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.

Much cell biology, biomaterials and associated research is conducted on cells attached to tissue culture plastic in multiwell plates - such as high throughput drug discovery and toxicity, to viral plaque assays. However, there is a disconnect that the cells are stored frozen in suspension, not in the format ‘ready to use’. This is because conventional cryoprotectants do not protect the cells when in monolayer format. The GibsonGroup, and UoW Spin-Out Cryologyx have worked together to solve this problem using macromolecular cryoprotectants. In this later paper, the team demonstrate reproducilble and robust recovery of cell monolayers out of the freezer. This is shown for common cell lines, including HepG2 and Caco-2, commonly used in drug screening. This is a revolutionary technology as it shows researchers could stop wasting time culturing cells, and just order them, remove from freezer and within 24 hours begin data collection with no of the traditional culturing steps. Cryologyx are deploying these findings to commercialise assay ready cells, and trial plates are available!

Read the paper here.

A new technique for freezing cells for use in biomedical research, based on polymer technology developed at the University of Warwick, has been validated in study, paving the way for faster results for scientists in their research.

We recently interviewed Dr Shahed Yousaf, Warwick Medical School alumnus who graduated in 2006. He lives in Birmingham and has been a GP for ten years working with the homeless and with prisoners. He is also an accomplished writer, starting off his writing career with fiction, he has now published ‘Stitched Up’ which follows his career in medicine working with patients on the edge of society.

All cells must accurately separate their chromosomes during mitosis to avoid errors that are associated with cancer development, reproductive failure and even ageing. This feat is accomplished by the mitotic spindle – this microtubule-based machine has a bipolar geometry and contains hundreds of protein components. A subset of microtubules form bundles that make contact with kinetochores on the chromosome (these are called K-fibres). The growth and shrinkage of these microtubules, through addition and loss of tubulin, is coupled to the hydrolysis of GTP: this powers chromosome movement. Previous work identified a protein called HURP (hepatoma up-regulated protein) that forms distinctive stripes on each half spindle (see schematic). Here, through collaboration with University of Geneva, we identified a new region within the mitotic spindle, termed “HURP-gap”. This HURP free region of the K-fibre is located between the stripe and the kinetochore.

Discovery: How do organs reach a specific size during development? The Hippo/YAP pathway has been identified as a critical regulator of organ size control. It also plays an important role in homeostasis and cancer progression, in part due to its mechanosensitive response. Here, the Saunders lab have developed an optogenetic version of YAP (optoYAP) that enables its localisation to the nucleus to be tightly controlled in both space and time. This enables targeted perturbation of the pathway, with potential applications to wound healing and regeneration.
Read the paper hereLink opens in a new window.

The GibsonGroup are developing macromolecular (polymer) cryoprotectants to enable next-generation cell based therapies, and to simplify cell-based assays. A key feature identified in the teams most potent materials is a mixture of cationic/anionic charges on the side chain, but the exact mechanism of action is under investigation. In this latest work the team explored sulphoxide (‘DMSO like’) side chains, which are actually highly polarised with S+-O- character. The team also explore N-oxide polymers which have similar charged character. Using a range of phyical and biochemical assays the team investigated if these motifs could aid in cryopreservation.
Read the paper hereLink opens in a new window.

The Data Science and Artificial Intelligence showcase will be held at Warwick this year and is open to anyone in the research teams and wider audiences active in Data Science and AI.
The two keynote speakers are directly aligned to Women in STEM, with Anne-Maire Imafidon almost confirmed as the closing plenary speaker.

There will also be a poster exhibition, and full details on how to enter can be found with this link Poster Competition - submissions just need to be a high-res PDF, all printing costs are covered and there are a few prizes up for grabs.
Register here and join us to debate  

We have now published back to back two papers on the so called anthrax “cross over strain Bacillus cereus G9241. The first paper (From cereus to anthrax and back again: The role of the PlcR regulator in the “cross-over” strain Bacillus cereus G9241) has already been highlighted. This current paper is titled, “The influence of extrachromosomal elements in the anthrax “cross-over” strain Bacillus cereus G9241.”

The work investigates the contribution of anthrax-like plasmids and a lysogenic phagemid to the pathogenic potential of the normally relatively harmless Bacillus cereus. We investigated the role of temperature and carriage of the pBCXO1 plasmid (which is homologous to the pXO1 anthrax toxin plasmid) in regulation of chromosomal genes, heavily affecting metabolism. In addition we have shown that sporulation of G9241 is very rapid at 37’C, which is characteristic of B. anthracis but unlike the ancestral B. cereus strains. Finally we isolated phagemid virions which are produced at 37’C and visualised them with electron microscopy.

Read the paper here.

