Dr John James' lab have used a cellular reconstitution of preTCR function to investigate the trafficking dynamics of this developmentally important immune receptor, work which has just been published in the Journal of Cell Biology.

Expression of the pre-T cell receptor (preTCR) is an important checkpoint during the development of T cells, an essential cell type of our adaptive immune system. The preTCR complex is only transiently expressed and rapidly internalized in developing T cells and is thought to signal in a ligand-independent manner. However, identifying a mechanistic basis for these unique features of the preTCR compared with the final TCR complex has been confounded by the concomitant signaling that is normally present. Thus, we have reconstituted preTCR expression in non-immune cells to uncouple receptor trafficking dynamics from its associated signaling. We find that all the defining features of the preTCR are intrinsic properties of the receptor itself, driven by exposure of an extracellular hydrophobic region, and are not the consequence of receptor activation. Finally, we show that transitory preTCR cell surface expression can sustain tonic signaling in the absence of ligand binding, suggesting how the preTCR can nonetheless drive αβTCR lineage commitment.

Read the paper here.

Advanced cell-based therapies are often delivered to the patient frozen. Hence, any technology which increases the number of recovered, viable, cells post-thaw may improve clinical outcomes or allow more treatments per donation. The GibsonGroup have previously shown strategies to protect cells during freezing. In this latest work, in collaboration with Cytiva, the team show that incubating a model t-cell line with proline before cryopreservation leads to increased post-thaw cell yields. All proline is removed before cryopreservation so the actual freezing and thawing processes are unchanged. It was shown that proline limits cell proliferation, which might be contributing to its mode of action similar to ‘metabolic pre-conditioning’ which has been shown before.

Read the paper here.

Glycans (sugars) dictate cell-cell communication, are sites for pathogen invasion and are a key part of our immune systems. Current synthetic platforms to display glycans to investigate their biology almost always are imperfect, with heterogeneity in terms of number of glycans and the synthesis is not reproducible batch to batch. The Gibson and Ward (chemistry) groups have collaborated on a Leverhulme-Trust funded project to create ‘programmable’ glyco-clusters - before entering the lab, this method enables a research to know exactly how many glycans and their 3-D location are present on a material, and gives zero heterogeneity. This is achieved using metal co-ordination cages - 3D structures formed by spontaneous self-assembly. The team used these with model glycan-binding proteins to identify key interactions which would not be possible with traditional materials. The team are now using this to interrogate a range of targets including toxins, for diagnostics.

Read the paper here.

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

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.

Read the paper hereLink opens in a new window.