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.
https://www.sciencedirect.com/science/article/pii/S0022519321002411
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.
https://pubs.acs.org/doi/pdf/10.1021/acssynbio.1c00062
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.
https://www.sciencedirect.com/science/article/pii/S073497501000025X
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.
https://aip.scitation.org/doi/10.1063/1.4923066
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.
https://academic.oup.com/nar/article/49/11/6114/6298617
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