̽��ֱ�� of Cambridge - biomedical

Cambridge researchers elected to Academy of Medical Sciences Fellowship 2023

lw355 — Thu, 18 May 2023 08:00:52 +0000

̽��ֱ��new Fellows have been elected to the Academy in recognition of their exceptional contributions to the advancement of biomedical and health science, cutting-edge research discoveries and translating developments into benefits for patients and wider society.

They join a prestigious Fellowship of 1,400 esteemed researchers who are central to the Academy’s work. This includes providing career support to the next generation of researchers and contributing to the Academy’s influential policy work to improve health in the UK and globally.

Professor Dame Anne Johnson PMedSci, President of the Academy of Medical Sciences, said: “These new Fellows are pioneering biomedical research and driving life-saving improvements in healthcare. It’s a pleasure to recognise and celebrate their exceptional talent by welcoming them to the Fellowship.

“This year, we are celebrating our 25th anniversary. ̽��ֱ��Fellowship is our greatest asset, and their broad expertise and dynamic ability has shaped the Academy to become the influential, expert voice of health. As we look to the future, the collective wisdom our new Fellows bring will be pivotal in achieving our mission to create an open and progressive research sector to improve the health of people everywhere.”

̽��ֱ��new Cambridge Fellows are:

Professor Charlotte Coles FMedSci

Professor of Breast Cancer Clinical Oncology, Department of Oncology, NIHR Research Professor and Director of Cancer Research UK RadNet Cambridge

Professor Coles leads practice-changing breast radiotherapy trials, has influenced international hypofractionation policy and is addressing global health, gender and equity challenges within the Lancet Breast Cancer Commission.

“It’s an honour to be elected as a new Fellow of the Academy of Medical Sciences. This is a result of research collaborations in Cambridge, the UK and internationally and I’d like to thank these wonderful colleagues, especially patient advocates,” said Coles.

“I hope to contribute to the Academy’s work to increase equity, diversity and inclusion within leadership roles, including lower- and middle-income countries, to enrich research and improve the culture in Medical Sciences.”

Professor Emanuele Di Angelantonio FMedSci

Professor of Clinical Epidemiology and Donor Health, Department of Public Health and Primary Care, and Head of Health Data Science Centre, Human Technopole (Milan)

Professor Di Angelantonio’s research has focused on addressing major clinical and public health priorities in cardiovascular disease (CVD) and transfusion medicine. His election recognises his many contributions both in helping resolve important controversies in CVD prevention strategies and in improving the safety and efficiency of blood donation.

“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences, which I recognise is an outcome of the collaborations with many colleagues in UK and worldwide,” said Di Angelantonio.

“Research excellence across medical sciences and translation to health improvements has been at the centre of the Academy’s mission and I am very pleased to now be able to contribute to fulfilling this aim as a Fellow.”

Dr Rita Horvath FMedSci

Director of Research in Genetics of Rare Neurological Disorders in the Department of Clinical Neurosciences and Honorary Consultant in Neurology

Dr Horvath is an academic neurologist using genomics and biochemistry to diagnose rare, inherited neurological disorders, with a focus on mitochondrial diseases. Throughout her career she has combined fundamental experimental work with clinical studies. She pioneered the development and implementation of next generation sequencing in the diagnosis of rare neurogenetic diseases in the UK, leading to precision genetic approaches. She has established extensive international collaborations, having impact in Europe, but also for underserved groups in countries where such expertise is lacking.

“I am delighted and honoured to be elected to this Fellowship, which recognises the impact of my work. I would not have achieved it without the support of my excellent colleagues and research team, for which I give my sincere thanks,” said Horvath.

“As a Hungarian woman working in different countries before I arrived in the UK in 2007, I feel particularly proud of this award, which I recognise is an outcome of the open and fair research environment in Cambridge. This Fellowship enables me to further expand my research to develop effective treatments for patients with rare inherited neurological diseases.”

Professor Eric Miska FMedSci

Herchel Smith Chair of Molecular Genetics and Head of Department of Biochemistry, Affiliated Senior Group Leader at the Gurdon Institute, Associate Faculty at the Wellcome Sanger Institute and Fellow of St John’s College

Professor Miska is a molecular geneticist who has carried out pioneering work on RNA biology. His work led to fundamentally new insights into how small RNA molecules control our genes and protect organisms from selfish genes and viruses, and how RNA can carry heritable information across generations. Miska is Founder and Director of STORM Therapeutics Ltd, which creates novel therapies that inhibit RNA modifying enzymes for use in oncology and other diseases.

“Wonderful recognition of the work of an amazing team of researchers I have the pleasure to work with,” said Miska. “Most of our research has been done using the roundworm C. elegans. As Friedrich Nietzsche wrote in Thus Spoke Zarathustra: ‘You have evolved from worm to man, but much within you is still worm’.”

