Departmental news
Engineering stress as a motivation for filamentous virus morphology
An image representing the work of Dr Nicole Robb et al made the cover of Biophysical Reports!
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EnteroBase in 2025: exploring the genomic epidemiology of bacterial pathogens
This paper presents an update on the content, accessibility and analytical tools of the EnteroBase platform for web-based pathogen genome analysis. EnteroBase provides manually curated databases of genome sequence data and associated metadata from currently >1.1 million bacterial isolates, more recently including Streptococcus spp. and Mycobacterium tuberculosis, in addition to Salmonella, Escherichia/Shigella, Clostridioides,Vibrio,Helicobacter,Yersinia and Moraxella.
A temperature-induced metabolic shift in the emerging human pathogen Photorhabdus asymbiotica
The Photorhabdus bacterial genus contains both human and insect pathogens, and most of these species cannot grow in higher temperatures. However, Photorhabdus asymbiotica, which infects both humans and insects, can grow in higher temperatures and undergoes metabolic adaptations at a temperature of 37°C compared to that of insect body temperature. Therefore, it is important to examine how this bacterial species can metabolically adapt to survive in higher temperatures. In this paper, using a mathematical model, we have examined the metabolic shift that takes place when the bacteria switch from growth conditions in 28°C to 37°C. We show that P. asymbiotica potentially experiences predicted temperature-induced metabolic adaptations at 37°C predominantly clustered within the nucleotide metabolism pathway. Such information is important to understand how bacterial pathogens adapt to human infection. Read the paper hereLink opens in a new window.
Novel real-time automation of combined frequency and low voltage substrate mapping to guide ablation for Brugada syndrome: a case report
Brugada syndrome (BrS) is an inherited cardiac condition that increases the risk of sudden cardiac death (SCD) due to ventricular arrhythmias. Catheter ablation has been shown to effectively reduce recurrent ventricular fibrillation (VF) episodes through targeting of abnormal electrograms predominantly located within the anterior surface of the right ventricular outflow tract. Signal frequency mapping is an emerging concept that provides further definition of pathological ventricular substrate.
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Genome wide analysis revealed conserved domains involved in the effector discrimination of bacterial type VI secretion system
Type VI secretion systems (T6SS) inject protein effectors directly into the cytoplasm of target cells. The T6SS is important for activities as diverse as bacterial pathogenicity, symbiosis, and inter-bacterial competition. Nevertheless, questions remain as to how the so many diverse toxins can be selected for injection by the T6SS. This study presents a searchable online database of all examples of a specific critical component of all T6SS, VgrG. This protein is a “spike” that allows the system to puncture host membranes and deliver the effector. An additional “adapter” protein is required to link the effector to the VgrG. Our database allowed us to determine six domain families encoded within vgrG loci important in the selection process. This work should facilitate other researchers in the field to better understand what effector proteins they use and how they are selected by the T6SS. Read the paper here.Link opens in a new window
Detailed Analysis of Electrogram Peak Frequency to guide Centricular Tachycardia Substrate Mapping
Professor Tarvinder Dhanjal, Professor of Cardiology, has had their latest manuscript published in EP Europace journal. The project was a multi-centre, international, mechanistic VT mapping study including UHCW, Brighton and Barcelona.
Abstract:
Differentiating near-field (NF) and far-field (FF) electrograms (EGMs) is crucial in identifying critical arrhythmogenic substrate during Ventricular Tachycardia (VT) ablation. A novel algorithm annotates NF fractionated signals enabling EGM Peak Frequency (PF) determination using wavelet transformation. This study evaluated the algorithms effectiveness in identifying critical components of the VT circuit during substrate mapping.
Read the paper here.
Insight into the emerging insect to human pathogen Photorhabdus revealing geographic differences in immune cell tropism
In this study, we investigate the differences between the pathogenic activities of P. asymbiotica isolates from different geographic locations. Pathogenicity was analysed using infection assays with both cultured cell lines (THP-1, CHO, and HEK cells) and primary immune cells, and peripheral blood mononuclear cells (PBMCs) isolated from human blood.
Single-cell analysis identifies distinct macrophage phenotypes associated with prodisease and proresolving functions in the endometriotic niche
Endometriosis negatively impacts the health-related quality of life of 190 million women worldwide. Novel advances in nonhormonal treatments for this debilitating condition are desperately needed. Macrophages play a vital role in the pathophysiology of endometriosis and represent a promising therapeutic target. In the current study, we revealed the full transcriptomic complexity of endometriosis-associated macrophage subpopulations using single-cell analyses in a preclinical mouse model of experimental endometriosis. We have identified two key lesion-resident populations that resemble i) tumor-associated macrophages (characterized by expression of Folr2, Mrc1, Gas6, and Ccl8+) that promoted expression of Col1a1 and Tgfb1 in human endometrial stromal cells and increased angiogenic meshes in human umbilical vein endothelial cells, and ii) scar-associated macrophages (Mmp12, Cd9, Spp1, Trem2+) that exhibited a phenotype associated with fibrosis and matrix remodeling. We also described a population of proresolving large peritoneal macrophages that align with a lipid-associated macrophage phenotype (Apoe, Saa3, Pid1) concomitant with altered lipid metabolism and cholesterol efflux. Gain of function experiments using an Apoe mimetic resulted in decreased lesion size and fibrosis, and modification of peritoneal macrophage populations in the preclinical model. Using cross-species analysis of mouse and human single-cell datasets, we determined the concordance of peritoneal and lesion-resident macrophage subpopulations, identifying key similarities and differences in transcriptomic phenotypes. Ultimately, we envisage that these findings will inform the design and use of specific macrophage-targeted therapies and open broad avenues for the treatment of endometriosis.
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Single molecule dynamics in a virtual cell combining a 3-dimensional matrix model with random walks
Professor Justin Molloy has a new paper in the journal "Scientific Reports" in collaboration with Gregory I. Mashanov of the Francis Crick institute, London.
The paper describes a multiscale computer model that simulates the dynamics of individual molecules within the complex architecture of a living cell.
Biological molecules show dynamic changes in structure and position over a very wide range of time and length scales - from nanoseconds to tens of seconds and nanometres to tens of micrometres. These dynamic ranges can be difficult to capture, simulate and model. We present a multiscale modelling environment that helps to bridge the gap between time and length scales and model experimental data sets using relatively simple physical-chemical understandings of molecular interactions and thermal forces.
Receptor binding and tortuosity explain morphogen local-to-global diffusion coefficient transition
In this work, we explored how molecules (e.g., morphogens) move within biologically realistic domains. Our Singapore-based collaborators (Wohland lab) generated subcellular resolution maps of the developing zebrafish hindbrain using electron microscopy. Yi Ting Loo, a MathSys PhD student in the Saunders lab, built a simulation environment to explore how molecules would move within these maps. We accounted for tortuosity, dead-ends and receptor binding. Our results reveal how measurement techniques such as FCS and FRAP can lead to very different estimations of dynamic parameters (e.g., the diffusivity). Hopefully, this work provides a framework for properly accounting for biologically complex environments in estimating dynamics in living organisms.
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