Latest Publications
Engineered bacteriophages for therapeutic and diagnostic applications
Kandas Traore, Damien Seyer, Agnes Mihajlovski, Antonia P Sagona
Antimicrobial resistance represents one of the most serious threats to both public health and economic sustainability. One of the promising approaches to address this problem is phage therapy – treatment of pathogenic bacterial infections using bacteriophages. Bacteriophages have a narrow host spectrum of activity, minimal side effects and self-replication at the infection site, which positions them as promising candidates to complement or replace conventional antibiotics. Moreover, they can be easily genetically modified to enhance their effectiveness and safety. In this At a Glance article, we highlight the timely relevance of engineered phages as an innovative solution in a rapidly evolving healthcare landscape. First, we introduce bacteriophages' life cycle, ecology and therapeutic history, emphasizing their role in One Health strategies. Then, we describe advanced engineering techniques that can be used to expand bacteriophages' functionalities. Finally, we discuss innovative applications of engineered bacteriophages in biotechnological applications and as a potential countermeasure for antimicrobial resistance, including serving as a shuttle for delivering genes and drugs to the targeted bacterial and eukaryotic cells, targeting intracellular bacteria, contributing to vaccine development, facilitating advancements in tissue engineering and improving bacteriophages' antibacterial properties.
Developmental fates and N2-fixing efficiency of terminally-differentiated versus undifferentiated bacteroids from legume nodules
Carmen Sánchez-Cañizares , Raphael Ledermann , Joseph McKenna, Thomas J Underwood , Marcela Mendoza-Suárez , Rob Green , Karunakaran Ramakrishnan , Alison K East , Isabel Webb , Charlotte Kirchhelle , Beatriz Jorrín , Gerhard Saalbach , Euan K James , Flavia Moreira-Leite , Jason Terpolilli , Philip S Poole
Within legume root nodules, rhizobia differentiate into bacteroids, which reduce N2 into NH3 for secretion to the plant. Bacteroids may be swollen and terminally differentiated or non-swollen and can regenerate outside nodules. It is unclear why these different endosymbiotic lifestyles exist and whether they differ in symbiotic efficiency. Here, we compared N2 fixing bacteroids of the near isogenic strains Rhizobium leguminosarum bv. phaseoli 4292 (Rlp4292) and R. leguminosarum bv. viciae A34 (RlvA34), nodulating Phaseolus vulgaris (common bean) and Pisum sativum (pea), respectively. The larger bean plants fixed more N2, but peas fixed 1.6-3-fold more per unit nodule mass. Values per unit volume were similar between bean and pea because bean nodules are 2.7-fold denser (i.e., mass per unit volume). Bean nodules have higher numbers of smaller (∼1/5 the volume) bacteroids than peas. Bean bacteroids are denser (i.e., 2.5-fold protein per unit volume) although less closely packed than pea bacteroids (i.e. more space between bean bacteroids). Critically, pea bacteroids, fix N2 at higher rates versus bean per unit bacteroid protein, as protein expression is skewed towards N2 fixation and TCA-cycle enzymes. Pea bacteroids infect 1.6 times the percentage of nodule volume of beans (i.e., 14.2% versus 9.1%). Overall, the increased packing density of pea bacteroids, as well as the bias of their proteome to nitrogenase, associated N2 fixation processes, and dicarboxylate metabolism, contributes to their greater symbiotic efficiency, which is likely driven by plant antimicrobial peptides.
Unlocking plant health survey data: An approach to quantify the sensitivity and specificity of visual inspections
Matt Combes, Nathan Brown, Robin N. Thompson, Alexander Mastin, Peter Crow, Stephen Parnell
Invasive plant pests and pathogens cause substantial environmental and economic damage. Visual inspection remains a central tenet of plant health surveys, but its sensitivity (probability of correctly identifying the presence of a pest) and specificity (probability of correctly identifying the absence of a pest) are not routinely quantified. As knowing sensitivity and specificity of visual inspection is critical for effective contingency planning and outbreak management, we address this deficiency using empirical data and statistical analyses. Twenty-three citizen scientist surveyors assessed up to 175 labelled oak trees for three symptoms of acute oak decline. The same trees were also assessed by an expert who has monitored these individual trees annually for over a decade. The sensitivity and specificity of surveyors was calculated using the expert data as the ‘gold-standard’ (i.e., assuming perfect sensitivity and specificity). The utility of an approach using Bayesian modelling to estimate the sensitivity and specificity of visual inspection in the absence of a rarely available ‘gold-standard’ dataset was then examined with simulated plant health survey datasets. There was large variation in sensitivity and specificity between surveyors and between different symptoms, although the sensitivity of detecting a symptom was positively related to the frequency of the symptom on a tree. By leveraging surveyor observations of two symptoms from a minimum of 80 trees on two sites, with reliable prior knowledge of sites with a higher (~0.6) and lower (~0.3) true disease prevalence we show that sensitivity and specificity can be estimated without ‘gold-standard’ data using Bayesian modelling. We highlight that sensitivity and specificity will depend on the symptoms of a pest or disease, the individual surveyor, and the survey protocol. This has consequences for how surveys are designed to detect and monitor outbreaks, as well as the interpretation of survey data that is used to inform outbreak management.
