Spheroids (and organoids) can reproduce key aspects of human biological responses, and since the FDA simplification act it is possible (in some cases) to bypass animal testing in the development of new drugs where quality tissue models exist. However, these are not accessible ‘off the shelf’ so are not widely used, with monolayer culture then animal studies common. The GibsonGroup working with the WhaleGroup have recently shown how controlled nucleation (making ice form) can actually improve cryopreservation outcomes by reducing intracellular ice formation. In this latest work they combine nucleation with proline-pre conditioning which ‘prepares’ cells for cryopreservation. This shows how joined-up thinking of cryopreservation as a biochemical and biophysical problem can make a major impact on cell-storage platform technologies.

Read the paper here.

Bacteriophage (phage) are present wherever their bacteria hosts are. Phage have huge biotechnological potential, but lytic phages can also cause complete loss of bacterial cultures. For example in the food industry, or in every research laboratory, where rigorous sterile handing is the primary containment strategy. For industrial biotechnology using microorganisms to enable sustainable of chemicals, materials and drugs, phage infection must be addressed. In our latest (patent pending) work, in collaboration with the SagonaLab at Warwick, and Cytiva, we discovered that a simple polymer can prevent phage infection of bacteria when applied to the growth media. This process is simple, requires no change to working practises and prevents phage infections. We are still investigating the mechanistic aspects, but this is virustatic (inhibitory) rather than virucidal.

Read the press release here.
Read the paper here.

The biology of a cell is the sum of many highly dynamic processes, each orchestrated by a plethora of proteins and other molecules.

Microscopy is an invaluable approach to spatially and temporally dissect the molecular details of these processes. Hundreds of genetically encoded imaging tools have been developed that allow cell scientists to determine the function of a protein of interest in the context of these dynamic processes. Broadly, these tools fall into three strategies: observation, inhibition and activation. Using examples for each strategy, in this Cell Science at a Glance and the accompanying poster, we provide a guide to using these tools to dissect protein function in a given cellular process. Our focus here is on tools that allow rapid modification of proteins of interest and how observing the resulting changes in cell states is key to unlocking dynamic cell processes. The aim is to inspire the reader's next set of imaging experiments.

Read the paper here.

Dr Timothy Saunders and team have been awarded almost £300,000 by the British Heart foundation to study Fruit Fly Hearts!

Read more here:
Fruit fly helps Warwick scientists understand human heart development - BHF

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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Access the resource here and read the full paper here.

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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