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Professor Robert Cross awarded Biochemical Society Award for Sustained Excellence 2025

Professor Robert Cross, Warwick Medical School has been awarded the Biochemical Society Award for Sustained Excellence 2025.

The work and contribution of fifteen eminent bioscientists, outstanding educators and exceptional early career researchers has been acknowledged in the annual Biochemical Society Awards following a record year of nominations - Find out more and read the full article here

Thu 04 Apr 2024, 10:56 | Tags: news BMS

Long-range formation of the Bicoid gradient requires multiple dynamic modes that spatially vary across the embryo

Morphogen gradients provide essential positional information to gene networks through their spatially heterogeneous distribution, yet how they form is still hotly contested, with multiple models proposed for different systems. Here, we focus on the transcription factor Bicoid (Bcd), a morphogen that forms an exponential gradient across the anterior-posterior (AP) axis of the early Drosophila embryo. Using fluorescence correlation spectroscopy we find there are spatial differences in Bcd diffusivity along the AP axis, with Bcd diffusing more rapidly in the posterior. We establish that such spatially varying differences in Bcd dynamics are sufficient to explain how Bcd can have a steep exponential gradient in the anterior half of the embryo and yet still have an observable fraction of Bcd near the posterior pole. In the nucleus, we demonstrate that Bcd dynamics are impacted by binding to DNA. Addition of the Bcd homeodomain to eGFP::NLS qualitatively replicates the Bcd concentration profile, suggesting this domain regulates Bcd dynamics. Our results reveal how a long-range gradient can form while retaining a steep profile through much of its range. Read the paper here.

Tue 12 Mar 2024, 08:45 | Tags: BMS BMS_newpub

TimeTeller: A tool to probe the circadian clock as a multigene dynamical system

More and more evidence suggest that circadian clock disruption or misalignment is a feature of many diverse chronic diseases including metabolic syndrome, depression but also a number of cancers. For the latter, recent mechanistic studies in cancer models have established an understanding of how the circadian clock influences onset, progression and therapeutic outcomes. Moreover, it has been proposed that tumours might have disrupted circadian oscillators. In patients, however, this is more difficult to establish as usually only single samples, e.g., tumour biopsies, are available. Therefore, novel tools to measure the functional state of the molecular circadian clock are needed.

Here, we introduce TimeTeller, a machine learning tool that analyses the clock as a system and aims to estimate circadian clock function from a single sample’s transcriptome by modelling the multi-dimensional state of the clock. We demonstrate TimeTeller’s utility for analysing experimental in vitro and in vivo, as well as healthy human and patient samples from various platforms (microarray, RNA-Seq and NanoString) and highlight TimeTeller’s potential relevance for advancing circadian medicine. The project is an inter-disciplinary collaboration including significant work by Warwick’s MRCDTP students Laura Usselmann and Vadim Vasilyev and is setting the stage for further applications of TimeTeller in experimental models and human breast tumours.
Read the paper hereLink opens in a new window.

Tue 05 Mar 2024, 09:08 | Tags: BMS BMS_newpub

Personalized Chronomodulated 5-Fluorouracil Treatment: A Physiologically Based Pharmacokinetic Precision Dosing Approach for Optimizing Cancer Therapy

This work is based on the discovery of diurnal variations impacting cancer therapy. Especially, use of chronomodulated treatment with 5-fluorouracil (5-FU) has gained significance. Studies indicate high inter-individual variability in diurnal variations in dihydropyrimidine dehydrogenase (DPD) activity – a key enzyme for 5-FU metabolism. However, the influence of individual chronotypes on chronomodulated therapy was unclear but is needed to optimize precision dosing of chronomodulated 5‑FU. Lead by the Thorsten Lehr's PKPD group at the University of Saarland, this collaborative paper is taking a treasure trove of patient 5-FU PK data amalgamated with DPD enzyme activity data from health people to establish a novel PKPD model of 5-FU that captures the extent of diurnal variations in DPD activity and can help investigate individualized chronomodulated 5-FU therapy through testing alternative personalized dosing strategies. Read the paper here.