Updated Priorities for Cerebroprotection Trials
Sean Savitz, Edgar Samaniego, David Liebeskind, Johannes Boltze
A STAIR XIII workshop was held to discuss aspects of trials likely to have the greatest impact on detecting meaningful treatment effects of cerebroprotection in acute stroke. Intended goals for hyperacute protection should be focused on preserving penumbral tissue and delaying infarct core growth to augment the impact of reperfusion therapies. Infarct volume is a biologically and clinically meaningful surrogate imaging marker to assess the treatment effects of cerebroprotection. Lastly, clinical outcome measures for cerebroprotection should include domain-specific and patient-centered outcomes to detect clinically meaningful changes across multiple functional domains.
Perspectives from a Workshop: Intelligent Assessment in the age of Artificial Intelligence
Matt Bawn, Nigel Francis, Liz Alvey, Christopher Hassall, Andre Pires-daSilva, Pedro Barra, Denise Hough, Hannah Campbell, Matt Hardy, Juanvi Canet-Perez
The advent of Generative Artificial Intelligence (GenAI) is already impacting pedagogic strategies and assessment methodologies in higher education, particularly in the biological sciences which have traditionally relied heavily on written assessments. GenAI's rapid and plausible text generation capabilities challenge traditional written assessments and prompt a shift towards more authentic assessment types. This paper explores innovative applications of GenAI in biology education through case studies presented at a recent workshop. These case studies illustrate how GenAI has the potential to enhance academic activities, from developing learning resources to fostering student engagement through active learning strategies. The discussion highlights a shift from product-oriented assessments to process-oriented approaches that prioritize continuous interaction, iteration, and reflection among learners. Despite GenAI's reliance on pre-existing data raising concerns about originality and contextual accuracy, and its limitations in tasks requiring high creativity and deep understanding, it has the potential to enhance educational practices when applied with awareness of its constraints. The paper concludes with a balanced analysis of the transformative impact and inherent challenges of integrating GenAI into biology education, advocating for thoughtful implementation to ensure it augments rather than replaces traditional teaching methods.
Advances in Physiology Education- November 2025
PRC1-mediated H2A.Zub promotes gene expression by preventing H3.1K27me1 incorporation in Arabidopsis
Fernando Baile, Javier Antúnez-Sánchez, Jose Gutierrez-Marcos, Myriam Calonje
Background: PcG complexes are pivotal in orchestrating the transition from embryonic to vegetative development in plants. However, the mechanisms underlying the gene expression reprogramming that takes place during this developmental transition are still not fully understood. Several studies suggest that incorporating PcG modifications into distinct histone variants may play a key role in this process. However, while PRC2-mediated H3K27me3 is essential for gene repression, the timing of PRC2 action on canonical H3.1 or variant H3.3 remains unclear. Furthermore, the exact role of PRC1 in transcriptional regulation is still unresolved, partly owing to limited knowledge of the conditions under which this complex monoubiquitinates canonical H2A or H2A.Z variant.
Results: Here, we demonstrate that H2A.Z undergoes monoubiquitination during the seed-to-seedling transition. H2A.Zub facilitates the recruitment of PRC2 to mediate H3.3 trimethylation, repressing seed-specific genes; however, H2A.Zub also promotes the activation of vegetative-specific genes by preventing H3K27me1 incorporation into H3.1. Notably, the histone demethylase REF6 initiates this process by removing two methyl groups from stably repressed H3.1K27me3-marked genes, enabling the subsequent H2A.Zub incorporation. This result suggests that REF6 activity is a critical early step in PRC1-mediated transcriptional activation.
Conclusions: Our findings reveal the long-sought mechanism by which PRC1 participates in transcriptional activation. We demonstrate that PRC1-mediated H2A.Zub, acting as a “switcher”, plays a pivotal role in reprogramming active and repressed genes during the transition from embryonic to vegetative development. Moreover, our results provide new insights into the intricate relationship between histone modifications and histone variants in reprogramming and maintaining gene expression patterns.