Bioluminescent imaging in induced mouse models of endometriosis reveals differences in four model variations
Our understanding of the etiology and pathophysiology of endometriosis remains limited. Disease modelling in the field is problematic as many versions of induced mouse models of endometriosis exist. We integrated bioluminescent imaging of ‘lesions’ generated using luciferase-expressing donor mice. We compared longitudinal bioluminescence and histology of lesions, sensory behavior of mice with induced endometriosis and the impact of the GnRH antagonist Cetrorelix on lesion regression and sensory behavior. Four models of endometriosis were tested. We found that the nature of the donor uterine material was a key determinant of how chronic the lesions were as well as their cellular composition. The severity of pain-like behavior also varied across models. Whilst Cetrorelix significantly reduced lesion bioluminescence in all models, it had varying impacts on pain-like behavior. Collectively, our results demonstrate key differences in the progression of the ‘disease’ across different mouse models of endometriosis. We propose that validation and testing in multiple models, each of which may be representative of the different subtypes / heterogeneity observed in women should become a standard approach to discovery science in the field of endometriosis. Read the paper here
Dual pH-Responsive Macrophage-Targeted Isoniazid Glycoparticles for Intracellular Tuberculosis Therapy
With the support of the Wellcome-Translational Partnership, the teams of Dr Meera Unnikrishnan and Professor Sebastien Perrier have developed a new family of nanoparticles for the treatment of TB infection which address the main shortfall of current therapies, poor penetration to mycobacterium containing niches such as macrophages.
The team has designed mannose-decorated nanoparticles loaded with a well-established TB drug, which can degrade and deliver their payload at lysosomal pH. Fluorescence uptake studies showed preferential endocytosis of mannosylated particles via sugar-lectin interactions, and the particles were also shown to be effective at killing intracellular M. bovis BCG bacteria in THP-1 macrophages. Taken together these results show that in vitro, such macrophage-targeted particles increase intracellular isoniazid concentration, showing an increased antimicrobial activity against intracellular mycobacteria. Read the paper here
Calponin-homology domain mediated bending of membrane associated actin filaments
This paper was the result of a collaboration between Saravanan Palani (now at IISC Bangalore), Darius Köster and Mohan Balasubramanian. Here we show that the extended CH domain of IQGAP proteins such as Rng2 or IQGAP1 can bend usually straight actin filaments into tight rings when tethered to a lipid membrane. That observation was quite unexpected as no other protein is known to do this! It was a control experiment that allowed us to make this fascinating observation… read more here
NanoSyrinx raises £6.2m
NanoSyrinx, a spin-out from the Waterfield Lab at Warwick Medical School founded by Dr Joe Healey and Dr Nick Waterfield, announced on Monday that it had successfully raised a further £6.2M in seed financing. This builds on an initial fundraising in early 2020, and the company will use the funds to continue developing its platform – a novel biologic drug delivery system utilising genetically encoded “nanosyringes” – toward pre-clinical proof of concept over the next two years.
Further details here
A protein involved in making cells move offers a clue to how certain types of cancer metastasize and develop into secondary tumours, according to new research from WMS.
Early migrations of Siberians to America tracked using bacterial population structures
International team used the stomach bacteria Helicobacter pylori as a biomarker for ancient human migrations
DNA sequences catalogued at University of Warwick in EnteroBase, a public genomes database, demonstrate that a migration of Siberians to the Americas occurred approximately 12,000 years ago
Project began in 2000s but new statistical techniques allowed researchers to reconstruct and date the migrations of Siberian Helicobacter pylori
Early migrations of humans to the Americas from Siberia around 12,000 years ago have been traced using the bacteria they carried by an international team including scientists at the University of Warwick.
Impact of the protein corona on nanoparticles
The Gibsongroup are developing nanoparticles for biosensing, diagnostics, and delivery applications. A key challenge is how particles perform in ‘perfect’ conditions verses ‘real world’ when proteins found in blood can ’stick’ to the surface and compromise performance.
