborating with other researchers to investigate the suitability of plausible non-equilibrium microenvironments and cofactors such as short peptides to promote RNA replication, early gene expression, horizontal gene transfer and phenotype-genotype coupling in model RNA protocells.

        Speaker: Hannes Mutschler (TU Dortmund, DE)
      • 12:25 PM
        Assessing the probability of autocatalytic RNAs using generative models and high-throughput screening 25m

        The RNA world hypothesis proposes that RNAs carry catalytic activity necessary for primordial evolution. A first necessary condition for evolution is reproduction. Whether self-reproduction is rare or common in the space of RNA sequences is central to assess the plausibility of this scenario. To date, two ribozymes have been shown to autocatalytically sustain their self-reproduction in the laboratory, starting from RNA oligomers: the Azoarcus ribozyme derived from the group I intron family (Hayden and Lehman 2006) and a fragmented ligase (Lincoln and Joyce 2009). In this project, we assess the probability of self-reproducing RNAs in sequence space by using as a starting point the Azoarcus ribozyme that can autocatalytically self-reproduce.

        We show that combining in silico and in vitro screening allows for the discovery of a large number of artificial self-reproducing ribozymes. For this, the strategy consists of: i) Identifying natural self-reproducing GIIs; ii) Applying physics-based and machine learning methods to generate artificial candidates for self-reproduction; iii) Testing designed sequences for self-reproduction using high-throughput sequencing; v) characterizing the representative self-reproducers.
        We find that generative models that combine statistical signatures from pair correlations and secondary structure prediction are efficient at producing functional ribozymes more than 60 nucleotides away from the original sequence, whereas random mutations destroy activity after only a few. These methods interpolate the natural diversity found in group I introns, from which self-reproducers can be successfully re-engineered. This overall shows that self-reproduction is not an exceptional property of a few laboratory-made RNAs, but is relatively widespread in the sequence space.

        Speaker: Philippe Nghe (ESPCI-PSL, France)
    • 12:50 PM 1:00 PM
      Session II: Q&A
    • 1:00 PM 1:45 PM
      Meet the Speakers of Sessions I & II 45m
    • 1:45 PM 3:00 PM
      Poster Session I
    • 3:00 PM 3:50 PM
      Session III: Talks
      Conveners: Evan Spruijt (Radboud U, NL), Filipa L. Sousa (U Vienna, AT)
      • 3:00 PM
        Retracing the modular evolution of Life by exploring extant genomes 25m

        The concept of a modular structure in life refers to the organization of living organisms into distinct functional units, or modules, which work together to perform specific tasks or functions [1]. These modules can be considered as discrete components that can be rearranged or combined in various ways to adapt to different environmental conditions or evolutionary pressures. In the context of bioenergetics evolution, this can be seen by the non-homologous replacement of complexes in a pathway or by the reshuffling of a set of “block pieces” to create new functions. At the core of such complexes are metal and organic cofactors or coenzymes that often participate in the redox reactions promoting the chemiosmosis coupling and oxidative phosphorylation [2].

        The technologic progress of the last years is allowing to expand our knowledge regarding the living world not only by unraveling a myriad of previously unknown lineages, but also regarding the ways microbes conserve energy from the environment. At the origin of life, not all of the currently known bioenergetic solutions would have been present. On the other hand, it is becoming increasingly clear that the evolution of lineages (systematics) is decoupled from the evolution of the ways they harness energy from the environment for ATP production. The later is instead, tightly connected with Earth history.

        The combination of large-scale comparative and phylogenetic analyses to study the evolution of the major modular players or “block pieces” frequently found in energy conservation solutions has been proven to be a powerful tool for unraveling the intricate relationships between energy conservation, evolutionary history, and functional diversity in the context of bioenergetics. Here, using a phylogenetic approach, we discuss our results regarding the evolution of the Dsr-pathway and it’s blocks, considering also Earth history and the potential evolution of earlier organisms [3,4].

