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The influence of extrachromosomal elements in the anthrax "cross-over" strain Bacillus cereus G9241

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.

Wed 03 Aug 2022, 14:55 | Tags: BMS BMS_newpub

From cereus to anthrax and back again: The role of the PlcR regulator in the “cross-over” strain Bacillus cereus G9241

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.

Wed 03 Aug 2022, 14:52 | Tags: BMS BMS_newpub

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

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.

Mon 01 Aug 2022, 10:45 | Tags: news BMS BMS_newpub

All hail the mighty MitoPits!

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.

Fri 29 Jul 2022, 15:12 | Tags: BMS BMS_newpub

Using amino acids to control ice growth

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.

Mon 20 Jun 2022, 15:09 | Tags: BMS BMS_newpub

Characterisation of the Ubiquitin-ESCRT pathway in Asgard archaea sheds new light on origins of membrane trafficking in eukaryotes

This work answers the mystery surrounding when in evolution did a key class of membrane remodelling factors arise. The collaborative team comprising Balasubramanian (Warwick), Baum (Cambridge), Lowe (Cambridge), Robinson (Lancaster), and Ettema (Wageningen, Netherlands) worked on proteins encoded by Heimdall archaea, thought to be most related to eukaryotes. They found that, contrary to existing dogma, a complex eukaryote-like ESCRT family of membrane remodelling factors were present in archaea and are therefore not eukaryotic inventions. Warwick post-doctoral fellow and first author Hatano “reconstituted” key steps of the process using purified components helping arrive at the conclusions.
Read the paper hereLink opens in a new window.

Wed 18 May 2022, 09:02 | Tags: BMS BMS_newpub

Cancer origin identified through cell ‘surgery’

Research from the University of Warwick sheds new light on a key cause of cancer formation during cell division (or mitosis), and points towards potential solutions for preventing it from occurring.

Thu 05 May 2022, 09:05 | Tags: news BMS BMS_newpub

Development is more than just growth: Understanding the mechanics of organ shrinkage during embryo formation

When we think about embryo growth, we often focus on tissue growth. However, this is not always the case: for example, the nervous system actually shrinks during parts of development. How do tissues condense in size while maintaining mechanical integrity? In recent work from the Saunders lab, with Spanish collaborators Enrique Martin-Blanco and Jose Munoz, they show that the Drosophila nervous system condenses through alternating waves of contraction from the anterior and posterior ends of the embryo. Further, they use the power of Drosophila genetics to reveal that the glial cells provide an essential mechanical support, effectively acting like a compression sock during condensation. This work opens up new avenues to study the mechanobiology of tissues that shrink – such tissues display behaviour very much distinct from growing tissues. Read the paper here.

Fri 29 Apr 2022, 15:19 | Tags: BMS BMS_newpub

Getting the embryo into position

During development, many organisms initially undergo multiple rounds of nuclei division before cellularisation occurs. Such systems are known as syncytia. Other processes such as muscle formation – which have multiple nuclei in a single cell – are similar.

In syncytia, nuclei distribute in a regular pattern. Yet, how does this occur? Answering this question is important for understanding how life developments and muscles form. In recent work from the Saunders lab, in collaboration with the Telley lab at the Gulbenkian Institute in Portugal, they used quantitative measurements to unravel how the nuclei regularly position in the fruit fly syncytium. They took advantage of explants – whereby material is removed from the egg and imaged – to reveal that are repulsive interactions between microtubules (rod like structures) in the syncytia. They used modelling and experimental tests to show that these repulsive interactions drive the ordering of the nuclei.

Read the paper here.

Thu 03 Feb 2022, 15:50 | Tags: BMS BMS_newpub

Cell-Type-Specific Circadian Bioluminescence Rhythms in Dbp Reporter Mice

In collaboration with groups at UMass Med School, Smith College and Morehouse University, we have developed a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein (Dbp). In this line of mice, firefly luciferase is expressed from the Dbp locus in a Cre recombinase-dependent manner, allowing assessment of bioluminescence rhythms in specific cellular populations. Our studies reveal cell-type-specific characteristics of rhythms among neuronal populations and liver cells. Our model allowed assessment of the rate of recovery from circadian misalignment once animals were provided with food ad libitum. These studies confirm the previously demonstrated circadian misalignment following environmental perturbations and reveal the utility of this model for minimally invasive, longitudinal monitoring of rhythmicity from specific mouse tissues.

Read the paper here.

Mon 17 Jan 2022, 08:00 | Tags: BMS BMS_newpub

Lighting Up Tumour Treatments

The Perrier Lab have just published a new study in Angewandte Chemie which shows how polymeric nanotubes can be designed to switch their fluorescence on as they deliver a commercial anticancer drug (doxorubicin), thereby permitting the in-situ visualization of drug release. By this method, we can both treat a cancer tumour and show where the tumour is located. These theranostic systems (from therapeutic and diagnostic) form a new approach to drug delivery.

Read the paper here.

Fri 14 Jan 2022, 15:30 | Tags: BMS BMS_newpub