Latest Publications
A Pan Plasmodium lateral flow recombinase polymerase amplification assay for monitoring malaria parasites in vectors and human populations
Matthew Higgins, Mojca Kristan, Emma L. Collins, Louisa A. Messenger, Jamille G. Dombrowski, Leen N. Vanheer, Debbie Nolder, Christopher J. Drakeley, William Stone, Almahamoudou Mahamar, Teun Bousema, Michael Delves, Janvier Bandibabone, S茅v茅rin N鈥橠o, Chimanuka Bantuzeko, Bertin Zawadi, Thomas Walker, Colin J. Sutherland, Claudio R. F. Marinho, Mary M. Cameron, Taane G. Clark & Susana Campino
Malaria caused by neglected Plasmodium parasites is often underestimated due to the lack of rapid diagnostic tools that can accurately detect these species. Here, we present a Pan Plasmodium recombinase polymerase amplification lateral flow (RPA–LF) assay, capable of detecting all six human infecting Plasmodium species in low resource settings.. When combined with crude nucleic acid extraction, the assay can serve as a point-of-need tool for molecular xenomonitoring. This utility was demonstrated by screening laboratory-reared Anopheles stephensi mosquitoes fed with Plasmodium-infected blood, as well as field samples of An. funestus s.l. and An. gambiae s.l. collected from central Africa. Overall, our proof-of-concept Pan Plasmodium diagnostic tool has the potential to be applied for clinical and xenomonitoring field surveillance, and after further evaluation, could become an essential tool to assist malaria control and elimination.
Hendrik Schafer publications-
Overview of the MOSAiC expedition: Ecosystem
The international and interdisciplinary sea-ice drift expedition 鈥淭he Multidisciplinary drifting Observatory for the Study of Arctic Climate鈥� (MOSAiC) was conducted from October 2019 to September 2020. The aim of MOSAiC was to study the interconnected physical, chemical, and biological characteristics and processes from the atmosphere to the deep sea of the central Arctic system. The ecosystem team addressed current knowledge gaps and explored unknown biological properties over a complete seasonal cycle focusing on three major research areas: biodiversity, biogeochemical cycles, and linkages to the environment. This article provides a detailed overview of the sampling approaches used to address the three main science objectives. It highlights the core sampling program and provides examples of habitat- or process-specific sampling. The initial results presented include high biological activities in wintertime and the discovery of biological hotspots in underexplored habitats. The unique interconnectivity of the coordinated sampling efforts also revealed insights into cross-disciplinary interactions like the impact of biota on Arctic cloud formation. This overview further presents both lessons learned from conducting such a demanding field campaign and an outlook on spin-off projects to be conducted over the next years.
Microbial assimilatory sulfate reduction-mediated H2S: an overlooked role in Crohn's disease development
H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. The study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD.
Modelling bluetongue and African horse sickness vector (Culicoides spp.) distribution in the Western Cape in South Africa using random forest machine learning
de Klerk, Joanna N., Tildesley, Michael J., Labuschagne, Karien and Gorsich, Erin E
Culicoides biting midges exhibit a global spatial distribution and are the main vectors of several viruses of veterinary importance, including bluetongue (BT) and African horse sickness (AHS). The aim of this study was to model distributions for two primary vectors for BT and AHS (Culicoides imicola and Culicoides bolitinos) using random forest (RF) machine learning and explore the relative importance of environmental and anthropological factors in a region of South Africa with frequent AHS and BT outbreaks. This study yielded novel insight into the spatial abundance and drivers of abundance of competent vectors of BT and AHS. It also provided valuable data to inform mathematical models exploring disease outbreaks so that Culicoides-transmitted diseases in South Africa can be further analysed.
Self-organization of mortal filaments and its role in bacterial division ring formation
Christian Vanhille-Campos, Kevin D. Whitley, Philipp Radler, Martin Loose, Seamus Holden & An膽ela 艩ari膰
Filaments in the cell commonly treadmill. Driven by energy consumption, they grow on one end while shrinking on the other, causing filaments to appear motile even though individual proteins remain static. This process is characteristic of cytoskeletal filaments and leads to collective filament self-organization. Here we show that treadmilling drives filament nematic ordering by dissolving misaligned filaments. Taking the bacterial FtsZ protein involved in cell division as an example, we show that this mechanism aligns FtsZ filaments in vitro and drives the organization of the division ring in living Bacillus subtilis cells. We find that ordering via local dissolution also allows the system to quickly respond to chemical and geometrical biases in the cell, enabling us to quantitatively explain the ring formation dynamics in vivo. Beyond FtsZ and other cytoskeletal filaments, our study identifies a mechanism for self-organization via constant birth and death of energy-consuming filaments.
A neuronal circuit driven by GLP-1 in the olfactory bulb regulates insulin secretion
Mireia Montaner, Jessica Denom, Vincent Simon, Wanqing Jiang, Marie K. Holt, Daniel I. Brierley, Claude Rouch, Ewout Foppen, Nadim Kassis, David Jarriault, Dawood Khan, Louise Eygret, Francois Mifsud, David J. Hodson, Johannes Broichhagen, Lukas Van Oudenhove, Xavier Fioramonti, Victor Gault, Daniela Cota, Frank Reimann, Fiona M. Gribble, Stephanie Migrenne-Li, Stefan Trapp, Hirac Gurden & Christophe Magnan
Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an 伪2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.
Acidic polymers reversibly deactivate phages due to pH changes
Huba L. Marton, Antonia P. Sagona, Peter Kilbride and Matthew I. Gibson
Poly(carboxylic acids) have been reported to inhibit phages鈥� ability to infect their bacterial hosts and hence offer an exciting route to discover additives to prevent infection. Here, we report the role of pH in inactivating phages to determine if the polymers are unique or simply acidic. It is shown that lower pH (= 3) triggered by either acidic polymers or similar changes in pH using HCl lead to inhibition. There is no inhibitory activity at higher pHs (in growth media). It is also shown that poly(acrylic acid) leads to reversible deactivation of phage, but when the pH is adjusted using HCl alone the phage is irreversibly deactivated. Further experiments using metal binders ruled out ion depletion as the mode of action. These results show that polymeric phage inhibitors may work by unique mechanisms of action and that pH alone cannot explain the observed effects whilst also placing constraints on the practical utility of poly(acrylic acid).