In our recent paper “From cereus to anthrax and back again: The role of the PlcR regulator in the “cross-over” strain Bacillus cereus G9241” we have investigated how a normally low risk Bacillus cereus strain has evolved to mimic Bacillus anthracis, the causative agent of the highly feared lethal anthrax infection. The B. cereus G9241 strain is one of several relatively recent isolates that are termed “anthrax cross over strains” that intriguingly seem to preferentially infect metal workers in the USA (welders / millers). These strains are of particular concern as, unlike B. anthracis proper, they can switch between a form that can survive and replicate in the environment using invertebrate hosts and the more lethal mammalian infective anthrax like form. B. anthracis must pass from mammalian host to mammalian host as a spore form thus somewhat limiting its spread. This is due to a loss of function mutation in a key regulator protein named PlcR, which in all other B. cereus sensu lato group strains allows for survival outside of a mammalian host. Our work has identified the specific mechanism by which G9241 can switch on and off the PlcR regulation endowing it with a “Dr. Jekyll or Mr. Hyde” like life cycle. This work was a culmination of a Marie Curie fellow, 3 PhD students and one postdoc and was supported by MoD Porton Down DSTL funding and advice, for which we are very grateful.

Read the paper here.

Our 2022 summer graduation took place on 21 July, celebrating the fantastic achievements of our MB ChB, Master's and PhD students.

We’re delighted to announce that two of our 2022 MB ChB graduates, Gabriela Barzyk and Charlotte Simms, have been awarded Outstanding Student Contribution Awards from the University of Warwick.

One of the key questions relating to the COVID-19 pandemic is how prior immunity to related endemic coronaviruses affects the SARS-CoV-2 immune response. In this study, we provide evidence of immunological imprinting in individuals with fatal outcomes from COVID-19, suggesting an antibody profile consistent with an original antigenic sin type-response. Read the paper hereLink opens in a new window.

Cansu Küey’s PhD work was published this week in eLife. Together with Méghane, Gabrielle and Miguel, she showed that clathrin-coated pits can be made to form on intracellular membranes. This phenomenon allowed us to redefine two key concepts in clathrin-coated vesicle formation. First, a scission molecule is not needed to pinch off vesicles inside the cell. Second, that most of the other proteins found in regular clathrin coats are not essential for vesicle formation.

Robots will have their surgical skills put to the test as researchers from Warwick Medical School trial their use in hip replacement surgery for the first time.

Many congratulations to Harbinder Sandhu, Professor of Health Psychology, who has been highly commended at the Asian Women of Achievement Awards UK 2022.

Tommer Spence has been awarded a PhD in Health Sciences for their PhD on ‘The Perceptions and Experiences of Using Internet-Based Testing for Sexually Transmitted Infections’. Tommer was supervised by Frances Griffiths in the Division of Health Sciences and Jonathan Ross.

Kirstie Shearman has been awarded a PhD in Health Sciences for her PhD on ‘Improving Information for Research Participation’. Kirstie was supervised by Heather Draper and Greg Moorlock in the Division of Health Sciences.

Monday 11 July, 12.00pm, GLT3 - Please note change of date

Dr David Gregor-Kumar, the BBC West Midlands Science Correspondent, will be coming to talk to the network. Come along and learn how to speak about your research and teaching on the radio or TV and counteract the under-representation of women scientists who broadcast their findings. Please let Stephanie Smart (s.smart@warwick.ac.uk) know if you are planning on attending for numbers and catering purposes, along with any dietary requirements.

The GibsonGroup, in collaboration with the Sosso Group (chemistry) are investigating how small molecules can inhibit ice recrystallisation - a property more commonly associated with macromolecules, such as ice binding proteins or some polymers. The challenge of the macromolecules is that sequential modification is challenging, and hence structure-property relationships are often missing. Here the team show that phenyl alanine can inhibit ice recrystallisation and that modulation of the hydrophobic face impacts the magnitude of the activity. This work shows that ’small molecule’ approaches can be taken to probe the complex ice/water interface, with the long term goal of finding new molecules to control ice growth.

Read the paper here.

During the Covid-19 pandemic hospice care across the West Midlands fell below the “gold-standard” despite the best efforts of frontline healthcare professionals. This news has been revealed in a report from the end of life charity Marie Curie, based on research from WMS led by Dr John MacArtney. Read the university's press release hereLink opens in a new window and the full report and films explaining the study and findings hereLink opens in a new window.

During the Covid-19 pandemic hospice care across the West Midlands fell below the “gold-standard” despite the best efforts of frontline healthcare professionals, according to a report from the end of life charity Marie Curie, based on research from Warwick Medical School.

Warwick MB ChB finalist Thomas Dale MacLaine recently attended a garden party at Buckingham Palace in recognition of his services to Higher Education. We caught up with him to find out more about the experience and why he was recognised.

Our 2022 MB ChB Prizegiving Evening took place on 11 May, celebrating the fantastic work and achievements of our medical students over the last year and excellence amongst our staff.