Thu 25 Jan 2024, 08:50 | Tags: BMS BMS_newpub

Dr Meera Unnikrishnan awarded over £2 million for research into C. difficile infection

Associate Professor Meera Unnikrishnan from the Division of Biomedical Sciences has been awarded a Wellcome Discovery Award from the Wellcome Trust to the value of £2,225,509. Her project, ‘Dissecting Clostridioides difficile-host-commensal interactions at the gut interface’, will take place over eight years.

Wed 06 Dec 2023, 11:54 | Tags: news BMS

Translational control of furina by an RNA regulon is important for left-right patterning, heart morphogenesis and cardiac valve function

Work by recent WMS PhD graduate Agnieszka Nagorska and PDRA Andreas Zaucker shows that translational control of an enzyme, FurinA, is important for normal positioning of the heart, and for cardiac valve function. FurinA cleaves the growth factor signal and morphogen, Nodal. Mutant zebrafish embryos with mis-regulated furina show premature and increased levels of FurinA, ectopic Nodal signalling, and defects in heart positioning and valve development. This is similar to human patients with mitral valve regurgitation. The findings pave the way for potential diagnostic tests for patients with heart valve dysfunctions. The work was supported by grants from the Leverhulme Trust, UKRI-BBSRC, MLSRF, and doctoral studentships from Warwick Medical School, MRC DTP, and Warwick-ARAP.
Read the paper hereLink opens in a new window.

Fri 01 Dec 2023, 17:01 | Tags: BMS BMS_newpub

Genome wide analysis revealed conserved domains involved in the effector discrimination of bacterial type VI secretion system

Gram negative bacterial pathogens use so called Type VI secretion systems (T6SSs) to deliver virulence effectors into target cells (either animal cells or other bacteria). Besides structural and effector proteins, many other proteins, such as adaptors, co-effectors and accessory proteins, are involved in this process. MIX domains can assist in the delivery of T6SS effectors when encoded as a stand-alone gene or fused at the N-terminal of the effector. However, whether there are other conserved domains exhibiting similar encoding forms to MIX in T6SS remains obscure.

In this work, we scanned publicly available bacterial genomes and established a database which include 130,825 T6SS vgrG loci from 45,041 bacterial genomes. Based on this, we revealed six domain families encoded within vgrG loci, which are either fused at the C-terminus of VgrG/N-terminus of T6SS toxin or encoded by an independent gene. Among them, DUF2345 was further validated and shown to be indispensable for the T6SS effector delivery and LysM was confirmed to assist the interaction between VgrG and the corresponding effector. Together, our results implied that these widely distributed domain families with similar genetic configurations may be required for the T6SS effector recruitment process.

Read the paper here.

Thu 30 Nov 2023, 08:44 | Tags: BMS BMS_newpub

History Repeats Itself: The Relevance of Historical Pandemics to the Medical School Curriculum

The dramatic global impact of the coronavirus pandemic has increased consideration on epidemiological progressions of pandemics. Measures implemented to reduce viral transmission have been largely historical, comparable in nature with the 1918 and 2009 influenza pandemics, demonstrating the importance of clinicians’ awareness on historical pandemics.

Read the paper here.

Fri 24 Nov 2023, 16:10 | Tags: BMS BMS_newpub

Assay_ready Cryopreserved Hepatocytes for Toxicity Testing

Liver hepatocytes are the front-line cells for screening new compounds for toxicity. However, hepatocytes are stored frozen in vials, not in monolayers meaning they need substantial processing to be ‘usable’ especially for high throughput screening. To solve this the Gibson and Dallman groups have collaborated, so show that immortalised and primary hepatocytes can be cryopreserved whilst attached to 96 well microplates. These can then be taken from the freezer, and simple thawed and are ready to use in under 24 hours. Post-thaw the cells show equal performance to fresh. This was achieved by careful consideration of the molecular mechanism damage during freezing, with the team using patent-pending controlled ice nucleation technology, rather than a traditional re-formulation of cryoprotectants approach. This work was in collaboration with Cryologyx, a University of Warwick Spin out, which has commercialised aspects of this technology.  
Read the paper hereLink opens in a new window.

Thu 26 Oct 2023, 12:57 | Tags: BMS BMS_newpub

Passive diffusion accounts for the majority of intracellular nanovesicle transport

Trafficking of proteins, lipids, and other molecules between cellular compartments is carried out by vesicular carriers. Material destined for transfer is packaged into a small trafficking vesicle at the donor compartment; the vesicle must then travel to its destination, before fusing with the target compartment to deliver the material.

