Reading and writing digital information in TNA
DNA molecules have become a popular information storage system but are
susceptible to degradation in a cell-like environment. In this paper, the
authors suggest the use of the unnatural genetic framework based on TNA. The
backbone structure of this unnatural genetic polymer is recalcitrant to
nuclease digestion. 23 kilobytes of digital information were stored in TNA and
recovered with perfect accuracy after exposure to biological nucleases that
destroyed equivalent DNA messages.
https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00361
Metastable hybridization-based DNA information storage to allow rapid
and permanent erasure
The authors argue that data stored in DNA in the traditional manner is
hard to wipe clean - it requires enzymes, UV or extreme heat. They propose a
stable but easily-erasable memory, in which single strands carry a memory
location domain and the actual contents of the memory. Multiple distinct
strands with the same memory location domain are included, but only one is
prepared with a "truth" flag (a strand that is complementary to
the memory location domain) whilst the rest are prepared with "false"
flags (chemically modified strands). Data can be read out by performing PCR on
the system, since the modified strands that constitute the false flags cannot
be extended. Data can be easily wiped through a short heating protocol, which
will randomise the flags very quickly. While the method achieves this
functionality pretty well, it is limited - there is no scope to erase and then
re-write data, for example.
https://www.nature.com/articles/s41467-020-18842-6
Exponential volume dependence of entropy-current fluctuations at
first-order phase transitions in chemical reaction networks
In this paper, the divergence of the fluctuations of a chemical switch
as a function of system size is quantified and a critical exponent is
calculated. The chemical reaction scheme of Schlögl model is studied. Here, the
steady state number of a certain chemical species X displays a first order
phase transition as the reaction rates are varied. This paper uses various
methods to analyse the chemical master equation (CME) at the transition and
calculate the variance to find an exponential dependence on system size with a
given exponent. This provides a very readable example of a few methods to
analyse CMEs.
https://journals.aps.org/pre/abstract/10.1103/PhysRevE.102.022101
Single-particle cryo-EM at atomic resolution
Cryogenic electron microscopy is used to determine the atomic-scale
structure of biomolecules without needing to form a crystal of the sample, as
is required for x-ray crystallography. In single-particle cryo-EM, a sample
containing a high concentration of the molecule of interest is flash frozen and
imaged repeatedly with a beam of single electrons. The scattered electrons,
that are captured by a camera, form an image of the sample which is used to
reconstruct the shape of the molecule of interest. Here the authors report
three improvements that brought the resolution of cryo-EM below 2 Angstroms; an
electron source with a narrow energy spread that reduced chromatic aberrations,
a more effective energy filter that can separate out useful elastically and useless
inelastically scattered electrons, and an advanced camera and reconstruction
algorithm capable of capturing scattered electrons with high spatio-temporal
resolution. In a reconstruction of a 5-fold symmetric human membrane channel
protein, small molecule coordination, alternative amino acid conformations and
side chain variations were resolved. Further, using an advanced reconstruction
method of a 24-fold symmetric mouse protein, the scattering potential of
hydrogen atoms could be resolved in the most ordered parts of the structure,
enabling analysis of the hydrogen-bonding network in the protein. Atomic
resolution cryo-EM will provide insights into the mechanical function of
biomolecules and improve structure-based drug discovery.
https://www.nature.com/articles/s41586-020-2829-0
The evolution of DNA-templated synthesis as a tool for materials
discovery
Control of reactivity and product structure is one of the main challenges
during the design of chemical reactions. A method to introduce said control is
DNA-templated synthesis (DTS), where DNA-bound chemicals are assembled over a
complementary DNA strand that acts as a template. The focus of this review is
the potential application of DTS for the directed evolution of chemicals, by
several cycles of template mutation and selection. The authors enumerate all
the possible DTS mechanisms that allow the implementation of selection cycles,
the chemical reactions templated with said mechanisms, and the challenges they
face.
https://pubs.acs.org/doi/10.1021/acs.accounts.7b00280
Nanopore-based DNA hard drives for rewritable and secure data storage
Solid-state nanopores have been
demonstrated to be powerful molecular sensors for detecting nanoscale objects.
In this article, a long DNA scaffold is use as a “hard drive” to write, erase,
and rewrite data on, and read it out by passing the strand through a
solid-state nanopore. The data sites are functionalised with small
DNA-overhangs which can be hybridised with unique complementary biotinylated
strands. The unhybridised and hybridised strands generate weaker and stronger
current signals respectively when passed through the nanopore which can be read
as 0 or 1. Thus, a combination of data sites can encode meaningful data in binary
format. To erase the data, another fuel strand is added which utilises a short
toehold at the end of the biotynilated strands to detach it from the overhangs
which can be reused again to encode different data. To refine this approach,
the group has also demonstrated the utilization of two separate encoding sites
(address sites and data sites) simultaneously to encode both the data and its
sequence. Moreover, they showed the use of a physical “key” to encrypt the data
on the DNA hard drive without which the readout does not match the actual
encoded data.
https://pubs.acs.org/doi/full/10.1021/acs.nanolett.0c00755
Toehold-mediated strand displacement reaction for dual-signal electrochemical assay of Apolipoprotein E genotyping
Apolipoprotein E (ApoE) is a polymorphic gene which has been identified as an important genetic determinant for Alzheimer's disease. In the human population six genotypes of ApoE exist, with distinct risks associated with each. In this paper, the authors developed a toehold-mediated strand displacement-based approach to genotype ApoE. Using an electrochemical detection system, the authors could detect the presence of absense of mutations at 2 codons within the gene. This system allowed for systematic characterisation of ApoE genotype.
https://pubs.acs.org/doi/pdf/10.1021/acssensors.0c01511
They developed a polymer-peptide conjugate that forms nanoscale sphere at normal pH. The polymer gets uptaken by cancer cells. When the polymer is at the endosome, it changes conformation to micrometre sized sheet and destroys the endosome. Then the peptide gets presented outside of the cell to trigger an inflammation response.
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