Saturday, 10 July 2021

The role of strand displacement: from the origin of life to current perspectives

Rolling-circle and strand-displacement mechanisms for non-enzymatic RNA replication at the time of the origin of life

Tupper and Higgs use basic chemical reasoning illustrated with ODE-level modelling to argue that pre-enzymatic replication of RNA templates would have been most successful in a "rolling circle displacement" mode, wherein a circular template is copied by a product that displaces its own tail as it goes round the template. This tail must eventually be cleaved by some kind of self-cleaving ribozyme, and ligated to form another circular template for the reaction to proceed to another generation. The authors argue that a displacement mechanism is the only way to avoid suppression of the reaction via product inhibition, wherein copies bind strongly to their templates. Going further than previous arguments, they claim that even in systems with time varying external conditions that allow separation and synthesis in different environments, products will still cause inevitable inhibition through rebinding at a critical concentration. This critical concentration is relatively low because pre-enzymatic extension of RNA on a template would have been slow. Moreover, rolling circle displacement is deemed to be better than displacement on a linear template, because linear templates suffer from the fact that the strand that is being synthesised can be easily displaced from the template at each (slow) synthesis step.

DNA computing: NOT logic gates see the light

This paper describes a NOT gate for DNA computation enabled by optical control of nucleic acid function via light-removable nucleobase caging groups. This temporal precise control using light allowed the authors the introduction of Boolean logic gates into single- and multilayer DNA circuits. The design was successfully integrated within NOT, NOR and NAND circuits demonstrating the potential of DNA circuitry.

Reactor design for minimizing product inhibition during enzymatic lignocellulose hydrolysis
II. Quantification of inhibition and suitability of membrane reactors

This review discusses the effect of product inhibition in the particular case of lignocellulose hydrolysis. The authors present ways of quantifying and experimentally characterise the inhibition and propose reactor designs that can minimise the product inhibition effect of the enzymatic reaction.

Perspective: Sloppiness and emergent theories in physics, biology, and beyond

This paper aims to utilise information geometry to simplify models with a large number of parameters. They make the point that in such models with many parameters, there are often multiple combinations of parameters which fit the model and that certain subsets of parameters make little difference to the predictions. This is made more formal by looking at the Fisher Information matrix (FIM) made from the parameters and finding that its eigenvalues have a roughly exponential structure, where the second largest is an order of magnitude smaller than the largest etc. This means only a few eigenvalues are relevant. Information geometry focusses on using the FIM as a Riemannian metric on the manifold of parameters. Due to the exponential structure of the eigenvalues the manifold has a ribbon like structure with boundaries corresponding to simplifications of the model. Certain combinations of parameters having little effect on the predictions translates into certain directions in parameter space being irrelevant. Following these directions to a boundary helps to simplify models. They give the specific example of a metabolic pathway being reduced from 48 parameters to 12.

Kinetics of heterochiral strand displacement from PNA-DNA heteroduplexes

DNA comes in two distinct enantiomers (L-DNA and D-DNA). These enantiomers can not form base pairs with each other. This paper develops a reaction known as heterochiral strand displacement which allows displacement of one enantiomer by the other using an achiral substrate strand made from PNA. This study undertakes an extensive characterisation of the kinetics of heterochiral strand displacement across a range of toehold lengths and mismatch positions. Heterochiral strand displacement is particularly useful when considering introduction of nanodevices into cells, as L-DNA will not interfere with native cellular molecules or be recognised by nucleases.

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