Read the paper hereLink opens in a new window.

Thu 26 Oct 2023, 12:56 | Tags: BMS BMS_newpub

Congratulations - Class of 2023

Our 2023 Summer Graduation took place on Thursday 20 July, celebrating the fantastic achievements of our very first cohort of undergraduate BSc Health & Medical Sciences students, our MB ChB, Master's and PhD students.

Find out more.

Wed 16 Aug 2023, 15:04 | Tags: news HealthSciences BMS Graduation

Olive oil and fresh, sun-ripened plant-based foods: the Mediterranean Diet as a winning combination for health

Dr Thomas Barber says that to promote better health within Western societies, it's essential to reshape our food culture. This means moving away from unhealthy, ultra-processed, sugar-laden, and fibre-depleted foods and gravitating towards wholesome, fibre-rich, plant-based foods reminiscent of the Mediterranean diet.

Read the press release here.

Wed 09 Aug 2023, 08:24 | Tags: news BMS BMS_newpub

Pre-T cell receptor localization and trafficking are independent of its signaling

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.

Thu 03 Aug 2023, 10:36 | Tags: BMS BMS_newpub

Simple amino acids improve t-cell cryopreservation

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.

Thu 03 Aug 2023, 10:33 | Tags: BMS BMS_newpub

“Perfect" Glycosylated Materials

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.

Thu 03 Aug 2023, 10:31 | Tags: BMS BMS_newpub

High-throughput super-resolution analysis of influenza virus pleomorphism reveals insights into viral spatial organization

Andrew McMahon and others from the Robb lab have used super-resolution imaging to study the structure of the influenza virus, work which has just been published in PLOS Pathogens.
Influenza virus particles are highly pleomorphic, ranging in size from spherical virions ~ 100 nm in diameter to filaments of a similar width but reaching many micrometers in length. Virus structure is of interest not only in the context of virus assembly, but also because pleomorphic variations correlate with infectivity and pathogenicity. We used a super-resolution microscopy technique called dSTORM, which takes advantage of the blinking nature of fluorophores attached to viral proteins of interest to build up images of viral particles at <20nm resolution. Andrew then imaged thousands of virus particles and studied their shape and protein organization using high throughput analysis pipelines. We found that length analysis provided a useful way of characterizing virions and investigated the arrangement of viral proteins; demonstrating that no generalized spatial frequency patterning of HA or NA on the virion surface occurs, that the NA protein is polarized to the distal tip of budding filamentous virions, and that the RNA in filamentous virions is polarized towards one end of a filament. This study demonstrates the utility of fluorescence microscopy to study virus pleomorphism, and the importance of studying viral shape and organization to investigate their effect on infection dynamics.

Read the paper here.

Thu 03 Aug 2023, 10:29 | Tags: BMS BMS_newpub

Professor Stephen Royle is elected as the new Deputy Chair of the Board of Directors of the Company of Biologists

Tue 18 Jul 2023, 14:27 | Tags: BMS

Cryopreserving spheroids

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.

Fri 07 Jul 2023, 16:08 | Tags: BMS BMS_newpub

GibsonGroup discover material to prevent phage infection

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.

Fri 21 Apr 2023, 09:49 | Tags: BMS BMS_newpub

Genetically encoded imaging tools for investigating cell dynamics at a glance

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.

Thu 20 Apr 2023, 13:07 | Tags: BMS BMS_newpub

Fruit Fly helps Warwick Scientists Understand human heart development

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

Wed 05 Apr 2023, 09:19 | Tags: BMS BMS_newpub

Pathogen mapped for the first time – to understand evolution and potential treatments

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.

Read the press release hereLink opens in a new window.
Access the resource here and read the full paper here.

Tue 28 Mar 2023, 13:58 | Tags: BMS

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals

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.

Read the paper hereLink opens in a new window.

Tue 28 Mar 2023, 13:57 | Tags: BMS

Professor Andrew McAinsh granted £2.5M Wellcome Discovery Award

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.

Tue 14 Mar 2023, 11:18 | Tags: news BMS Research Wellcome

Inhibiting Ice Growth Using Polyproline

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.

Fri 03 Mar 2023, 15:26 | Tags: BMS BMS_newpub

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