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Jack Shepherd

Publications and source records attributed to Jack Shepherd.

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Invention, Innovation, and Commercialisation in British Biophysics

British biophysics has a tradition of scientific invention and innovation, resulting in new technologies transforming biological insight, such as rapid DNA sequencing, super-resolution and label-free microscopy, high-throughput and single-molecule bio-sensing, and bio-inspired synthetic materials. Some advances were established through democratised platforms and many have biomedical success, a key example involving the SARS-CoV-2 spike protein during the COVID-19 pandemic. Here, three UK labs made crucial contributions revealing how the spike protein targets human cells, and how therapies of vaccines and neutralizing nanobodies work, enabled largely through biophysical innovations of cryo-electron microscopy. Here, we discuss leading-edge innovations which resulted from discovery-led British 'Physics of Life' research (capturing blends of physical-life sciences research in the UK including biophysics and biological physics) and have matured into wide-reaching sustainable commercial ventures enabling translational impact. We describe the biophysical science which led to these academic spinouts, presenting the scientific questions that were addressed through innovating new techniques and approaches. We consider these examples through the lens of opportunities and challenges for academic biophysics research in partnership with British industry. We highlight how commercial breakthroughs have emerged organically from fundamental research rather than from technology-first approaches but also discuss lessons to learn from past failures. Finally, we propose recommendations concerning future resourcing and structuring of UK biophysics research and the training and support of its researchers to ensure that UK plc punches above its weight in biophysics innovation, and a need to educate the policymakers and public that an absence of basic science impoverishes innovation.

physics.bio-ph

Single-molecule techniques in biophysics: a review of the progress in methods and applications

Single-molecule biophysics has transformed our understanding of the fundamental molecular processes involved in living biological systems, but also of the fascinating physics of life. Far more exotic than a collection of exemplars of soft matter behaviour, active biological matter lives far from thermal equilibrium, and typically covers multiple length scales from the nanometre level of single molecules up several orders of magnitude to longer length scales in emergent structures of cells, tissues and organisms. Biological molecules are often characterized by an underlying instability, in that multiple metastable free energy states exist which are separated by energy levels of typically just a few multiples of the thermal energy scale of kBT, where kB is the Boltzmann constant and T the absolute temperature, implying complex, dynamic inter-conversion kinetics across this bumpy free energy landscape in the relatively hot, wet environment of real, living biological matter. The key utility of single-molecule biophysics lies in its ability to probe the underlying heterogeneity of free energy states across a population of molecules, which in general is too challenging for conventional ensemble level approaches which measure mean average properties. Parallel developments in both experimental and theoretical techniques have been key to the latest insights and are enabling the development of highly-multiplexed, correlative techniques to tackle previously intractable biological problems. Experimentally, technological developments in the sensitivity and speed of biomolecular detectors, the stability and efficiency of light sources, probes and microfluidics, have enabled and driven the study of heterogeneous behaviours both in vitro and in vivo that were previously undetectable by ensemble methods...

physics.bio-ph