AstraZeneca

Published on: 10 June 2014

Waste water can contain chemicals that are harmful to the environment, wildlife and human health. Image courtesy of Shutterstock.

Researchers at the University of Exeter and AstraZeneca are hoping to discover how cancer cells become resistant to some drugs, in a new study.

The work is just one of a series of collaborations between the University and the pharmaceutical development company that have taken place over the last 20 years. Joint projects have pushed the boundaries of science and delivered life-changing results that make a difference worldwide to people, wildlife and the environment.

Past collaborations have included projects looking at factors affecting the sensitivity and susceptibility of wildlife populations to certain chemicals, another developed new, more effective, chemical screening measures to identify potential adverse impacts. AstraZeneca has also worked with Exeter undergraduate students, one of which helped create a database to assist with the assessment of the environmental risk posed by medicines after patient use.

There are also a number of exciting new and ongoing collaborations.

Cancer

The cancer resistance work aims to help us tailor therapies to minimise the development of resistance to existing cancer drugs, and is being led by Exeter’s Dr Ivana Gudelj, an Associate Professor of systems biology, along with Exeter’s Professor Robert Beardmore.

Dr Gudelj said: “Most research at the moment is trying to understand how a single cell responds to a particular stress and what complex interactions happen within a cancer cell when it is exposed to a drug. The work we are doing is taking an ecological and evolutionary approach and looking at the cells as ecosystems.

“A lot of cancer centres do not apply these approaches. AstraZeneca was interested in trying something a bit different.”

The University’s computational biology group has worked on understanding how microorganisms adapt and become resilient to stressful environments such as drugs, temperature stresses, viruses etc for many years – the group are now applying this knowledge to cancer resistance.

The project came about after one of Professor Gudelj’s PhD students graduated and began working in AstraZeneca’s computational biology group. She was keen to maintain research links with Exeter and set up links between the two groups.

The cancer work is in its infancy, but Exeter’s Charles Tyler, a Professor of environmental biology, has been collaborating with AstraZeneca for more than 20 years.

Zebrafish

Working together Professor Tyler and the drugs-giant have developed test systems that help us better understand the potential environmental hazards and risks associated with some chemicals, including pharmaceuticals, that affect the body’s hormone systems (so called hormone disrupting chemicals). This work has helped inform the UK government and European Commission on the potential hazards of these chemicals and also played a part in the development of worldwide guidelines for chemical testing and the regulations that control the release of these types of chemical into the environment.

Professor Charles Tyler has been working with Astrazeneca for more than 20 years.

Some more recent collaborative research has seen Professor Tyler working with Dr Tetsu Kudoh to develop and apply transgenic zebrafish models to provide test systems that inform where chemicals act in the body.

The 2014 closure of AstraZeneca’s Brixham facility saw members of their zebrafish research team – Dr Malcolm Hetheridge, Dr Matt Winter, Dr Jonathan Ball and Maciej Trznadel brought into the College of Life and Environmental Sciences at Exeter to work alongside Professor Tyler. In this ambitious move, the team will undertake drug testing and develop new zebrafish models for research and healthcare protection.

Professor Tyler said: “This is an exciting venture for us, with these new and highly capable staff we hope to grow and expand our capability for internationally leading research into chemicals effects in animals to help better inform human and environmental health. The possibility of developing new model zebrafish systems that can serve to inform and protect both human and wildlife health is particularly exciting.”

Larval zebrafish can be used to detect drugs which can cause fetal harm, such as thalidomide. Dr Jane Stewart, the Global Head of Reproductive Toxicology at AstraZeneca explained: “Zebrafish assays [a system that enables you to say whether a compound has a certain type of effect] provide real hope of reducing the industry reliance on mammalian systems to detect agents that damage the foetus. The new team at Exeter are well placed to deliver industry leading capabilities.”

Adding significantly to the zebra fish team, a further leading researcher, Dr Lina Gunnarsson, will join them from Sweden in 2015.

Professor Tyler said: “Lina will help us to deliver a further part of this partnership with AstraZeneca in a project called exploring the feasibility of greener drug design, which is developing better procedures to assess and understand the environmental risks posed by medicines earlier in drug discovery and development.”

Lina will work on this project with Exeter PhD student and former AstraZeneca employee Gareth Le Page.

Collaboration

Professor Tyler hopes the partnership with AstraZeneca will continue to develop and said his relationship with them so far has been ‘fantastic’.

He added: “For me they have been one of the most progressive groups to interact and work with, certainly in terms of supporting high quality research. There has been good research success, including many publications with high impact.

“Successful partnerships with industries, such as with AstraZeneca, are all about finding the right people to link with. If you have good people and a good personal relationship, then an academic-industry partnership will work. Obvious, perhaps.”

The University and AstraZeneca are also investigating how antibiotics excreted into the environment contribute to bacterial resistance to these drugs – a problem that is difficult to reverse and poses a significant risk to human health. This project aims to develop tools to assess how resistance is developed when there are low levels of antibiotics in the environment; this work will support environmental policy developments in this field.

Antibiotics

It is well documented that over-prescription of antibiotics by doctors has contributed to increased resistance, but there has been less research into how antibiotic residues in our water systems could be contributing to the problem. Exeter student Aimee Murray’s AstraZeneca funded PhD, is looking into this.

Aimee’s PhD supervisor, Will Gaze, a molecular microbial ecologist at the European Centre for the Environment and Human Health explained: “Our collaborative work will study the chronic effects of antibiotic residues in aquatic systems. Although the potential for developing resistance may be less than at high antibiotic concentrations in the human body, the vast numbers of human and environmental bacteria mixing in aquatic systems means there is significant potential for new resistance mechanisms to be acquired by human associated bacteria in polluted environments.

“Many important resistance mechanisms are known to have originated in environmental bacteria, and the amount of resistance genes has been shown to increase through waste water treatment.”

Our relationship with the University of Exeter has been one of our most productive academic collaborations in terms of the science that we produce.

Dr Jason Snape, AstraZeneca Principal Environmental Scientist and Associate Director for Safety, Health and Environmental Research

He added: “AstraZeneca are very forward looking and identify organisations that have complementary expertise, in our case molecular microbial ecology. They have a long history of studying the environmental exposure and effects of pharmaceuticals. Their interest in this area fits extremely well with our research goals, which are to increase understanding of evolution of resistance in polluted natural environments.”

Dr Jason Snape, Principal Environmental Scientist and Associate Director for Safety, Health and Environmental Research within AstraZeneca said: “Our relationship with the University of Exeter has been one of our most productive academic collaborations in terms of the science that we produce, its international credibility, and the positive impact it has on the science underpinning pharmaceuticals in the environment and science-based environmental risk assessment.

“The closure of the Brixham facility has resulted in an increased reliance on partnerships, such as this one with the University of Exeter, to deliver some of the more strategic elements of our environmental research. We have the utmost confidence in the research groups within Exeter."

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