        1. Hartwell, L., et al. From molecular to modular cell biology. Nature 402 (Suppl 6761), (1999).
        2. Mitchell, P. Chemiosmotic coupling in energy transduction: A logical development of biochemical knowledge". Journal of Bioenergetics. 3 (1), (1972).
        3. Chernyl, N. et al. Dissimilatory sulfate reduction in the archaeon ‘Candidatus Vulcanisaeta moutnovskia’ sheds light on the evolution of sulfur metabolism. Nat. Microbiol 5(11), (2020)
        4. Neukirchen, S., et al. (in revision)

        Speaker: Filipa L. Sousa (U Vienna, AT)
      • 3:25 PM
        When coacervates meet membranes 25m

        Coacervates, are condensed liquid-like droplets that are formed by liquid-liquid phase separation of peptides, nucleic acids and small molecules. They have been proposed as promising protocell candidates, because of their spontaneous formation and membrane-free nature, which allows for the uptake and concentration of a wide range of nutrients and building blocks required for life. However, the absence of a membrane also renders them unstable and prone to fusion, wetting and disintegration. Recent findings show that coacervate droplets can interact with membranes in different and unexpected ways. Here, we discuss how the interaction between coacervates and membrane can be tailored and utilized to create hybrid protocells, reshape membranes, deliver vital building blocks across membranes, and achieve intracellular organization in protocells.

        Speaker: Evan Spruijt (Radboud U, NL)
    • 3:50 PM 4:00 PM
      Session III: Q&A
    • 4:00 PM 4:50 PM
      Session IV: Talks
      Conveners: Matthew W. Powner (UCL, UK), Zoe R. Todd (U Washington, USA)
      • 4:00 PM
        On the unified roots of biological peptides and their spontaneous differentiation 25m

        The chemical unity of life’s universal metabolites provides compelling evidence that a simple set of predisposed reactions predicated the appearance of life on Earth. However, the nature of the chemistry that preceded life remains an open question. Prebiotic systems chemistry is now providing unprecedented scope to explore the origins of life and an exciting new perspective on a 4-billion-year-old problem. At the heart of this new systems approach is an understanding that individual classes of metabolites cannot be considered in isolation if the chemical origin of life on Earth is to be successfully elucidated.

        In this talk several recent advances that suggest proteinogenic peptides and life’s universal co-factors are both chemically predisposed to form will be presented. Two different classes of universal metabolite will be shown to be facilely synthesized in water, through non-enzymatic chemistry. It will also be demonstrated that the pathways to these structures spontaneously and selectively differentiate.

        Speaker: Matthew W. Powner (UCL, UK)
      • 4:25 PM
        Growth of prebiotically plausible fatty acid vesicles proceeds in the presence of prebiotic amino acids, dipeptides, sugars, and nucleic acid components 25m

        Fatty acid vesicles may have played a role in the origin of life as a major structural component of protocells, with the potential for encapsulation of genetic materials. Vesicles that grew and divided more rapidly than other vesicles could have had a selective advantage. Fatty acid vesicles grow by incorporating additional fatty acids from micelles, and certain prebiotic molecules (e.g., sugars, nucleobases, and amino acids) can bind to fatty acid vesicles and stabilize them. Here, we investigated whether the presence of a variety of biomolecules affects the overall growth of vesicles composed of decanoic acid, a prebiotically plausible fatty acid, upon micelle addition. We tested 31 molecules, including 15 dipeptides, 7 amino acids, 6 nucleobases or nucleosides, and 3 sugars. We find that the initial radius and final radius of vesicles are largely unaffected by the presence of the additional compounds. However, three dipeptides enhanced the initial rates of growth compared to control vesicles with no small molecules added; another three dipeptides decreased the initial rates of growth. We conclude that vesicles can indeed grow in the presence of a wide range of molecules likely to have been involved in the origin of life. These results imply that vesicles would have been able to grow in complex and heterogeneous chemical environments. We find that the molecules that enhance the initial growth rate tend to have hydrophobic groups (e.g., leucine), which may interact with the lipid membrane to affect growth rate; furthermore, the molecules that cause the largest decrease in initial growth rate are dipeptides containing a serine residue, which contains a hydroxyl group that could potentially hydrogen-bond with the fatty acid carboxylate groups.

        Speaker: Zoe R. Todd (U Washington, USA)
    • 4:50 PM 5:00 PM
      Session IV: Q&A
    • 5:00 PM 5:45 PM
      Meet the Speakers of Sessions III & IV 45m
    • 5:45 PM 7:00 PM
      Poster Session II
    • 11:00 AM 12:15 PM
      Session V: Talks
      Conveners: Norikazu Ichihashi (U Tokyo, JP), T-Y. Dora Tang (MPI-CBG, DE), Tim Lichtenberg (U Groningen, NL)
      • 11:00 AM
        Development of diversity and ecological complexity in the experimental evolution of an RNA-protein replicator 25m

