Final Report Summary - AUTO-EVO (Autonomous DNA Evolution in a Molecule Trap)
Can we understand how live emerged on early earth? We could experimentally show how the early geology of earth could have harbored and developed the first living systems. Our experiments are implementing all aspects of the first living molecules by using a very simple nonequilibrium driving, namely a temperature gradient. A thermal difference across a microscale pore can drive all central aspects of molecular evolution: feeding, selection pressure towards longer RNA, replication by thermal cycling, active accumulation of molecules by thermophoresis and open outflow of unused molecules.
These are conditions which you find everywhere on a volcanic earth, namely porous rock where either hot water or possibly more importantly, hot steam is creating local gradients. In short, we could find a boundary condition which could harbor the first life - and demonstrate in the lab using a PCR reaction. This is the starting point for a wide range of interesting molecular evolution experiments - and a testbed to implement future prebiotic chemistry of RNA, amino acid creation and ligation.
In more detail, the thermal gradient across a rock pore implements in a continuous, autonomous fashion all major points necessary for the evolution of the first molecules: (i) thermophoresis and convection accumulate molecules from very low concentrations in water without the need for evaporation, (ii) a through-flow is feeding the reactor pore continuously while still accumulating molecules from the flow, (iii) thermophoresis and through-flow implements a very selective length filter keeping longer DNA inside the trap, (iv) separation of double stranded DNA into single strands by the thermal oscillation of convection in the thermal gradient, (v) demonstration of replication and selection towards more complex molecules against the well known tyranny of the shortest of Spiegelman. All this is purely driven by a thermal gradient in a porous rock. The latest experiment showing (i)-(v) has been published in Nature Chemistry in 2015 [doi:10.1038/nchem.2155].
Towards the implementation of RNA-based evolution, we made a big step in showing that the thermal trap from convection and thermophoresis is strongly pushing any polymerization equilibrium - for example RNA, but the effect is general and should also apply for peptides - towards very long strands, published in PNAS in 2013 [doi:10.1073/pnas.1303222110]. The expectation is that exceedingly long structures are formed and perhaps even push by a thermal gradient towards a phase transition. So we are now in a very good position to explore prebiotic chemistry in the same setting for autonomous evolution and the transition from dead to living, i.e. evolving systems.
Moreover we could demonstrate that a pool of tRNA-molecule - probably our oldest fossil in molecular evolution - could be used in a thermal cycling to perform a very basic replication dynamics: copying an assembly of tRNA into free flowing tRNA molecules and also make them incorporate the initial assembly. A possible outcome of this replication dynamics is the translation itself. This was published in PRL in 2012 [doi:10.1103/PhysRevLett.108.238104].
Besides, we continued to understand the mechanisms behind thermophoresis and foster new ways to apply this technique to medicine and pharmaceutical development, spearheaded by our very successful startup company Nanotemper. Their machines are now found in biochemistry labs worldwide and has spread our technology in a way you do not see in terms of pure citations.
These are conditions which you find everywhere on a volcanic earth, namely porous rock where either hot water or possibly more importantly, hot steam is creating local gradients. In short, we could find a boundary condition which could harbor the first life - and demonstrate in the lab using a PCR reaction. This is the starting point for a wide range of interesting molecular evolution experiments - and a testbed to implement future prebiotic chemistry of RNA, amino acid creation and ligation.
In more detail, the thermal gradient across a rock pore implements in a continuous, autonomous fashion all major points necessary for the evolution of the first molecules: (i) thermophoresis and convection accumulate molecules from very low concentrations in water without the need for evaporation, (ii) a through-flow is feeding the reactor pore continuously while still accumulating molecules from the flow, (iii) thermophoresis and through-flow implements a very selective length filter keeping longer DNA inside the trap, (iv) separation of double stranded DNA into single strands by the thermal oscillation of convection in the thermal gradient, (v) demonstration of replication and selection towards more complex molecules against the well known tyranny of the shortest of Spiegelman. All this is purely driven by a thermal gradient in a porous rock. The latest experiment showing (i)-(v) has been published in Nature Chemistry in 2015 [doi:10.1038/nchem.2155].
Towards the implementation of RNA-based evolution, we made a big step in showing that the thermal trap from convection and thermophoresis is strongly pushing any polymerization equilibrium - for example RNA, but the effect is general and should also apply for peptides - towards very long strands, published in PNAS in 2013 [doi:10.1073/pnas.1303222110]. The expectation is that exceedingly long structures are formed and perhaps even push by a thermal gradient towards a phase transition. So we are now in a very good position to explore prebiotic chemistry in the same setting for autonomous evolution and the transition from dead to living, i.e. evolving systems.
Moreover we could demonstrate that a pool of tRNA-molecule - probably our oldest fossil in molecular evolution - could be used in a thermal cycling to perform a very basic replication dynamics: copying an assembly of tRNA into free flowing tRNA molecules and also make them incorporate the initial assembly. A possible outcome of this replication dynamics is the translation itself. This was published in PRL in 2012 [doi:10.1103/PhysRevLett.108.238104].
Besides, we continued to understand the mechanisms behind thermophoresis and foster new ways to apply this technique to medicine and pharmaceutical development, spearheaded by our very successful startup company Nanotemper. Their machines are now found in biochemistry labs worldwide and has spread our technology in a way you do not see in terms of pure citations.