Latest Publications
LipIDens: Simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins.
T. Bertie Ansell, Wanling Song, Claire E. Coupland, Loic Carrique, Robin A. Corey, Anna L. Duncan, C. Keith Cassidy, Maxwell M. G. Geurts, Tim Rasmussen, Andrew B. Ward, Christian Siebold, Phillip J. Stansfeld, Mark S. P. Sansom
Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures.
Modelling seasonality of Lassa fever incidences and vector dynamics in Nigeria
McKendrick, James, Tennant, Warren S. D. and Tildesley, Michael J.
Lassa fever (Lf) is a viral haemorrhagic disease endemic to West Africa and is caused by the Lassa mammarenavirus. The rodent Mastomys natalensis serves as the primary reservoir and its ecology and behaviour have been linked to the distinct spatial and temporal patterns in the incidence of Lf. While previous research has modelled the case seasonality within Nigeria, this did not capture the seasonal variation in the reproduction of the zoonotic reservoir and its effect on case numbers. To this end, we introduce an approximate Bayesian computation scheme to fit our model to the case data from 2018–2020 supplied by the NCDC. In this study we used a periodically forced seasonal nonautonomous system of ordinary differential equations as a vector model to demonstrate that the population dynamics of the rodent reservoir may be responsible for the spikes in the number of observed cases in humans.
George Bassel publications
A quantitative morphospace of multicellular organ design in the plant Arabidopsis
Salva Duran-Nebreda, Matthew D.B. Jackson, George W. Bassel
The investigation of cellular organization can provide insight into organ function following structure-function relationships. Here, we investigate the extent to which properties in cellular organization can arise ‘‘for free’’ as an emergent property of embedding cells in space versus those that are actively generated by patterning processes. A 3D cellular-resolution digital tissue atlas for the model plant species Arabidopsis was generated, and the extent to which the organs in this organism conform to the default configurations was established through statistical comparisons with digital tissue models. This work establishes a quantitative morphospace to understand the principles of organ construction and its diversity within a single organism.
Current Biology. November 2023
Toward uncovering an operating system in plant organs
Gwendolyn V Davis, Tatiana de Souza Moraes, Swanand Khanapurkar, Hannah Dromiack, Zaki Ahmad, Emmanuelle M Bayer, Rishikesh P Bhalerao, Sara I Walker, George W Bassel
Molecular motifs can explain information processing within single cells, while how assemblies of cells collectively achieve this remains less well understood. Plant fitness and survival depend upon robust and accurate decision-making in their decentralised multicellular organ systems. Mobile agents, including hormones, metabolites, and RNAs, have a central role in coordinating multicellular collective decision-making, yet mechanisms describing how cell-cell communication scales to organ-level transitions is poorly understood. Here, we explore how unified outputs may emerge in plant organs by distributed information processing across different scales and using different modalities. Mathematical and computational representations of these events are also explored toward understanding how these events take place and are leveraged to manipulate plant development in response to the environment.
Innate Sleep Apnea in Spontaneously Hypertensive Rats Is Associated With Microvascular Rarefaction and Neuronal Loss in the preBötzinger Complex
Reno Roberts, Robert T.R. Huckstepp
Sleep apnea (SA) is a major threat to physical health and carries a significant economic burden. These impacts are worsened by its interaction with, and induction of, its comorbidities. SA holds a bidirectional relationship with hypertension, which drives atherosclerosis/arteriolosclerosis, ultimately culminating in vascular dementia. To enable a better understanding of these sequelae of events, we investigated innate SA and its effects on cognition in adult-aged spontaneously hypertensive rats, which have a range of cardiovascular disorders. Spontaneously hypertensive rats displayed a higher degree of sleep-disordered breathing, which emanates from poor vascular health leading to a loss of preBötzinger Complex neurons. These rats also display small vessel white matter disease, a form of vascular dementia, which may be exacerbated by the SA-induced neuroinflammation in the hippocampus to worsen the related deficits in both long- and short-term memories.
The effect of organic matter amendments on soil surface stability in conventionally cultivated arable fields
Jacqueline L. Stroud, Simon J. Kemp, Craig J. Sturrock
In this study, new and traditional organic wastes (green waste compost, farmyard manure (FYM), anaerobic digestate or straw) were ploughed into an arable field experiment at a range of rates (1–3 t C ha−1) and under spring and winter cropping rotations for 5 years. The stability of the soil surface structure (<5 cm) was assessed in Years 3, 4 and 5 to guide the use of organic wastes in arable field management. In conclusion, to achieve a stable soil surface structure, a 150% improvement in aggregate stability would be needed here and ploughing in organic wastes was not a successful management approach on these arable field experiments.
A smooth tubercle bacillus from Ethiopia phylogenetically close to the Mycobacterium tuberculosis complex.
Yenew, B., et al. (incl. Didelot, X)
The Mycobacterium tuberculosis complex (MTBC) includes several human- and animal-adapted pathogens. It is thought to have originated in East Africa from a recombinogenic Mycobacterium canettii-like ancestral pool. Here, we describe the discovery of a clinical tuberculosis strain isolated in Ethiopia that shares archetypal phenotypic and genomic features of M. canettii strains, but represents a phylogenetic branch much closer to the MTBC clade than to the M. canettii strains. Analysis of genomic traces of horizontal gene transfer in this isolate and previously identified M. canettii strains indicates a persistent albeit decreased recombinogenic lifestyle near the emergence of the MTBC. Our findings support that the MTBC emergence from its putative free-living M. canettii-like progenitor is evolutionarily very recent, and suggest the existence of a continuum of further extant derivatives from ancestral stages, close to the root of the MTBC, along the Great Rift Valley.