Monday 9 December 2019

Reading list from 2/12/2019:Cahos with no equilibrium, cellular supremacy, nanoclocks, and new ways to probe molecular systems

Dynamical behaviors of a chaotic system with no equilibria 
https://www.sciencedirect.com/journal/physics-letters-a/vol/376/issue/2

A relatively simple three-variable autonomous system of ordinary differential equations (ODEs) is presented, which, depending on the choice of the underlying parameters, displays zero, one or two stationary (equilibrium) points. Using Liapunov exponents, bifurcation diagrams and Poincare maps, the system is shown to display chaotic attractors, whose nature depends on the number of the underlying equilibria. In particular, the system displays a chaotic attractor even in the absence of equilibria.


Pathways to cellular supremacy in biocomputing
https://www.nature.com/articles/s41467-019-13232-z

In the present article, the authors try to settle a new perspective with regards synthetic biology by defining the notion of cellular supremacy as the  circumstance in which the implementation and execution of an algorithm would be tractable in a reasonable amount of time only in a cellular substrate rather than on a silicon microchip (akin to the notion of quantum supremacy). The authors acknowledge that analogies with the Boolean algebra logic underlying all digital computing have been used in biology since the time of Jacques Monod, but they argue that all cellular systems have a series of features (massive parallel exploration of all the space of solutions, use of stochasticity for synchronization and optimization of resources, analog signal treatment, concurrency of computational agents as well as the possibility of dealing with the increasing complexity of algorithms distributing them in cellular consortia) that put them far away from conventional computing paradigms and could lead the way to the aforementioned supremacy.


Bilingual Peptide Nucleic Acids: Encoding the Languages of Nucleic Acids and Proteins in a Single Self-Assembling Biopolymer
https://pubs.acs.org/doi/10.1021/jacs.9b09146

Peptide nucleic acids (PNA) are DNA/RNA mimic molecules comprising a sequence of nucleic acids joined by a peptide, rather than a de/oxyribose phosphate, backbone. PNA polymers acan exploit both the sequence-specific complementarity of the nucleotides as well as the complex chemistry of proteins. In this paper, PNA polymers were constructed with poly-peptide chain appendages, one half of which was hydrophobic and the other half hydrophilic. A fluorescent tag was attached to the hydrophobic end that increases in intensity in increasingly hydrophobic environments. The hydrophilic/phobic appendage drove the system of PNA molecules to self assemble into vesicles which, due to the accumulation of fluorophores in a hydrophobic region, had high fluorescence intensity at their centre. Upon addition of a disease-related RNA (the complement of the pre-designed PNA molecule's nucleotide sequence), binding between the PNA and the RNA destabilised the vesicles and disassembly was observed using TEM. This system brings together the highly directable chemistry of nucleotides and the structural versatility of proteins to create dynamical structures that can be triggered by their environment. The authors look to extend this system to generate many other tertiary structures using different polypeptide chains.


A rotary plasmonic nanoclock
https://www.nature.com/articles/s41467-019-13444-3
DNA-origami structures can be conjugated with metallic nanoparticles to localize them at defined positions to produce specific photoelectric effects. However, current structures are static or can only alternate between two states. This paper introduces a conjugated DNA structure that resembles a clock. The hands of this nanoclock are formed by a gold nanorod that can rotate 360 degrees with respect to an static gold nanorod. The different degrees of the rod rotation are determined by arbitrary binding points in the DNA structure and by the addition of specific strands in the solution.


A multiplexed, electrochemical interface for gene-circuit-based sensors
https://www.nature.com/articles/s41557-019-0366-y
This paper describes the first electrochemical interface that allows expanded multiplexed reporting for cell-free gene-circuit-based sensors. The authors were able to activate gene circuits using DNA nanostructured microelectrodes as electrochemical detectors. This approach uses toehold switch-based RNA sensors, which, in the presence of corresponding trigger RNA, express one of ten restriction-enzyme-based reporters to catalyse the release of specific reporter DNA. This single-stranded DNA can interact with its complementary ssDNA that is conjugated to the electronic surface. A redox reporter molecule attached to the reporter DNA is close enough to an electrode surface to produce generate an electrochemical signal. Thus, each toehold switch is engineered to produce a unique restriction-enzyme-based reporter that is coupled to a distinct reporter DNA and capture DNA pair for multiplexed signalling. The authors demonstrated with this work the power of the electrochemical interface by detecting the activation of specific toehold switch-based RNA sensors allowing to distinct and multiplexed signals to operate without crosstalk.


Thermodynamics guided strand-displacement-based DNA probe for determination of the average methylation levels of multiple CpG sites
https://pubs.acs.org/doi/10.1021/acs.analchem.9b03198
The authors measured the average degree of methylation using a mismatch-driven shift in the output of strand-displacement reactions. The substrate DNA was amplified with bisulfite PCR which changes non-methylated T base into A base which creates mismatches that participate in the strand displacement process.