        One of the most popular scenarios for the origin of life is as follows. First, organic molecules, such as amino acids and nucleotides, were prebiotically synthesized on the early Earth, forming polymers, peptides, RNA, and so on. Some of the polymers acquired the ability to self-replicate and began Darwinian evolution to become more complex and closer to the extant living organisms. Our research interest is in the later part of this scenario, the complexification process of self-replicating molecules through Darwinian evolution. How do self-replicating molecules evolve to become more complex, closer to existing living organisms? Is the ability of Darwinian evolution sufficient for the emergence of life, or are other conditions required? To answer these questions experimentally, we have constructed a translation-coupled RNA replication system from a genomic RNA encoding an RNA replication enzyme and a reconstituted translation system of E. coli as an experimental model. Through a long-term serial dilution process of the system, we found that a parasitic RNA species lacking the RNA replication enzyme gene emerged and coevolved with the genomic “host” RNA species. Coevolution accelerated the evolution and induced diversification of both host and parasitic RNAs into at least five lineages. Furthermore, the diversified RNAs were initially competitive, but formed a complex, interdependent replication network. These results support that parasitic replicators might play an important role in the diversification and ecological complexification of prebiotic self-replicators.

        Speaker: Norikazu Ichihashi (U Tokyo, JP)
      • 11:25 AM
        Peptide-nucleic acid coacervation as a route to primitive compartmentalisation 25m

        In the 1920’s Oparin hypothesized that membrane free compartments formed by coacervation would have provided a viable route to compartmentalize prebiotic reactions as a precursor to the modern cell. Studies which support this hypothesis are limited in that the precise chemical composition and conditions on prebiotic earth remain a mystery. Despite this, using bottom-up approaches allows us to generate physically relevant protocell models in the lab. This provides a means to unravel the effect of compartmentalization by coacervation can have provided a selection pressure for facilitating the transition from a chemical world to a biological world.

        Here, I will present strategies for the design and synthesis of protocell models based on liquid-liquid phase separation of oppositely charged components (coacervates) and describe how these compartments could be viable protocells models by bringing together peptides and RNA.

        Speaker: T-Y. Dora Tang (MPI-CBG, DE)
      • 11:50 AM
        Molten Exoplanets as a Window into the Earliest Earth 25m

        Due to the absence of a reliable rock record from the Hadean eon, our understanding of the environment that gave rise to life on our own planet is clouded. Current and upcoming exoplanet surveys, however, significantly widen our view of the distribution and variability of rocky planets and their chemical inventories, giving opportunity to test scenarios of early planetary evolution and atmospheric formation. I will describe how rocky exoplanets in a partially or fully molten state open a novel window into on the earliest, high-temperature evolutionary regime of rocky worlds. Increasing reconnaissance of high-temperature super-Earths will enable us to infer the early climatic and geodynamic evolution of temperate rocky worlds, providing crucial information on the environmental context of the origins of life on Earth and are the next key step toward the characterisation of prebiotic and potentially habitable exoplanets.

        Speaker: Tim Lichtenberg (U Groningen, NL)
    • 12:15 PM 12:30 PM
      Session V: Q&A
    • 12:30 PM 1:20 PM
      Session VI: Talks
      Conveners: Golo Storch (TU Munich, DE), Sudha Rajamani (IISER Pune, IN)
      • 12:30 PM
        Molecular Flavins: Catalytic Activity outside Enzymes 25m

        Modern flavoenzymes are among nature’s most versatile catalysts and mediate reactions ranging from oxidations, oxygenations, ring contractions, to reductions [1]. This diversity stems from the occurrence of different catalytically active states of the cofactor’s isoalloxazine heterocycle, which is the reactive center of both flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). However, the astonishingly broad reactivity spectrum of flavoenzymes stands in contrast to the
        currently limited synthetic use of molecular flavins [2]. Their plausible prebiotic origin also raises the question whether flavins played an important role in mediating crucial transformations at the molecular origins of life [3]. In order to bridge this gap, we focus on the synthesis and application of molecular flavin catalysts in organic transformations.

        Our first example uses C6-ester-modified flavins [FlCat]* for the modification of dehydroamino acids. We showed that covalent flavin adducts are involved and that β-alkoxamines are obtained with the persistent radical TEMPO under catalytic conditions [4]. Inspired by the activity of flavin hydroperoxides [FlCat-C4a-OOH] in halogenases, we prepared molecular flavins for O2-reduction and subsequent bromination with inorganic halide salt [5]. Modified catalysts are operative under mild conditions, while the isolated cofactor (‒)-riboflavin is unproductive. We have also found a strategy to use visible-light excitation of flavins for one-electron reduction of barbiturate substrates, replacing the typically used super-stoichiometric metal reductants with the essential oil γ-terpinene [6].

