Latest Publications
Ancient genomes reveal insights into ritual life at Chichén Itzá
Rodrigo Barquera, Oana Del Castillo-Chávez, Kathrin Nägele, Patxi Pérez-Ramallo, Diana Iraíz Hernández-Zaragoza, András Szolek, Adam Benjamin Rohrlach, Pablo Librado, Ainash Childebayeva, Raffaela Angelina Bianco, Bridget S. Penman, Victor Acuña-Alonzo, Mary Lucas, Julio César Lara-Riegos, María Ermila Moo-Mezeta, Julio César Torres-Romero, Patrick Roberts, Oliver Kohlbacher, Christina Warinner & Johannes Krause
Here we present genome-wide data obtained from 64 subadult individuals dating to around AD 500-900 that were found in a subterranean mass burial near the Sacred Cenote (sinkhole) in the ceremonial centre of Chichén Itzá. Genetic analyses showed that all analysed individuals were male and several individuals were closely related, including two pairs of monozygotic twins. Twins feature prominently in Mayan and broader Mesoamerican mythology, where they embody qualities of duality among deities and heroes, but until now they had not been identified in ancient Mayan mortuary contexts. Genetic comparison to present-day people in the region shows genetic continuity with the ancient inhabitants of Chichén Itzá, except at certain genetic loci related to human immunity, including the human leukocyte antigen complex, suggesting signals of adaptation due to infectious diseases introduced to the region during the colonial period. Nature. June 2024
A climatic suitability indicator to support Leishmania infantum surveillance in Europe : a modelling study
Carvalho, Bruno M., Maia, Carla, Courtenay, Orin, Llabrés-Brustenga, Alba, Lotto Batista, Martín, Moirano, Giovenale, van Daalen, Kim R., Semenza, Jan C. and Lowe, Rachel
Leishmaniases are neglected diseases transmitted by sand flies. The aim of this modelling study was to develop an indicator that tracks climatic suitability for Leishmania infantum transmission in Europe at the subnational level. Historical records of sand fly vectors, human leishmaniasis, bioclimatic indicators, and environmental variables were integrated in a machine learning framework (XGBoost) to predict suitability in two past periods (2001–2010 and 2011–2020. This study demonstrates how key epidemiological data can be combined with open-source climatic and environmental information to develop an indicator that effectively tracks spatiotemporal changes in climatic suitability and disease risk. The positive association between the model predictions and human disease incidence demonstrates that this indicator could help target leishmaniasis surveillance to transmission hotspots.
Molecular motor tug-of-war regulates elongasome cell wall synthesis dynamics in Bacillus subtilis
Stuart Middlemiss, Matthieu Blandenet, David M. Roberts, Andrew McMahon, James Grimshaw, Joshua M. Edwards, Zikai Sun, Kevin D. Whitley, Thierry Blu, Henrik Strahl & Seamus Holden
Most rod-shaped bacteria elongate by inserting new cell wall material into the inner surface of the cell sidewall. This is performed by class A penicillin binding proteins (PBPs) and a highly conserved protein complex, the elongasome, which moves processively around the cell circumference and inserts long glycan strands that act as barrel-hoop-like reinforcing structures, thereby giving rise to a rod-shaped cell. However, it remains unclear how elongasome synthesis dynamics and termination events are regulated to determine the length of these critical cell-reinforcing structures. To address this, we developed a method to track individual elongasome complexes around the entire circumference of Bacillus subtilis cells for minutes-long periods using single-molecule fluorescence microscopy. Our results demonstrate that molecular motor tug-of-war is a key regulator of elongasome dynamics in B. subtilis, which likely also regulates the cell shape via modulation of elongasome processivity.
Phenotypic and genotypic characterization of fifty strains of Beauveria spp. (Ascomycota, Cordycipitaceae) fungal entomopathogens from diverse geographic origins against the diamondback moth, Plutella xylostella (Lepidoptera: Plutellidae)
Laura Reyes-Haro, Gillian Prince, Rommel Santiago Granja-Travez, David Chandler
The diamondback moth (DBM) (Plutella xylostella) causes large losses to global crop production. Conventional insecticides are losing effectiveness due to resistance. Consequently, there is a growing interest in sustainable control methods like entomopathogenic fungi (EPF) in Integrated Pest Management. However, the field efficacy of fungi varies due to environmental influences. In this study, a group of 50 Beauveria strains sourced from different locations were characterized by genotype and phenotype with respect to their conidial production, temperature and UV-B radiation tolerance, and virulence against DBM. Survival under environmental conditions is crucial for EPF-based commercial products against DBM. Results suggest strain tolerance to environmental stressors is more tied to specific micro-climatic factors than geographical origin. Each strain exhibited unique characteristics; for example, the most virulent strain (#29) was highly UV-sensitive. Therefore, characterizing diverse strains provides essential genotypic and phenotypic insights, which are fundamental for understanding their role as biocontrol agents while facilitating efficient biopesticide product development and uptake
Structures of wild-type and a constitutively closed mutant of connexin26 shed light on channel regulation by CO2
Deborah H. Brotherton, Sarbjit Nijjar, Christos G. Savva, Nicholas Dale, Alexander D. Cameron
Connexins allow intercellular communication by forming gap junction channels (GJCs) between juxtaposed cells. Connexin26 (Cx26) can be regulated directly by CO2. This is proposed to be mediated through carbamylation of K125. We show that mutating K125 to glutamate, mimicking the negative charge of carbamylation, causes Cx26 GJCs to be constitutively closed. Through cryo-EM we observe that the K125E mutation pushes a conformational equilibrium towards the channel having a constricted pore entrance, similar to effects seen on raising the partial pressure of CO2. In previous structures of connexins, the cytoplasmic loop, important in regulation and where K125 is located, is disordered. Through further cryo-EM studies we trap distinct states of Cx26 and observe density for the cytoplasmic loop. The interplay between the position of this loop, the conformations of the transmembrane helices and the position of the N-terminal helix, which controls the aperture to the pore, provides a mechanism for regulation.
Combining models to generate consensus medium-term projections of hospital admissions, occupancy and deaths relating to COVID-19 in England
Harrison Manley,Thomas Bayley,Gabriel Danelian, Lucy Burton, Thomas Finnie, Andre Charlett, Nicholas A. Watkins, Paul Birrell, Daniela De Angelis, Matt Keeling, Sebastian Funk, Graham Medley, Lorenzo Pellis, Marc Baguelin, Graeme J. Ackland, Johanna Hutchinson, Steven Riley and Jasmina Panovska-Griffiths
Mathematical modelling has played an important role in offering informed advice during the COVID-19 pandemic. In England, a cross government and academia collaboration generated medium-term projections (MTPs) of possible epidemic trajectories over the future 4–6 weeks from a collection of epidemiological models. In this article, we outline this collaborative modelling approach and evaluate the accuracy of the combined and individual model projections against the data over the period Learning from our experience of ensemble modelling during the COVID-19 epidemic, our findings highlight the importance of developing cross-institutional multi-model infectious disease hubs for future outbreak control.