A sleeping sickness parasite is the first pathogen to have its proteins located and mapped within its cells. These parasites have made large areas of Africa unsuitable for livestock production, costing rural farmers up to £3.7bn each year.

For the first time ever, scientists have developed a detailed “protein atlas” of a pathogen – a kind of biological map that locates proteins in cells. They conducted the research on Trypanosoma brucei (T. brucei), helping to understand where proteins are within its cells, providing functional insights that may ultimately help treat parasite infections.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe coronavirus disease 2019 (COVID-19) in a small proportion of infected individuals. The immune system plays an important role in the defence against SARS-CoV-2, but our understanding of the cellular immune parameters that contribute to severe COVID-19 disease is incomplete. Here, we show that populations of human effector γδ T cells are associated with acute COVID-19 in unvaccinated patients. We found that circulating killer-type γδ T cells were enriched in COVID-19 patients with acute disease. Surprisingly, SARS-CoV-2 infection did not alter the γδ T cell receptor repertoire, like in other viral infections. Thus, our work demonstrates a link between the systemic activation of effector populations of γδ T cells and acute COVID-19 in unvaccinated individuals.

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Congratulations to Professor Andrew McAinsh, Pro Dean for Research at WMS, who has just been awarded a Wellcome Discovery Award and Research Grant of over £2.5M. The research programme ‘Kinetochore self-correction mechanisms underlying faithful chromosome segregation in humans’ will run for eight years. Read the full news item here.

The GibsonGroup, in collaboration RCSI (Dublin), have demonstrated that polyproline is a structurally simple mimic of antifreeze glycoproteins. The GibsonGroup have a large interest in developing materials which can control ice growth/formation, and their application in biotechnology. This is inspired by antifreeze proteins, which can be challenging to obtain and are not suitable for scale up. The antifreeze glycoproteins are known to adopt a PPII helix in solution, and in this latest work the team show that polyproline itself is sufficient for ice binding and inhibiting ice growth, when it has sufficiently high molecular weight. This is significantly simpler than using a glycoprotein and supports growing evidence that the ‘hydrophobic’ face of AFGPs binds the ice, rather than the glycans, and that hydrogen bonding to the ice is not always essential for activity. Finally, this also shows that bio-renewable resources can be used to obtain ice growth inhibitors which themselves could be biodegradable.

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Liquid biopsies of circulating tumor cells (CTCs) have the potential to transform cancer management through non-invasive, real-time feedback on patient conditions. However, immunoaffinity-based liquid biopsies typically suffer from low throughput, relative complexity, and postprocessing limitations. Here, we addressed these issues simultaneously by decoupling and independently optimizing the nano-, micro-, and macro-scales of an enrichment device that is simple to fabricate and operate. Unlike other affinity-based devices, our scalable mesh approach enables optimum capture conditions at any flow rate. The device detected CTCs under experimental conditions and in the blood of cancer patients where it also allowed for postprocessing and, thus, identification of clinically relevant biomarkers such as HER2, but also has the potential to predict patient response to therapies such as immune checkpoint inhibition therapy in the future. This suggests that our approach can overcome major limitations associated with affinity-based liquid biopsies and help improve cancer management.

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Bacillus cereus G9241 was isolated from a Louisiana welder suffering from an anthrax-like infection. The organism carries two transcriptional regulators that have previously been proposed to be incompatible with each other in Bacillus anthracis: the pleiotropic transcriptional regulator PlcR found in most members of the Bacillus cereus group but truncated in all B. anthracis isolates, and the anthrax toxin regulator AtxA found in all B. anthracis strains and a few B. cereus sensu stricto strains. Here we report cytotoxic and haemolytic activity of cell free B. cereus G9241 culture supernatants cultured at 25 °C to various eukaryotic cells. However, this is not observed at the mammalian infection relevant temperature 37 °C, behaving much like the supernatants generated by B. anthracis. Using a combination of genetic and proteomic approaches to understand this unique phenotype, we identified several PlcR-regulated toxins to be secreted highly at 25 °C compared to 37 °C. Furthermore, results suggest that differential expression of the protease involved in processing the PlcR quorum sensing activator molecule PapR appears to be the limiting step for the production of PlcR-regulated toxins at 37 °C, giving rise to the temperature-dependent haemolytic and cytotoxic activity of the culture supernatants. This study provides an insight on how B. cereus G9241 is able to ‘switch’ between B. cereus and B. anthracis–like phenotypes in a temperature-dependent manner, potentially accommodating the activities of both PlcR and AtxA.

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Bacillus cereus G9241 was isolated from a welder who survived a pulmonary anthrax-like disease. Strain G9241 carries two virulence plasmids, pBCX01 and pBC210, as well as an extrachromosomal prophage, pBFH_1. pBCX01 has 99.6% sequence identity to pXO1 carried by Bacillus anthracis and encodes the tripartite anthrax toxin genes and atxA, a mammalian virulence transcriptional regulator. This work looks at how the presence of pBCX01 and temperature may affect the lifestyle of B. cereus G9241 using a transcriptomic analysis and by studying spore formation, an important part of the B. anthracis lifecycle. . Here we report that pBCX01 has a stronger effect on gene transcription at the mammalian infection relevant temperature of 37˚C in comparison to 25˚C. At 37˚C, the presence of pBCX01 appears to have a negative effect on genes involved in cell metabolism, including biosynthesis of amino acids, whilst positively affecting the transcription of many transmembrane proteins. The figure below shows the first image of the anthrax G9241 cross-over strain linear chromosome bacteriophage (unusual in bacteriophage itself).

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We reveal that the developing Drosophila nerve cord has a distinctive architectural structure, which is driven by JNK signalling.
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A collaborative study by the Thompson group with Dr Robin Thompson's (Mathematics Institute, University of Warwick) and Dr Uri Obolski's (Tel Aviv University) groups. The study examines the impact of prior immunity conferred by SARS-CoV-2 or seasonal coronavirus infection on the emergence of new variants using mathematical modelling . We find that, if cross-reactive immunity is complete (i.e. someone infected by the previously circulating virus is not susceptible to the novel variant), the novel variant must be more transmissible than the previous virus to invade the population. However, in a more realistic scenario in which cross-reactive immunity is partial, we show that it is possible for novel variants to invade, even if they are less transmissible than previously circulating viruses. Finally, we find that if previous infection with the antigenically related virus assists the establishment of infection with the novel variant, as has been proposed following some experimental studies, then even variants with very limited transmissibility are able to invade the host population.

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The GibsonGroup have a programme of research to investigate how glycans (sugars) can be used in biosensing or diagnosis of disease. In the latest publication from the team, they show how otherwise identifical proteins with different glycosylation patterns can be identified and discriminated between. This is achieved by using antibodies immobilised on biolayer interferometry sensors which can first target all glycoforms (and hence are are not specific). In a second step, gold nanoparticles labelled with lectins (carbohydrate binding proteins) are used to identify which glycoform is present, and due to the large mass of the gold particles leads to signal enhancement. This is demonstrated for prostate specific antigen - a key biomarker for prostate diseases including cancer. It is known that the glycosylation pattern, not just protein concentration, is a hallmark of disease state but current techniques do not distinguish glycoforms. The method shown her can be automated and takes < 90 minutes to complete in this proof of concept study.
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