        1. (a) M. Toplak, R. Teufel, Biochemistry 2022, 61, 47–56; (b) C. T. Walsh, T. A. Wencewicz, Nat. Prod. Rep. 2013, 30, 175‒200.
        2. A. Rehpenn, A. Walter, G. Storch, Synthesis 2021, 53, 2583‒2593.
        3. A. Kirschning, Angew. Chem. Int. Ed. 2021, 60, 6242‒6269.
        4. A. Rehpenn, A. Walter, G. Storch, Chem. Sci. 2022, 13, 14151‒14156.
        5. A. Walter, G. Storch, Angew. Chem. Int. Ed. 2020, 59, 22505‒22509.
        6. R. Foja, A. Walter, C. Jandl, E. Thyrhaug, J. Hauer, G. Storch, J. Am. Chem. Soc. 2022, 144, 4721‒4726.

        Speaker: Golo Storch (TU Munich, DE)
      • 12:55 PM
        Tales of select protocellular systems 25m

        The enduring mystery of life's origins involves an important step of discerning the emergence of the first cells on the early Earth. Understanding this involves studying the fundamental components of a putative protocell and how they interact with each other, potentially resulting in the emergence of the first protocellular systems. In this backdrop, we at the COoL lab have been focussing on characterizing robust protocellular systems, in addition to also describing prebiotically minimally described amphiphilic systems, to gain a better understanding of the putative prebiotic amphiphilic landscape. Pertinently, these studies have involved studying the physicochemical properties of amphiphilic systems, to better understand their responses to prebiotically pertinent selection pressures. In the latter context, I will share our work on how we stumbled upon a protoamphiphilic moiety, whose spontaneous emergence in a prebiotically pertinent reaction also underscored the importance of exploring co-evolutionary processes (e.g. membrane assembly and peptide synthesis). All the understanding from our recent "amphiphilic sojourns" has led to renewed appreciation of how heterogeneity intrinsic to the prebiotic soup would have shaped the emergence and evolution of protocellular systems.

        Speaker: Sudha Rajamani (IISER Pune, IN)
    • 1:20 PM 1:30 PM
      Session VI: Q&A
    • 1:30 PM 2:15 PM
      Meet the Speakers of Sessions V & VI 45m
    • 2:15 PM 3:30 PM
      Poster Session III
    • 3:30 PM 4:20 PM
      Session VII: Talks
      Conveners: Claudia Höbartner (U Würzburg, DE), Meng Su (MRC LMB, UK)
      • 3:30 PM
        The Origin of Genetic Code 25m

        In extant life, DNA stores genetic information while proteins carry out biochemical functions. The central dogma explains how nucleotides are translated into amino acids through tRNA. tRNA is essential in translation as it connects the codon and the cognate amino acids. However, we are still uncertain about the basis on which codon:amino acid assignments were initially made. Two hypotheses have been in debate for 60 years: stereochemical theory and frozen accident theory. Limited experimental work bearing on this question has left answers mainly in the realm of conjecture.

        We reported an enzyme-free RNA aminoacylation reaction. In a tRNA acceptor stem-overhang mimic, overhang sequences do not influence the chemoselectivity of aminoacylation significantly, but the terminal three base pairs of the stem do. Computational simulations have also demonstrated that the amino acids interact with the three base pairs, leading to chemoselectivity and stereoselectivity. The findings support early suggestions of a second genetic code in the tRNA acceptor stem.

        The terminal three base pairs that selectively transfer a specific amino acid share no similarity to the codon of the same amino acid, which prompted us to wonder if the earliest assignment was determined by the difference in binding strength between the mRNA triplet codon and the tRNA anticodon loop. The binding kinetics of 64 triplets to anticodon loops were measured using isothermal titration calorimetry (ITC) and biolayer interferometry (BLI). Cytosine-ending codons from four-fold degenerate boxes bind tighter than codons from two-fold degenerate boxes. BLI assay also shows that two anticodon loops can bind to a single-stranded RNA if they are in the four-fold degenerate boxes. The dataset suggests that prebiotic amino acids are first assigned to the anticodons which bind codons tighter.

        Combining the data from the tRNA acceptor stem and anticodon loop, the two hypotheses mentioned above can be reconciled. The amino acids interact with the acceptor stem to selectively aminoacylate the CCA end, while the tRNA acceptor stem domain engages with the anticodon domain randomly. Therefore, a better explanation for the Origin of Genetic Code is likely a combination of the two hypotheses.

