Thursday, 5 May 2022

Exploiting and understanding cellular molecules: nucleic acids and proteins

Strategies for Constructing and Operating DNA Origami Linear Actuators

The authors discuss the protocol optimisation for the fabrication of a DNA origami rotaxane. The objective is to find the protocol that produces the highest yield of working rail/sliders systems to use as linear actuators on the nanometric scale. The use of these sliders, when combined, will allow the fabrication of materials with subnanometer precision using the slider as a “printing head”.

A tractable genotype–phenotype map modelling the self-assembly of protein quaternary structure

The polyomino model is introduced as a high-level model of assembly of protein sub-domains into larger complexes. The paper introduces the fundamental features of the polyomino model, starting with the genotype to the formation of individual assembly kits and finally the formation of complete structures from assembly kits. The paper investigates polyominos within the wider context of genotype-phenotype maps, with regards to genotype redundancy, phenotype bias, component disconnectivity, shape space covering, as well as phenotypic robustness and its relationship to evolvability, and finds that these are quite similar to the RNA folding GP map. From a GP map perspective, this raises the question of whether these traits are inherent to self-assembling systems. Eventually, the polyomino model could yield insights on artificial systems like DNA tiles.

Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities

The researchers create a paper based lateral flow devices based on Loop-mediated isothermal amplification (LAMP) of DNA. Although, PCR-based amplification assays remain the gold-standard NAAT, the requirement for trained staff and external power has limited their application in areas with reduced resources. LAMP has recently emerged as easy-to-use alternatives to PCR, owing to greatly simplified hardware requirements.

The paper discusses use of paper origami techniques to prepare blood sample preparation (including magnetic beads on DNA molecules of interest), followed by the LAMP process in a small microfluidic chamber. A hand pressed button initiates lateral flow of the amplified DNA that travels along a small membrane where anti-FITC antibodies and immobilized streptavidin are present as test and control lines. Upon successful attachment of species-specific ligands to anti-FITC antibodies, a positive signal is generated thereby enabling detection of diseases.

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