Bookmarked Nonenzymatic Template-Directed RNA Synthesis Inside Model Protocells (science.sciencemag.org)
The potential for self-replication makes RNA an attractive candidate as a primordial catalysis in the origin of life. Catalysis may have occurred in some kind of compartment, possibly a fatty acid vesicle. However, RNA catalysis generally requires high levels of magnesium, which are incompatible with fatty acid vesicle integrity. Adamala and Szostak (p. [1098][1]) screened magnesium chelators and found that several—including citrate, isocitrate, and oxalate—could maintain the membrane stability of fatty acid vesicles in the presence of Mg2+. Citrate also allowed Mg2+-dependent RNA synthesis within protocell-like vesicles, while at the same time protecting RNA from Mg2+-catalyzed degradation. Efforts to recreate a prebiotically plausible protocell, in which RNA replication occurs within a fatty acid vesicle, have been stalled by the destabilizing effect of Mg2+ on fatty acid membranes. Here we report that the presence of citrate protects fatty acid membranes from the disruptive effects of high Mg2+ ion concentrations while allowing RNA copying to proceed, while also protecting single-stranded RNA from Mg2+-catalyzed degradation. This combination of properties has allowed us to demonstrate the chemical copying of RNA templates inside fatty acid vesicles, which in turn allows for an increase in copying efficiency by bathing the vesicles in a continuously refreshed solution of activated nucleotides. [1]: /lookup/doi/10.1126/science.1241888
Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()
Bookmarked Tibor Gánti (1933- 2009): Towards the Principles of Life and Systems Chemistry (Journal of Theoretical Biology | sciencedirect.com)
Edited by Eörs Szathmáry
Volume 381, Pages 1-60 (21 September 2015)
Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()

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Bookmarked Founder of systems chemistry and foundational theoretical biologist: Tibor Gánti (1933–2009) (sciencedirect.com)
With his chemoton theory theoretical biologist and chemical engineer Tibor Gánti was one of the most outstanding intellects behind systems chemistry a…
Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()
Bookmarked Vocabulary of Definitions of Life Suggests a Definition by Edward N. Trifonov (Journal of Biomolecular Structure and Dynamics Volume 29, 2011 - Issue 2)
Analysis of the vocabulary of 123 tabulated definitions of life reveals nine groups of defining terms (definientia) of which the groups (self-)reproduction and evolution (variation) appear as the minimal set for a concise and inclusive definition: Life is self-reproduction with variations.
https://doi.org/10.1080/073911011010524992

Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()

Bookmarked Cellular Homeostasis, Epigenesis and Replication in Randomly Aggregated Macromolecular Systems by Stuart A. Kauffman (Journal of Cybernetics Volume 1, 1971 - Issue 1)
Pages 71-96 | Published online: 15 Apr 2008
https://doi.org/10.1080/01969727108545830
Proto-organisms probably were randomly aggregated nets of chemical reactions. The hypothesis that contemporary organisms are also randomly constructed molecular automata is examined by modeling the gene as a binary (on-off) device and studying the behavior of large, randomly constructed nets of these binary “genes.” The results suggest that, if each “gene” is directly affected by two or three other “genes,” then such random nets: behave with great order and stability; undergo behavior cycles whose length predicts cell replication time as a function of the number of genes per cell; possess different modes of behavior whose number per net predicts roughly the number of cell types in an organism as a function of its number of genes; and under the stimulus of noise are capable of differentiating directly from any mode of behavior to at most a few other modes of behavior. Cellular differentiation is modeled as a Markov chain among the modes of behavior of a genetic net. The possibility of a general theory of metabolic behavior is suggested. Analytic approaches to the behavior of switching nets are discussed in Appendix 1, and some implications of the results for the origin of self replicating macromolecular systems is discussed in Appendix 6.

Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()