        Speaker: Meng Su (MRC LMB, UK)
      • 3:55 PM
        RNA catalysis beyond phosphodiester chemistry: RNA methylation catalyzed by a methyltransferase ribozyme 25m

        Modified nucleotides expand the structural and functional diversity of RNA, and many of them are highly conserved throughout evolution. Nucleobase methylation is the smallest modification installed by specialized enzymes that use nucleotide cofactors such as S-adenosylmethionine, which may be considered as “evolutionary leftovers” from an RNA world. We speculate that methylated nucleotides could have influenced the evolutionary path of catalytic RNA. Ribozymes may have installed modifications to enhance catalysis or mediate their removal to facilitate replication and storage of genetic information. Using in vitro evolution, we found a modern analogue of such a ribozyme that catalyses the site-specific methyl transfer reaction from a cofactor to RNA. We studied the structure of the methyltransferase ribozyme together with the methylated RNA and report insights into cofactor binding site and catalytic mechanism.

        Speaker: Claudia Höbartner (U Würzburg, DE)
    • 4:20 PM 4:30 PM
      Session VII: Q&A
    • 4:30 PM 5:20 PM
      Session VIII: Talks
      Conveners: Jack W. Szostak (University of Chicago), Nita Sahai (U Akron, USA)
      • 4:30 PM
        From RNA Copying Chemistry to RNA Replication 25m

        I will discuss recent advances in the chemistry of nonenzymatic RNA copying, including potentially prebiotic pathways for activation chemistry that are compatible with template-directed primer extension. I will also discuss the Virtual Circular Genome model for RNA replication within protocells, and recent experimental tests of this model.

        Speaker: Jack W. Szostak (University of Chicago)
      • 4:55 PM
        MuSeCOL: Mineral-Catalyzed Mutualism and Selection from a Complicated Broth in the Origins of Life 25m

        The appearance of life at ~ 4 Ga was a result of complex geochemical events involving the interaction of primitive atmosphere, water, dissolved ions, and minerals leading to the abiotic (nonenzymatic) synthesis of biomolecule monomers or their precursors, that were selected from a complicated prebiotic molecular broth and polymerized into oligomers, and ultimately self-assembled to form the earliest life-like entities (protocells). The focus of our research is to discover the potential role of minerals and dissolved metal ions in these processes and in the development of transmembrane ion gradients that represent chemiosmotic potentials for driving protometabolic reactions. A long-standing question in this field is whether RNA, enzymes (proteins) or lipid membranes evolved first because in extant biology, each requires the other. We have hypothesized the MuSeCol model in which minerals and dissolved ions present in the Hadean geochemical environment catalyzed the synthesis of these biomolecules by mutual (Mu) coevolution with specific isomer selection (Se) from a complicated (C) prebiotic broth as well as promoted transmembrane pH gradients leading to the Origins of Life (OL). I will share results from some of our studies supporting this hypothesis.

        Speaker: Nita Sahai (U Akron, USA)
    • 5:20 PM 5:30 PM
      Session VIII: Q&A
    • 5:30 PM 6:15 PM
      Meet the Speakers of Sessions VII & VIII 45m
    • 11:00 AM 11:50 AM
      Session IX: Talks
      Conveners: Hikaru Yabuta (Hiroshima U, JP), Paul B. Rimmer (U Cambridge, UK)
      • 11:00 AM
        Organic Matter in the Samples of Asteroid Ryugu 25m

        JAXA’s Hayabusa2 mission explored the carbonaceous asteroid Ryugu and collected its sands and pebbles. On December 6, 2020, the asteroid sample was returned to the Earth. After the curatorial work at JAXA, the initial sample analysis has conducted from June 2021 to May 2022. The Initial Analysis IOM (Insoluble Organic Matter) team unveiled the chemical, isotopic, and morphological compositions of macromolecular organic solids from the Ryugu samples by coordinating spectromicroscopies, electron microscopy, and isotopic microscopy (Yabuta et al. 2023). The Initial Analysis SOM (Soluble Organic Matter) team revealed the distributions of soluble organic molecules from the Ryugu samples using high-sensitive and high-resolution mass spectrometry techniques (Naraoka et al. 2023).

        Our study has proved the direct link between organic matter in the C-type asteroid Ryugu and that in primitive carbonaceous chondrites. The chemical, isotopic, and morphological diversities of Ryugu's organic matter record various degrees of parent body aqueous alteration and preserve the materials derived from nebula or molecular cloud. The organic matter in C-type asteroids could have contributed to the formation of habitable planetary environments.

