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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Congratulations to Dr Cerys Currie, winner of the Science Category in the Women of the Future Awards. She received her award at a ceremony in London on Wednesday 9 November. Two members of Warwick Medical School were shortlisted this year. Alongside Cerys, Postdoctoral Research Fellow and final year medical student Ramat Ayoola, was nominated in the Community Spirit category.

Association between fetal abdominal growth trajectories, maternal metabolite signatures early in pregnancy, and childhood growth and adiposity: prospective observational multinational INTERBIO-21st fetal study

New study from the Bowman Lab published in eLife defines a novel nuclear translocation pathway involving the specific import receptor Importin-5 and the histone chaperone NASP that specialise in ferrying monomeric histones to the nucleus.

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Nanoparticles have found widespread use in diagnostics and have been suggested for e.g. drug delivery. Chemists can now fine tune the nanoparticle surface to e.g target cell types. However, what a cell 'sees' is not what is made by the chemists, but rather a complex mixture of proteins which ‘foul’ the surface, recruited from the blood, termed the protein corona. There has been extensive research into the proteins which make up the corona, but the glycans on these proteins have received less attention. This is a major problem, as > 50 % of our proteome is glycosylated, and hence investigating a nanoparticle’s protein corona, without considering the glycans, does not give an accurate picture.

In our latest work, we investigate the impact of the glycoprotein corona on how polymer-coated nanoparticles bind lectins. We show that serum proteins bring significant sialic acids to the particle surface. The impact of this, is that the particles can bind additional lectins (which were not intended) as well as those which are intended. Finally, we show that 'blocking' the surface does reduce the amount of protein, but sufficient glycans remain to cause off-target binding. These results will help guide the next generation of nanoparticle sensing and delivery agents.
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The use of nanoparticles as drug delivery vehicles is well established. Numerous studies have investigated the impact of size, shape, charge, and surface functionality of nanoparticles on mammalian cellular uptake. Rigidity, however, has been studied to a far lesser extent, and its effects are still unclear. Here, in a collaboration between the Chemistry and BMS, this is systematically explored.

Three different polymeric core rigidities were tested: hard, medium and soft using two 50 and 100 nm diameter particles. Cellular uptake studies indicated that 100nm softer particles are taken up faster and 3-fold more into mammalian cells compared to harder nanoparticles, probably via major differences in the cellular uptake pathways. However, 50 nm derivatives did not show any appreciable differences in uptake efficiency suggesting that rigidity as a parameter for nanomaterials in the biological regime might be size dependent.

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In a recent study published in Cell Reports, teams from University College London and Warwick Medical School describe how protein fusion of two epigenetic modulators, JAZF1 and SUZ12, causes oncogenesis in human endometrial stromal cells by disrupting the composition of the polycomb repressive complex 2 (PRC2), resulting in aberrant histone modification, gene expression and cell differentiation (decidualization). The results reveal how dysregulation of PRC2 drives the emergence of low-grade endometrial stromal sarcomas in the womb, which provide opportunities to improve the treatment of this disease.

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