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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3-D tissue models (such as spheroids and organoids) better predict physiological responses than 2D monolayers and may play a role in reducing animal usage, particularly in toxicology. Spheroids are more challenging, however, to work with than cell monolayers and hence there is a barrier to their use. Spheroids can also not (always) be easily cryopreserved and hence buying them ‘off the shelf’ and ‘ready to use’ is not common or is expensive. The GibsonGroup, working with Cryologyx, have show in this latest work that their macromolecular cryoprotectants can protect live cell spheroids during cryopreservation allowing the recovery of viable spheroids direct from the freezer.
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Sleep and circadian rhythm disruption (SCRD), as encountered during shift work, increases the risk of respiratory viral infection including SARS-CoV-2. However, the mechanism(s) underpinning higher rates of respiratory viral infection following SCRD remain poorly characterised. To address this, we investigated the effects of acute sleep deprivation on the mouse lung transcriptome. Here we show that sleep deprivation profoundly alters the transcriptional landscape of the lung, causing the suppression of both innate and adaptive immune systems, disrupting the circadian clock, and activating genes implicated in SARS-CoV-2 replication, thereby generating a lung environment that promotes viral infection and associated disease pathogenesis. Our study provides a mechanistic explanation of how SCRD increases the risk of respiratory viral infections including SARS-CoV-2 and highlights therapeutic avenues for the prevention and treatment of COVID-19.
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Nuria Ferrandiz and colleagues in the Royle lab published a paper in J Cell Biol this summer on mitotic chromosome "ensheathing" by endomembranes. This paper was selected by the JCB as one of the 10 best papers of 2022. JCB have put together a supplement containing summaries of all ten papers with photos of the authors.
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The GibsonGroup have a large interest in mimicking the function of ice binding proteins (IBPs) using polymers, which have huge biotechnological, biomedical and industrial potential. The team have previously made progress in mimicking ‘antifreeze’ proteins, but the search for a polymer which can nucleate ice has been elusive. Ice nucleating proteins (INPs) are very large, and truncated versions are far less active, and the native proteins are immobilised in membranes making their study challenging. In this latest work, the team report (what they believe) is the first polymeric ice nucleator. To achieve this they took an ice binding polymer and used synthetic polymer chemistry to make a ‘brush shaped’ polymer to introduce rigidity and very high molecular weight (100’s of kDAs). This new tool is the first synthetically accessible ‘organic’ probe for ice nucleation.
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