Latest Publications
Drivers of epidemic dynamics in real time from daily digital COVID-19 measurements
Michelle Kendall, Luca Ferretti, Chris Wymant, Daphne Tsallis, James Petrie, Andrea di Francia, Franceso di Lauro, Lucie Abeler-Dorner, Harrison Manley, Jasmina Panovska-Griffiths, Alice Ledda, Xavier Didelot and Christophe Fraser
Understanding the drivers of respiratory pathogen spread is challenging, particularly in a timely manner during an ongoing epidemic. Here we present insights obtained using daily data from the NHS COVID-19 app for England and Wales and shared with health authorities in almost real time. Our indicator of the reproduction number R(t) was available days earlier than other estimates, with a novel capability to decompose R(t) into contact rates and probabilities of infection. When Omicron arrived, the main epidemic driver switched from contacts to transmissibility. We separate contacts and transmissions by day of exposure and setting, finding pronounced variability over days of the week and during Christmas holidays and events. As an example, during the Euro football tournament in 2021, days with England matches showed sharp spikes in exposures and transmissibility. Digital contact tracing technologies can help control epidemics not only by directly preventing transmissions but also by enabling rapid analysis at scale and with unprecedented resolution.
Membrane potential dynamics unveil the promise of Bioelectrical Antimicrobial Susceptibility Testing (BeAST) for anti-fungal screening
Tailise Carolina de Souza-Guerreiro, Letícia Huan Bacellar, Thyerre Santana da Costa, Conor LA Edwards, Ljubica Tasic & Munehiro Asally
Membrane potential is a useful marker for antimicrobial susceptibility testing (AST) due to the fundamental characteristic of vital cells. However, the difficulties associated with measuring the membrane potential in microbes restrict its broad application. In this study, we present Bioelectrical AST (BeAST) using the model fungus Saccharomyces cerevisiae . The results suggest that BeAST holds promise for screening anti-fungal compounds, offering a valuable approach to tackling antimicrobial resistance.
Mike Tildesley publications
When should lockdown be implemented? Devising cost-effective strategies for managing epidemics amid vaccine uncertainty
Doyle, Nathan, Cumming, Fergus, Thompson, Robin N. and Tildesley, Michael J.
We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV), and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period due to high mortality; therefore, the overall basic reproduction number of AHSV is similar to BTV. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreak, and could help guide policy makers seeking to mitigate the impact of climate change on disease control. PLoS Computational Biology. July 2024
Modelling the Influence of Climate and Vector Control Interventions on Arbovirus Transmission
We combine features of existing models to develop a novel model for vectorial capacity that considers both climate and vector control. This model considers how vector control tools affect vectors at each stage of their feeding cycle, and incorporates host availability and preference. Applying this model to arboviruses of veterinary importance in Europe, we show that African horse sickness virus (AHSV) has a higher peak predicted vectorial capacity than bluetongue virus (BTV), Schmallenberg virus (SBV), and epizootic haemorrhagic disease virus (EHDV). However, AHSV has a shorter average infectious period due to high mortality; therefore, the overall basic reproduction number of AHSV is similar to BTV. Overall, this model can be used to consider both climate and vector control interventions either currently utilised or for potential use in an outbreak, and could help guide policy makers seeking to mitigate the impact of climate change on disease control. Viruses. July 2024
Adenosine signalling to astrocytes coordinates brain metabolism and function
Shefeeq M. Theparambil, Olga Kopach, Alice Braga, Shereen Nizari, Patrick S. Hosford, Virag Sagi-Kiss, Anna Hadjihambi, Christos Konstantinou, Noemi Esteras, Ana Gutierrez Del Arroyo, Gareth L. Ackland, Anja G. Teschemacher, Nicholas Dale, Tobias Eckle, Petros Andrikopoulos, Dmitri A. Rusakov, Sergey Kasparov & Alexander V. Gourine
Brain computation performed by billions of nerve cells relies on a sufficient and uninterrupted nutrient and oxygen supply. Astrocytes, the ubiquitous glial neighbours of neurons, govern brain glucose uptake and metabolism, but the exact mechanisms of metabolic coupling between neurons and astrocytes that ensure on-demand support of neuronal energy needs are not fully understood. Here we show, using experimental in vitro and in vivo animal models, that neuronal activity-dependent metabolic activation of astrocytes is mediated by neuromodulator adenosine acting on astrocytic A2B receptors. The data identifies the adenosine A2B receptor as an astrocytic sensor of neuronal activity and show that cAMP signalling in astrocytes tunes brain energy metabolism to support its fundamental functions such as sleep and memory.
A Multipronged Bioengineering, Spectroscopic and Theoretical Approach in Unravelling the Excited-State Dynamics of the Archetype Mycosporine Amino Acid
Michael Hymas, Sopida Wongwas, Simin Roshan, Abigail L. Whittock, Christophe Corre, Reza Omidyan and Vasilios G. Stavros
Mycosporine glycine (MyG) was produced by the fermentation of a purposely engineered bacterial strain and isolated from this sustainable source. The ultrafast spectroscopy of MyG was then investigated in its native, zwitterionic form (MyGzwitter), via femtosecond transient electronic absorption spectroscopy. Complementary nonadiabatic (NAD) simulations suggest that, upon photoexcitation to the lowest excited singlet state (S1), MyGzwitter undergoes efficient nonradiative decay to repopulate the electronic ground state (S0). We propose an initial ultrafast ring-twisting mechanism toward an S1/S0 conical intersection, followed by internal conversion to S0 and subsequent vibrational cooling. This study illuminates the workings of the archetype mycosporine, providing photoprotection, in the UV–B range, to organisms such as corals, macroalgae, and cyanobacteria. This study also contributes to our growing understanding of the photoprotection mechanisms of life.
Within-Host Viral Growth and Immune Response Rates Predict Foot-and-Mouth Disease Virus Transmission Dynamics for African Buffalo
Joshua C. Macdonald, Hayriye Gulbudak, Brianna Beechler, Erin E. Gorsich, Simon Gubbins, Eva Pérez-Martin and Anna E. Jolles
We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. Our data reveals contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus’s relative basic reproductive number (ℛ0), suggesting that viral invasion potential may be predictable from within-host dynamics.