        Speaker: Hikaru Yabuta (Hiroshima U, JP)
      • 11:25 AM
        Krebs cycle intermediates as tracers of prebiotic chemistry 25m

        In certain local aqueous environments, ultraviolet (UV) light can transform single-carbon molecules into precursors of RNA, DNA, proteins and phospholipid vesicles. This happens when one of the single-carbon molecules is hydrogen cyanide. Carbonate was likely more ubiquitous than cyanide. If carbonate is present instead of cyanide, a series of molecules are formed, mostly formate, and also oxalate and a group of Krebs cycle intermediates. Constraining rate constants for the formation and destruction of these molecules in aqueous surface environments will provide a way to predict chemical evolution in aqueous surface environments of rocky planets over geological time. I will present experimental constraints for rate constants for the production of formate, oxalate, citrate, malate and succinate, as a function of UV intensity and pH. I then apply these rate constants to an aqueous chemical kinetics model to predict the change in relative concentrations of species as a function of time, pH, temperature, and UV intensity. I will conclude with a brief discussion about predictions for the surface chemistry on Mars, and how this chemical network fits into the larger context of prebiotic chemistry on rocky planets

        Speaker: Paul B. Rimmer (U Cambridge, UK)
    • 11:50 AM 12:00 PM
      Session IX: Q&A
    • 12:00 PM 12:50 PM
      Session X: Talks
      Conveners: James Attwater (UCL, UK), Philippe Schmitt-Kopplin (Helmholtz & TU Munich, DE)
      • 12:00 PM
        The molecular atlas of soluble organic matter of meteorites and of Ryugu C-type asteroid parent body 25m

        We present here a review of the state of the art in non-targeted high resolution analysis of the soluble organic fraction of various meteorites; these include carbonaceous chondrites as well as achondrites and ordinary chondrites in the light of the analysis of the sample return missions HAYABUSA2 and OSIRIS ReX.

        Understanding the origin and evolution of organic matter, is linked to observation derived astrochemistry (telescopic observations) and the laboratory wet chemical analysis of return objects and meteorites. The molecular composition and diversity of non-terrestrial organic matter in carbonaceous chondrites was studied by means of both, targeted and non-targeted chemical analytical approaches, leading to new molecular insights. Targeted chemical analyses are hypothesis-driven and are largely focused on molecules of biological/prebiotic interest. In a non-targeted approach, all analytes are globally profiled within the analytical possibilities without biased or constrained hypothesis in order to gain comprehensive information. We review in this presentation the state of the art in using non-targeted high resolution organic spectroscopy.

        Ultrahigh-resolving analytics, like high field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and nuclear magnetic resonance spectroscopy (NMR), represent a powerful tool to allow insights into the holistic complex compositional space to tens of thousands of different molecular compositions and functional groups and likely millions of diverse structures. This could be observed in solvent extracts of pristine carbonaceous meteorites, and suggests that interstellar chemistry is extremely active and rich. Since then we studied the chemical composition of thousands of individual components out of complex organic mixtures, as accessed in the solvent-accessible organic fraction, extracted under mild conditions, from diversely-classified and heated meteorites.

        We described that heteroatomic organic molecules play an important role in the description of non-terrestrial chemical evolution. The thermally and shock-stressed Chelyabinsk (LL5) showed high number of nitrogen counts within CHNO molecular formulas, especially in the melt region. This match of the organic molecular profile with the petrologic character could be also observed for Novato (L6), Braunschweig (L6) and the latest German fall Stubenberg (LL6). Additionally, the extremely thermally altered Sutter’s mill (C-type) reflects a loss in the organic diversity, but an increase in the polysulphur domain, as compared to other CM2-analyzed falls. The increase of polynitrogen and polysulphur compounds could be simulated in laboratory experiments by heating Murchison (CM2). Recently we reported the discovery of a previously unrecognized chemical class, dihydroxymagnesium carboxylates, [(HO)2MgO2CR]−, gained from non-terrestrial meteoritic analyses. These thermostable compounds might have contributed to the stabilization of organic molecules on a geological time scale, which emphasizes their potential astrobiological relevance. The resulted extreme richness in chemical diversity analyzed in meteorites offers information on the meteoritic parent body history and help in expanding our knowledge or astrochemistry towards higher molecular masses and complex molecular structures.

