Dr Hollie White, Assistant Professor in Health Sciences, and Theme Co-Lead for WMS BSc Health and Medical Sciences course has been appointed to the Board of Certification for Athletic Training International Committee (BOC-IC). For more information Click here

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.

Read the paper hereLink opens in a new window.

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.

Read the paper hereLink opens in a new window.

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).

Read the paper hereLink opens in a new window.

Congratulations to Dr Helen Nolan, Warwick Medical School, who was selected for an Education Innovation Award by the ASME’s Educator Development Committee (EDC). The ASME EDC Education Innovation Awards have been developed to highlight, promote and disseminate examples of innovative educational practice in healthcare professionals’ education.

Read the full news item here Dr Helen Nolan wins Education Innovation Award (warwick.ac.uk)

Congratulations to Professor Sian Taylor-Phillips who has been awarded a prestigious £1.8m NIHR Professorship to drive national policy for medical screening tests in the UK. She is one of six research leaders to receive this award, and the first at University of warwick, her research will consider the benefits and harms of population screening, which will help support government policy making. Read the full press release here

Warwick Medical School is delighted to welcome the new appointment of Professor Charles Craddock CBE to the Clinical Trials Unit as Professor of Haemato-Oncology. Professor Craddock will take a lead role in developing high-quality research programmes in clinical and cost effectiveness research of cancer therapies and support the University’s work on Innovation particularly in the health theme including the development of the University’s supra-regional health innovation campus Arden Cross and other projects - Read more here.

We reveal that the developing Drosophila nerve cord has a distinctive architectural structure, which is driven by JNK signalling.
Read the paper hereLink opens in a new window.

Dr Hannah James, Specialist Registrar in Trauma & Orthopaedic Surgery at UHCW and PhD graduate from Warwick Clinical Trials Unit has been awarded a very prestigious Hunterian Professorship by the Royal College of Surgeons for her ground breaking surgical education research work.

Dr James recently completed an outstanding body of research for her PhD on the impact of cadaveric surgical training on improving patient outcomes. She becomes the first female Trauma and Orthopaedic (T&O) surgeon to become a Hunterian Professor. Read the full article here

Seasonal winter peaks in infectious diseases put significant pressures on national health services, including hospitals and general practitioners. Respiratory Syncytial Virus (RSV) is a common virus which for the majority of people causes mild symptoms like a common cold, but it can be serious for very young infants and older adults. Currently, RSV is a significant contributor to pressures in paediatric intensive care. Find out more about how machine learning can predict the peaks in RSV and ultimately improve patient care - click here for more information

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.

Read the paper hereLink opens in a new window.

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.
Read the paper hereLink opens in a new window.

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.
Read the paper hereLink opens in a new window.

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.
Read the paper hereLink opens in a new window.

One of nine new Evidence Synthesis Groups (ESGs) has been awarded by the NIHR to a collaborative group, led by Professor Amy Grove and Dr Yen-Fu Chen from Warwick Evidence in Warwick Medical School. Read the full article here.

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.
See article hereLink opens in a new window.

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.
Read the paper hereLink opens in a new window.

We are delighted to announce that Professor Gavin Perkins has been appointed as Dean of Medicine for Warwick Medical School. He will commence his post from 1 August 2023. He will succeed Professor Sudhesh Kumar OBE who will step down after over eight years serving the WMS community as Dean and many more years than that as a senior leader within the School.

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.

A summary reportLink opens in a new window from the UK Commission on Bereavement (UKCB)Link opens in a new window was released earlier this week. Researchers in the UAPC were awarded a small grant from Marie Curie to provide a secondary analysis of the qualitative survey responses to contribute the commission report findings and recommendations.

The UKCB was set up to investigate and better understand the experiences of bereaved people and families, and how support and availability of support can be improved for them. This has become necessary due to the increase in number of people bereaved during the pandemic and the subsequent increased demand for bereavement support services. The UKCB was led by researchers and policy managers at Marie Curie but involved multiple charities, external researchers, and a PPIE advisory group with lived experience.

The report focuses on key challenges for both adults and children when experiencing a bereavement including practical death administration, communication with family and friends, and access to formal bereavement services. The report includes key recommendations for changes in policy and practice about how support for bereaved people could be improved, both now and in the long term.

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.

Read the paper hereLink opens in a new window.

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.
Read the paper hereLink opens in a new window.

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.

Read the paper here.

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.

Read the paper here.