In their latest paper they show how nano-rods, with glycans on their surface, do indeed get ‘fouled’ by proteins, but show how this does not prevent their use in biosensing, and that in fact the release of serum proteins can be used to generate signal.
Read the paper here
Cryopreserving blood cells with polymers
The cryopreservation of cells and tissues is crucial in biomedical research and in modern medicine. Red blood cells are crucial and are currently stored in glycerol. In the latest work from the GibsonGroup they show that an unconventional cryopreservation mixture, including synthetic polymers, can be used to protect red blood cells during freezing and results in high recovery, even with larger volumes. Crucially, this mixture is very easy to wash-out post-thaw.
Read the paper here
Warwick Medical School authors, Dr Helen Atherton, Dr Jo Parsons and Dr Carol Bryce looked at the rate of missed GP appointments in the UK. Their findings are published in the BJGP and Jo Parsons is also interviewed in a podcast discussing some of the findings and implications of this work.
Missed general practice appointments have considerable time and cost implications for the NHS, and leaves patients with unmet health needs, and potentially delayed diagnoses or medical treatment. This systematic review, entitled ‘Which patients miss appointments with general practice and the reasons why’ updated work conducted in 2003, and aimed to examine the rate of missed booked appointments, which patients are more likely to miss appointments, and some reasons for this. Findings of this review has potential implications for practices in targeting interventions to patients that are at increased likelihood of missing appointments, and in attempting to overcome common reasons that appointments are missed.
More information can be found on the GP Online webpages here.
T cells discriminate between healthy and infected cells with remarkable sensitivity when mounting an immune response, which is hypothesized to depend on T cells combining stimuli from multiple antigen‐presenting cell interactions into a more potent response. To quantify the capacity for T cells to accomplish this, we have developed an antigen receptor that is optically tunable within cell conjugates, providing control over the duration, and intensity of intracellular T‐cell signalling.
Ethnicity-specific BMI cutoffs for obesity based on type 2 diabetes risk in England: a population-based cohort study
Researchers from four leading institutions (University of Warwick, Oxford University, The London School of Hygiene & Tropical Medicine and the UCL Institute of Health Informatics) came together in partnership with the Ethnic Health Forum to create this population-based cohort study using linked primary care and secondary care electronic records from England.
This study’s findings come at a critical time, given the increased focus on health inequalities affecting millions of people from minority ethnic communities as well as the link between obesity and COVID-19 (a condition also adversely affecting UK BAME people).
Read the press release here
Read the article here
Unravelling the role of proline in cryopreserving cell monolayers
The cryopreservation of cells as adherent monolayers is very challenging, compared to in suspension The GibsonGroup's latest work explores the role of proline in ‘preparing’ cells for cryopreservation, observing they slow growth rates, and enable more cells to recover from cryopreservation compared to without proline. Read the paper here
Small ice binding peptides from phage display
The GibsonGroup have collaborated with Prof Harm Anton Klok at EPFL, and the Sosso Lab at Warwick to discover new, small, ice binding peptides. The team used phage display to screen billions of possible sequences, to identify a 14 amino acid cyclic peptide than can bind ice crystals. The peptide was a potent ice growth inhibitor and the use of the as a ‘CryoTag’ to purify proteins via ice-binding was demonstrated. This will help develop new cryoprotectants and an understand of how proteins can recognise ice, in a large excess of water.
Biomimetic Polymer Particles to Control Ice Growth
The GibsonGroup have reported a surprising result that larger (several hundred nanometres) polymer nanoparticles can stop ice recrystallisation, and in some cases bind to the ice - a feature commonly associated with ice binding proteins from extremophiles. The team used a technique termed polymerization-induced self-assembly to produce the particles, which is appealing as they can be made at scale and are highly tunable, compared to producing proteins. These materials will be explored as part of the team's cryobiology research.