Bookmarked Jump-starting life? Fundamental aspects of synthetic biology (Journal of Cell Biology | Rockefeller University Press | rupress.org)
What is life and how could it originate? This question lies at the core of understanding the cell as the smallest living unit. Although we are witnessing a golden era of the life sciences, we are ironically still far from giving a convincing answer to this question. In this short article, I argue why synthetic biology in conjunction with the quantitative sciences may provide us with new concepts and tools to address it.
Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()
Bookmarked The enduring value of Gánti׳s chemoton model and life criteria: Heuristic pursuit of exact theoretical biology (sciencedirect.com)
Gánti׳s chemoton model of the minimal chemical organization of living systems and life criteria for the living state and a living world are characteri…
Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()
Bookmarked Budding and Division of Giant Vesicles Linked to Phospholipid Production by Juan M. Castro, Hironori Sugiyama, Taro Toyota (Scientific Reports volume 9, Article number: 165 (2019))
The self-reproduction of supramolecular assemblies based on the synthesis and self-assembly of building blocks is a critical step towards the construction of chemical systems with autonomous, adaptive, and propagation properties. In this report, we demonstrate that giant vesicles can grow and produce daughter vesicles by synthesizing and incorporating phospholipids in situ from ad-hoc precursors. Our model involves acyl chain elongation via copper(I)-catalyzed azide-alkyne [3 + 2] cycloaddition reaction and the ensuing production of synthetic phospholipids to induce budding and division. In addition, the growth and budding of giant vesicles were compatible with the encapsulation and transfer of macromolecules as large as lambda phage DNA to the buds. This chemical system provides a useful model towards the implementation of cell-like compartments capable of propagation and transport of biological materials.

Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()

Bookmarked The Emergence of Competition Between Model Protocells (science.sciencemag.org)
The transition from independent molecular entities to cellular structures with integrated behaviors was a crucial aspect of the origin of life. We show that simple physical principles can mediate a coordinated interaction between genome and compartment boundary, independent of any genomic functions beyond self-replication. RNA, encapsulated in fatty acid vesicles, exerts an osmotic pressure on the vesicle membrane that drives the uptake of additional membrane components, leading to membrane growth at the expense of relaxed vesicles, which shrink. Thus, more efficient RNA replication could cause faster cell growth, leading to the emergence of Darwinian evolution at the cellular level.
Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()
Bookmarked Experimental Models of Primitive Cellular Compartments: Encapsulation, Growth, and Division (science.sciencemag.org)
The clay montmorillonite is known to catalyze the polymerization of RNA from activated ribonucleotides. Here we report that montmorillonite accelerates the spontaneous conversion of fatty acid micelles into vesicles. Clay particles often become encapsulated in these vesicles, thus providing a pathway for the prebiotic encapsulation of catalytically active surfaces within membrane vesicles. In addition, RNA adsorbed to clay can be encapsulated within vesicles. Once formed, such vesicles can grow by incorporating fatty acid supplied as micelles and can divide without dilution of their contents by extrusion through small pores. These processes mediate vesicle replication through cycles of growth and division. The formation, growth, and division of the earliest cells may have occurred in response to similar interactions with mineral particles and inputs of material and energy.
Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()
Bookmarked Nonenzymatic Template-Directed RNA Synthesis Inside Model Protocells by Katarzyna Adamala (science.sciencemag.org)
The potential for self-replication makes RNA an attractive candidate as a primordial catalysis in the origin of life. Catalysis may have occurred in some kind of compartment, possibly a fatty acid vesicle. However, RNA catalysis generally requires high levels of magnesium, which are incompatible with fatty acid vesicle integrity. Adamala and Szostak (p. [1098][1]) screened magnesium chelators and found that several—including citrate, isocitrate, and oxalate—could maintain the membrane stability of fatty acid vesicles in the presence of Mg2+. Citrate also allowed Mg2+-dependent RNA synthesis within protocell-like vesicles, while at the same time protecting RNA from Mg2+-catalyzed degradation. Efforts to recreate a prebiotically plausible protocell, in which RNA replication occurs within a fatty acid vesicle, have been stalled by the destabilizing effect of Mg2+ on fatty acid membranes. Here we report that the presence of citrate protects fatty acid membranes from the disruptive effects of high Mg2+ ion concentrations while allowing RNA copying to proceed, while also protecting single-stranded RNA from Mg2+-catalyzed degradation. This combination of properties has allowed us to demonstrate the chemical copying of RNA templates inside fatty acid vesicles, which in turn allows for an increase in copying efficiency by bathing the vesicles in a continuously refreshed solution of activated nucleotides. [1]: /lookup/doi/10.1126/science.1241888

Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()

Bookmarked Origin of life: The RNA world by Walter Gilbert (Nature volume 319, page618 (1986))
UNTIL recently, when one thought of the varied molecular processes at the origin of life, one imagined that the first self-replicating systems consisted of both RNA and protein. RNA served to hold information, whereas protein molecules provided all the enzymic activities needed to make copies of RNA and to reproduce themselves. The cycle that developed a self-replicating system out of the primitive soup of amino acids and nucleotides had two radically different components.

Michael Marshall in He may have found the key to the origins of life. So why have so few heard of him? ()