arXiv subjects

Mark Leake

Publications and source records attributed to Mark Leake.

5 recordsLinked to original sources

arXiv2026

Biophysics of the Pyrenoid

Phase-separated liquid droplets organize molecules in cells, but the underlying physical principles differ from abiotic mixing and quantitative rules in living systems remain poorly understood. The pyrenoid -- a liquid-like organelle that enhances photosynthetic carbon fixation in algae and hornworts -- provides an unusually tractable model system. Here, we review recent advances in our understanding of pyrenoids from the perspective of biophysics. We highlight how reaction-diffusion models connect compartment architecture to catalytic performance, how soft matter theories link molecular interactions to condensate assembly, and how modern experimental methods enable these predictions to be tested quantitatively. Recent studies suggest that pyrenoid function may be described by a small number of effective transport and reaction processes, while condensate assembly can be understood through molecular design parameters and thermodynamic constraints. Together, these findings establish the pyrenoid as a powerful system for investigating catalytic compartmentalization, biomolecular self-organization and the emergence of effective physical descriptions in living systems.

physics.bio-ph↗

arXiv2025

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↗

arXiv2015

Innovative Science

Sir, We write as senior scientists about a problem vital to the scientific enterprise and prosperity. Nowadays, funding is a lengthy and complex business. First, universities themselves must approve all proposals for submission. Funding agencies then subject those that survive to peer review, a process by which a few researchers, usually acting anonymously, assess a proposal's chances that it will achieve its goals, is the best value for money, is relevant to a national priority and will impact on a socio-economic problem. Only 25% of proposals received by the funding agencies are funded. These protracted processes force researchers to exploit existing knowledge, severely discourage open-ended studies and are hugely time-consuming. They are also new: before 1970, few researchers wrote proposals. Now they are virtually mandatory.

physics.soc-ph↗

arXiv2015

Analytical tools for single-molecule fluorescence imaging in cellulo

Recent technological advances in cutting-edge ultrasensitive fluorescence microscopy have allowed single-molecule imaging experiments in living cells across all three domains of life to become commonplace. Single-molecule live-cell data is typically obtained in a low signal-to-noise ratio (SNR) regime sometimes only marginally in excess of 1, in which a combination of detector shot noise, sub-optimal probe photophysics, native cell autofluorescence and intrinsically underlying stochastic of molecules result in highly noisy datasets for which underlying true molecular behaviour is non-trivial to discern. The ability to elucidate real molecular phenomena is essential in relating experimental single-molecule observations to both the biological system under study as well as offering insight into the fine details of the physical and chemical environments of the living cell. To confront this problem of faithful signal extraction and analysis in a noise-dominated regime, the needle in a haystack challenge, such experiments benefit enormously from a suite of objective, automated, high-throughput analysis tools that can home in on the underlying molecular signature and generate meaningful statistics across a large population of individual cells and molecules. Here, I discuss the development and application of several analytical methods applied to real case studies, including objective methods of segmenting cellular images from light microscopy data, tools to robustly localize and track single fluorescently-labelled molecules, algorithms to objectively interpret molecular mobility, analysis protocols to reliably estimate molecular stoichiometry and turnover, and methods to objectively render distributions of molecular parameters

q-bio.BM↗

arXiv2012

Inferring diffusion in single live cells at the single molecule level

The movement of molecules inside living cells is a fundamental feature of biological processes. The ability to both observe and analyse the details of molecular diffusion in vivo at the single molecule and single cell level can add significant insight into understanding molecular architectures of diffusing molecules and the nanoscale environment in which the molecules diffuse. The tool of choice for monitoring dynamic molecular localization in live cells is fluorescence microscopy, especially so combining total internal reflection fluorescence (TIRF) with the use of fluorescent protein (FP) reporters in offering exceptional imaging contrast for dynamic processes in the cell membrane under relatively physiological conditions compared to competing single molecule techniques. There exist several different complex modes of diffusion, and discriminating these from each other is challenging at the molecular level due to underlying stochastic behaviour. Analysis is traditionally performed using mean square displacements of tracked particles, however, this generally requires more data points than is typical for single FP tracks due to photophysical instability. Presented here is a novel approach allowing robust Bayesian ranking of diffusion processes (BARD) to discriminate multiple complex modes probabilistically. It is a computational approach which biologists can use to understand single molecule features in live cells.

q-bio.QM↗