Unwrapping a cellular mystery
Chromosome segregation during cell division is carried out by the mitotic spindle, a tiny machine composed of microtubules, motors and associated proteins. Mitosis in human cells is ‘open’, meaning that the nuclear envelope breaks down at prophase.
This is in contrast to ‘closed’ mitosis in lower species. Cell biologists studying mitosis have therefore focused on the mitotic spindle, paying little attention to cellular membranes and organelles in the cell. We have known since the 1950s that the spindle sits in a membrane-free “exclusion zone”, which mimics a closed mitosis system. Outside this zone is a sea of densely packed ER/nuclear envelope and other organelles (collectively called endomembranes).
This begs the question: what happens to chromosomes that find themselves amongst the endomembranes outside the exclusion zone?
Our study show that chromosomes not aligned by the spindle can become ensheathed in multiple layers of endomembranes. This event consigns the chromosome to missegregation and generates a micronucleus that is associated with genomic rearrangements that may drive tumour evolution. We developed a new strategy to clear the ER from live mitotic cells and find that these ensheathed chromosomes could be rescued by the mitotic spindle. We conclude that ensheathing constitutes a novel pathway to aneuploidy.
Black women face a significantly higher risk of having a miscarriage than white, according to research involving Prof Siobhan Quenby from WMS.
Depletion of a certain type of stem cell in the womb lining during pregnancy could be a significant factor behind miscarriage, according to a study by Warwick Medical School researchers.
We're delighted that our new Interdisciplinary Biomedical Research Building, which we will share with the School of Life Sciences, is now complete, bringing to life Warwick's commitment to delivering world-leading research in neuroscience, microbiology and infection, cell biology, and disease models.
We are pleased to share news that eight members of the WMS community have secured Fellowships with the University's Institute of Engagement.
On the UN's International Day of Women and Girls in Science, the University spoke to some our researchers and asked them about their hopes for their research and the importance of equality in their chosen field.
CryoLogyx spin out from GibsonGroup
A new spin out company has been awarded funding from innovateUK to develop new frozen cell products. The company will use technology developed in the Gibsongroup which uses synthetic polymers to protect cells (and other biologics) during freezing, and to make them easier to transport and deliver. The company is being led by a postdoc in the group, Dr Tom Congdon.
Read the press release here
Read about the group’s research here
Using unnatural sugars to target galectins
The GibsonGroup, as part of a large BBSRC/Innovate funded collaboration have published their latest results into using nanomaterials to probe glycan-binding events. In this collaborative work, a combined chemical and enzymatic synthetic route was exploited to generate glycans which could be attached to nanoparticles for glycan/lectin screening - a platform technology developed by the GibsonGroup. Using this approach, it was shown that selective addition of fluorine atoms allow selective binding of galectins which is not possible using natural disaccharides, and may offer a route for targeting therapies and diagnostics. https://doi.org/10.1039/D0SC05360K
Modelling of SARS-CoV-2 reinfection frequency
One of the key questions in predicting the course of the COVID-19 pandemic is how well and for how long the immune response to the virus protects people from reinfection. The Robb group modelled early SARS-CoV-2 infection and fatality data from different regions around the world to predict how many reinfection cases would be expected if there was no immunity to the disease. Numerous serological studies now support the conclusion that short-term immunity to the virus exists. doi:10.2196/21168
The College of Pathologists' annual International Pathology Day Conference recognises and celebrates the contribution and achievements of pathology and laboratory medicine services that work to address global health challenges and improve the health outcomes of global communities.
New diagnostic test detects and identifies SARS-CoV-2 virus in less than five minutes
Scientists, led by Dr Nicole Robb, have developed an extremely rapid diagnostic test that detects and identifies viruses in less than five minutes. The test uses artificial intelligence to distinguish between microscope images of fluorescent viruses in throat swab samples. Unlike other technologies that detect a delayed antibody response or that require time-consuming sample preparation such as viral lysis or amplification, the new test quickly detects intact virus particles; meaning the assay is simple, fast and has the potential to be carried out in non-laboratory conditions. Read about the research here