Biology subjects

Hiscock, J. R.

Publications and source records attributed to Hiscock, J. R..

4 recordsLinked to original sources

bioRxiv2022

Next generation protein-based materials capture and preserve projectiles from supersonic impacts

Extreme energy dissipating materials are essential for a range of applications. The military and police force require ballistic armour to ensure the safety of their personnel, while the aerospace industry requires materials that enable the capture, preservation and study of hypervelocity projectiles. However, current industry standards display at least one inherent limitation. To resolve these limitations we have turned to nature, utilising proteins that have evolved over millennia to enable effective energy dissipation. Specifically, a recombinant form of the mechanosensitive protein talin was incorporated into a monomeric unit and crosslinked, resulting in the production of the first reported example of a talin shock absorbing material (TSAM). When subjected to 1.5 km/s supersonic shots, TSAMs were shown not only to absorb the impact, but to capture/preserve the projectile, making TSAMs the first reported protein material to achieve this.

synthetic biology↗

bioRxiv2022

Elucidation of small molecule passive permeation across lipid membranes using conventional solution state NMR methods

Quantifying small molecule uptake across a biological membrane in any cell system is crucial for the development of efficacious and selective drugs. However, obtaining such data is not trivial, especially in bacterial systems. Herein, we present an assay which enables the determination of the degree of passive permeation and membrane interaction of mixtures of small molecules in vesicles of a desired lipid composition, including that of bacterial membranes. The assay employs highly accessible conventional solution NMR experiments, exploiting the paramagnetic relaxation enhancement effect, and allows the measurement of membrane permeation on mixtures of any number of small molecules which do not exhibit heterogeneous molecular signal overlap in under 20 minutes. As a proof-of -principle we apply this methodology to candidates from a class of supramolecular self-associating amphiphiles, members from which have been shown to interact with biological phospholipid membranes and elicit an antimicrobial effect, allowing the determination and comparison of their membrane permeability and membrane interaction properties.

biophysics↗

bioRxiv2022

Exceptional yield vesicle packaged recombinant protein production from E. coli.

We describe a novel system that exports diverse recombinant proteins in extracellular vesicles from E. coli. The vesicles not only compartmentalise toxic, insoluble and disulphide bond containing proteins in a soluble and functional form (e.g. DNaseI, nanobodies and IgG-fusions), but the continued release of the inducible vesicle packaged proteins into the media supports continuous isolation of protein from active culture within a micro-environment allowing stable long-term storage. This technology results in unprecedented yields of vesicle packaged functional proteins for efficient downstream processing for a wide range of applications from discovery science to applied biotechnology and medicine.

molecular biology↗

bioRxiv2020

Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles

Amyloid seeds are nanometre-sized protein particles that accelerate amyloid assembly, as well as propagate and transmit the amyloid protein conformation associated with a wide range of protein misfolding diseases. However, seeded amyloid growth through templated elongation at fibril ends cannot explain the full range of molecular behaviours observed during cross-seeded formation of amyloid by heterologous seeds. Here, we demonstrate that amyloid seeds can accelerate amyloid formation via a surface catalysis mechanism without propagating the specific amyloid conformation associated with the seeds. This type of seeding mechanism is demonstrated through quantitative characterisation of the cross-seeded assembly reactions involving two non-homologous and unrelated proteins: the human A{beta}42 peptide and the yeast prion-forming protein Sup35NM. Our results suggest experimental approaches to differentiate seeding by templated elongation from non-templated amyloid seeding, and rationalise the molecular mechanism of the cross-seeding phenomenon as a manifestation of the aberrant surface activities presented by amyloid seeds as nanoparticles.

biochemistry↗