        The sample from the near-Earth carbonaceous asteroid (162173) Ryugu collected by the Hayabusa2 spacecraft did not see any terrestrial alteration and could be analyzed in the context of carbonaceous meteorites SOM. The analysis of soluble molecules of Ryugu samples collected by the Hayabusa2 spacecraft shine light on an extremely high molecular diversity on the C-type asteroid. Sequential solvent extracts of increasing polarity in hexane, dichloromethane, methanol and water of Ryugu samples were analyzed using ultrahigh resolution mass spectrometry with complementary ionization methods and structural information confirmed by nuclear magnetic resonance spectroscopy and interpreted in the light of the knowledge rised on meteoritic organic matter.

        Speaker: Philippe Schmitt-Kopplin (Helmholtz & TU Munich, DE)
      • 12:25 PM
        Open-ended amplification of RNA by a ribozyme 25m

        Early biology is thought to have propagated its genetic information through strands of RNA. To recapitulate this process in the laboratory, ribozymes have been developed that polymerise short RNA building blocks on a template strand. This synthesis activity has the potential to support a biological behaviour – RNA replication – if the double-stranded RNA product can be separated into fresh template strands for use in further cycles of synthesis. However, such strand separation is both kinetically and thermodynamically unfavourable, as RNA duplexes are difficult to separate and quick to reanneal.

        I will present an unexpected capacity for trinucleotide ‘triplet’ RNA building blocks to solve this strand separation problem. They allow iterative cycles of strand synthesis and strand separation to drive ribozyme-catalysed exponential amplification of RNA. I will then discuss what happens in open-ended amplification reactions supported by this all-RNA replication system.

        Speaker: James Attwater (UCL, UK)
    • 12:50 PM 1:00 PM
      Session X: Q&A
    • 1:00 PM 1:45 PM
      Meet the Speakers of Sessions IX & X 45m
    • 1:45 PM 3:00 PM
      Poster Session IV
    • 3:00 PM 3:50 PM
      Session XI: Talks
      Conveners: Karen Alim (TU Munich, DE), Thomas E. Ouldridge (Imperial College London, UK)
      • 3:00 PM
        Alkaline Vents Recreated in Two Dimensions to Study pH Gradients, Precipitation Morphology and Molecule Accumulation 25m

        Alkaline vents (AV) are hypothesized to have been a setting for the emergence of life, by creating strong gradients across inorganic membranes within chimney structures. In the past, 3-dimensional chimney structures were formed under laboratory conditions, however, no in situ visualisation or testing of the gradients was possible.

        We develop a quasi-2-dimensional microfluidic model of alkaline vents that allows spatio-temporal visualisation of mineral precipitation in low volume experiments. Upon injection of an alkaline fluid into an acidic, iron-rich solution, we observe a diverse set of precipitation morphologies, mainly controlled by flow-rate and ion-concentration. Using microscope imaging and pH dependent dyes, we show that finger-like precipitates can facilitate formation and maintenance of microscale pH gradients and accumulation of dispersed particles in confined geometries.

        Our findings establish a model to investigate the potential of gradients across a semi-permeable boundary for early compartmentalisation, accumulation and chemical reactions at the origins of life.

        Speaker: Karen Alim (TU Munich, DE)
      • 3:25 PM
        Chemically-driven molecular templating 25m

        The templating of sequence-specific assembly is at the heart of biological complexity; DNA replication, RNA transcription and protein translation are all examples of this process. Extant biological systems exhibit high-fidelity templating of long polymers using purely chemical driving forces; the question of how simpler processes of this kind emerged is at the heart of the origin of life.

        Hitherto, efforts to build systems that perform molecular templating without either highly-evolved enzymes or a non-chemical supply of energy have met with limited success. A key challenge is in overcoming product inhibition - the tendency of products to adhere to their templates, an effect that gets exponentially worse with copy length.

        We introduce a DNA-based reaction mechanism, handhold-mediated strand displacement (HMSD), that allows for chemically-driven, sequence-specific templating with low product inhibition. We show how HMSD-based templates are effective catalysts for dimerisation, and demonstrate both kinetic proofreading and self-replication with this system.

