2018 news

31 October 2018

p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression

Carried out by researchers at the University of Leicester supported by the Division of Biomedical Services led by Ivano Amelio

Expression in cancer cells of novel proteins generated by mutations in the <emtp53<> gene is an important prognostic factor; however, how p53 mutants promote cancer progression is largely unknown. Here, we describe a molecular mechanism of gain-of-function by mutant p53 in hypoxic non-small cell lung cancer (NSCLC) cells. We identified the existence of a hypoxia-inducible factor-1 (HIF-1)/mutant p53 complex, exerting transcriptional control of a specific subset of protumorigenic genes, codifying for extracellular matrix (ECM) components. Employing in vivo cancer models and analyzing clinical material, we demonstrate that these ECM components substantially contribute to the synergistic protumorigenic activity of p53 mutants and HIF-1. Our data indicate that HIF-1/mutant p53 cross-talk is an innovative potential therapeutic target to treat advanced NSCLC.</emtp53<>

• Find out more from Proceedings of the National Academy of Sciences of the United States of America

20 September 2018 

A preclinical ultrasound method for the assessment of vascular disease progression in murine models 

Studies carried out by researchers at the University of Leicester supported by the Division of Biomedical Services led by Michael Kelly.

The efficacy of preclinical ultrasound at providing a quantitative assessment of mouse models of vascular disease is relatively unknown. In this study, preclinical ultrasound was used in combination with a semi-automatic image processing method to track arterial distension alterations in mouse models of abdominal aortic aneurysm and atherosclerosis.

• Find out more from Sage Journals.

20 September 2018

Pig spleens sourced from abattoirs could help reduce the need for live animal testing, research shows

Study led by researchers from University of Leicester and Leicester’s Hospitals provides useful information for improving our understanding of infections such as pneumonia and sepsis

New research published by researchers from the University of Leicester, Leicester’s Hospitals and University College London (Dr Giuseppe Ercoli, who was a post-doctoral researcher at Leicester at the time the work was conducted, now works at UCL) has developed a scientific model that could replace the use of protected animals in research with abattoir-sourced pig spleens - potentially reducing the need to conduct experiments on animals.

The team set out to study bacterial infection in human spleens, the main organ responsible for innate immunity, in order to improve our understanding of invasive infections including pneumonia and sepsis.

In order to do this, the team studied ex vivo pig spleens - retrieved from animals slaughtered for food production - which can act as a reliable parallel to human spleens and allow for scientists to explore how certain infections and diseases can affect humans with a high degree of accuracy. 

“To study mechanisms of immune response to infection we need experimental models,” says Professor Marco Oggioni. “To be able to do so without the need to breed animals for experimental research and to expose animals to any suffering due to experimental research is a breakthrough. The use of abattoir-sourced organs removes this problem, by still providing us with excellent scientific data.

“This is an important occasion and highlights the University of Leicester’s commitment to the principles of the 3Rs - Replacement, Reduction and Refinement - in animal research.”

The methodology of ex vivo perfusion indicates that organs are taken from deceased animals and perfused with blood or blood-replacement, keeping them functional for a period of many hours. During this period, how the organ responds to agents such as bacteria can be studied - including testing therapeutic interventions against infections.

• The paper, ‘An ex vivo porcine spleen perfusion as a model of bacterial sepsis‘, is published in the journal ALTEX: Alternatives to Animal Experimentation.

20 September 2018 

Understanding Animal Research (UAR)

Two technicians from the Division of Biomedical Services delivered a presentation on Understanding Animal Research to students at Stephenson Studio School in Coalville.  This was part of their STEM learning timetable.

20 September 2018 

Reducing variability in experimental stroke models

Leicester study offers an opportunity to reduce the number of animals used in stroke research led by Claire Gibson's research group, supported by the Division of Biomedical Services.

A study by our University, recently published in Disease Models & Mechanisms, describes a new approach for inducing stroke in mice that reduces variability in the experimental model. The work, funded by an NC3Rs pilot study grant to researchers at the University of Leicester, offers an opportunity to reduce the number of animals used in stroke research.

• Find out more from NC3Rs.

20 September 2018 

Tinnitus study (published in Experimental Neurology)

Study carried out by researchers at the University of Leicester supported by the Division of Biomedical Services let by Martine Hamann's research group found that Magnesium could offer fresh hope to tinnitus sufferers.

• Find out more from The Conversation.

20 September 2018 

Research reveals air pollution can alter the effectiveness of antibiotics and increases the potential of disease

Leicester research reveals the impact of black carbon on bacteria in the respiratory tract, studies led by Julie Morrissey's research group.

Air pollution is the world's largest single environmental health risk (WHO). Particulate matter such as black carbon is one of the main components of air pollution. The effects of particulate matter on human health are well established however the effects on bacteria, organisms central to ecosystems in humans and in the natural environment, are poorly understood. We report here for the first time that black carbon drastically changes the development of bacterial biofilms, key aspects of bacterial colonisation and survival. Our data show that exposure to black carbon induces structural, compositional and functional changes in the biofilms of both S. pneumoniae and S. aureus. Importantly, the tolerance of the biofilms to multiple antibiotics and proteolytic degradation is significantly affected. Additionally, our results show that black carbon impacts bacterial colonisation in vivo. In a mouse nasopharyngeal colonisation model, black carbon caused S. pneumoniae to spread from the nasopharynx to the lungs, which is essential for subsequent infection. Therefore our study highlights that air pollution has a significant effect on bacteria that has been largely overlooked. Consequently these findings have important implications concerning the impact of air pollution on human health and bacterial ecosystems worldwide.

• Find out more from Wiley Online Library.