        Speaker: Thomas E. Ouldridge (Imperial College London, UK)
    • 3:50 PM 4:00 PM
      Session XI: Q&A
    • 4:00 PM 5:15 PM
      Session XII: Talks
      Conveners: David Catling (U Washington, USA), Emmanuelle J. Javaux (U Liège, BE), Zachary Cohen (U Washington, USA)
      • 4:00 PM
        Expected composition of the atmosphere and surface waters on the early Earth that favored the origin of life 25m

        How life originated is how geochemistry became biochemistry. Consequently, knowing the environmental geochemistry prior to the origin of life is crucial. Here, I discuss the expected chemical composition of the early atmosphere and surface waters. In the Hadean, calculations show that chemically reducing atmospheres are inevitable consequences of large impacts and would have lasted millions of years, producing copious nitriles that rained out to the surface, serving as feedstocks for nucleobase synthesis. Also on the early Earth, evaporative soda lakes (i.e., rich in sodium carbonate) are likely inevitable because such lakes arise when water pools in closed basins in basaltic rocks and the aquatic chemistry evolves. The chemistry of such lakes encourages the sequestration and concentration of key species needed for prebiotic synthesis, such as cyanide and phosphate. Such lakes can also promote polymerization of prebiotic molecules during the dry phase of wet-dry cycles. Indeed, one modern, evaporative soda lake, Last Chance Lake in Canada, can be considered a geochemical origin-of-life analog. This closed-basin lake sits on top of flood basalts, has suppressed nitrogen fixation (which inhibits the usual drastic biological modification of modern water chemistries), and has the highest phosphate levels in the world that reach almost ~40 mM. I postulate that similar locales on the early Earth would have favored prebiotic synthesis.

        Speaker: David Catling (U Washington, USA)
      • 4:25 PM
        Nonenzymatic RNA assembly, ribozyme activity, and encapsulation by protocell membranes within natural carbonate lakes 25m

        Carbonate lakes on the early Earth may have concentrated RNA precursors and membrane-forming fatty acids. Here, we show that natural carbonate lakes provide compatible conditions for nonenzymatic RNA assembly, ribozyme activity, and encapsulation by prebiotic membranes. Carbonate lakes contain at most ~1 mM divalent cations because carbonate salts of divalent cations are relatively insoluble. We collected water from Last Chance lake and Goodenough lake in British Columbia, Canada, which have some of the highest phosphate concentrations of any lake in the world. Because we sampled these lakes after seasonal evaporation, the lake water contained ~1 M Na+ plus ~1 mM Mg2+ at pH10. We investigated the nonenzymatic, RNA-templated extension of RNA primers by 2-aminoimidazole activated ribonucleotides. We find that the initial rate of primer extension is comparable in lake water and standard laboratory conditions (50 mM MgCl2 at pH 8). After 72 hours, we observe lower yields of extended product in lake water than in laboratory conditions, although the yield is increased by supplying a higher initial concentration of activated nucleotides. We also demonstrate that a ligase ribozyme that uses 2-aminoimidazole activated oligonucleotides as substrate is active when the natural lake water is adjusted to pH 9. Finally, we show that vesicles composed of 1:1 decanoic acid: decanol encapsulate aqueous solutes despite salt-induced flocculation in natural lake water. By identifying compatible conditions for both nonenzymatic and ribozyme-catalyzed RNA assembly, and for encapsulation by fatty acid membranes, our results suggest that natural carbonate lakes could have enabled the emergence of cellular life on the early Earth.

        Speaker: Zachary Cohen (U Washington, USA)
      • 4:50 PM
        Early traces of life 25m

        Characterizing plausible and reliable traces of microbial life is crucial to untangle the co-evolution of Earth and the biosphere. It may also inform on plausible conditions for life to emerge and evolve on a habitable planet or moon, and how to detect life beyond Earth. The origin of life (OoL) was probably possible since 4.3 billion years when Earth became habitable. Although the Earth rock record do not preserve the transition time from prebiotic molecules and vesicles to life, exploring early habitable environments on Mars and lab experiments in simulated conditions might provide some clues. Isotopic, biosedimentary, molecular and morphological traces of life suggest the early presence of prokaryotic communities for at least 3.4 billion years in diverse environments of the early Earth, implying an older LUCA, and thus an earlier OoL. Complex cells (eukaryotes) started to diversify by at least 1.8 billion years. However, these traces may in some cases also be produced and/or altered by abiotic processes or later contamination, leaving a controversy surrounding the earliest biological record. This talk will illustrate the challenges and evidence in identifying the early traces of life.

        Speaker: Emmanuelle J. Javaux (U Liège, BE)
    • 5:15 PM 5:30 PM
      Session XII: Q&A
    • 5:30 PM 6:15 PM
      Meet the Speakers of Sessions XI & XII 45m
    • 6:15 PM 6:25 PM
      Goodbye Note 10m