Professor Serena Nik-Zainal FMedSci

NIHR Research Professor, Professor of Genomic Medicine and Bioinformatics, Department of Medical Genetics and Early Cancer Institute, and Honorary Fellow of Murray Edwards College

Professor Nik-Zainal’s research is focused on investigating the vast number of mutations that occur in human DNA from birth, causing patterns called ‘mutational signatures’, and the associated physiological changes to cellular function, in progressive diseases such as cancer and neurodegeneration. She uses a combination of experimental and computational methods to understand biology and to develop clinical tests for early detection and precision diagnostics. Her team also builds computational tools to enable genomic advances become more accessible across the NHS.

“What an honour it is to be elected to the Fellowship. This is a wonderful recognition of the work from my team,” said Nik-Zainal. “We are thrilled and hugely indebted to all our inspiring collaborators, supporters and patients, who have shared in our passion and joined us on our path, exploring biomedical science and translating insights into patient benefit.”

Professor Julian Rayner FMedSci

Director of the Cambridge Institute for Medical Research, School of Clinical Medicine, Honorary Faculty at the Wellcome Sanger Institute, and Director of Wellcome Connecting Science

Professor Rayner’s research has made significant contributions to our understanding of how malaria parasites recognise and invade human red blood cells to cause disease. His work has helped to identify new vaccine targets, such as a protein essential for red blood cell invasion that is now in early stage human vaccine testing, and inform antimalarial drug development, through co-leading the first ever genome-scale functional screens in malaria parasites. He collaborates closely with researchers in malaria-endemic countries and is strongly committed to engaging public audiences with the process and outcomes of science.

“Malaria is a devastating and too often forgotten disease that still kills more than half a million children every year. Tackling it requires deep collaboration and working across disciplines. I’m enormously honoured by this announcement, which reflects not my work but the work of all the talented people I’ve been lucky enough to host in my lab, and collaborations with friends and colleagues across the world,” said Rayner.

“I’m excited to become a Fellow of the Academy of Medical Sciences because I strongly share their conviction that science is not just for scientists. I believe that dialogue, learning and public engagement are all fundamental and essential parts of the research process, and I look forward to contributing to their leading role in these areas.”

Professor James Rowe FMedSci

Professor of Cognitive Neurology, Department of Clinical Neurosciences, and MRC Cognition and Brain Sciences Unit

Professor Rowe leads a highly interdisciplinary research team at the Cambridge Centre for Frontotemporal Dementia and at Dementias Platform UK to improve the diagnosis and treatment of people affected by dementia. His work integrates cognitive neuroscience, brain imaging, fluidic biomarkers, computational models and neuropathology for experimental medicine studies and clinical trials. He is motivated by his busy clinical practice and the need for better diversity and inclusivity throughout medical research.

“I am delighted and honoured to be elected to the Fellowship of the Academy of Medical Sciences. It is a testament to the many wonderful colleagues and students I have been fortunate to work with, and to inspirational mentors,” said Rowe.

“Research excellence, and translation of research for direct human benefit, comes from innovation and collaboration in diverse cross-disciplinary teams. I believe in the vision and values of the Academy as the route to better health for all.”

In addition, two researchers from the wider community have also been elected:

Dr Trevor Lawley FMedSci, Senior Group Leader, Wellcome Sanger Institute and Chief Scientific Officer, Microbiotica

Professor Ben Lehner FRS FMedSci, Senior Group Leader, Human Genetics Programme, Wellcome Sanger Institute

Seven Cambridge ̽��ֱ�� researchers are among the 59 biomedical and health researchers elected to the Academy of Medical Sciences Fellowship.

As we look to the future, the collective wisdom our new Fellows bring will be pivotal in achieving our mission to create an open and progressive research sector to improve the health of people everywhere

Professor Dame Anne Johnson, President of the Academy of Medical Sciences

Clockwise from top left: E. Di Angelantonio, J. Rayner, J. Rowe, R. Horvath, S. Nik-Zainal, E. Miska, C. Coles

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

‘Super jelly’ can survive being run over by a car

sc604 — Thu, 25 Nov 2021 16:02:38 +0000

̽��ֱ��soft-yet-strong material, developed by a team at the ̽��ֱ�� of Cambridge, looks and feels like a squishy jelly, but acts like an ultra-hard, shatterproof glass when compressed, despite its high water content.

̽��ֱ��non-water portion of the material is a network of polymers held together by reversible on/off interactions that control the material’s mechanical properties. This is the first time that such significant resistance to compression has been incorporated into a soft material.

̽��ֱ��‘super jelly’ could be used for a wide range of potential applications, including soft robotics, bioelectronics or even as a cartilage replacement for biomedical use. ̽��ֱ��results are reported in the journal Nature Materials.

̽��ֱ��way materials behave – whether they’re soft or firm, brittle or strong – is dependent upon their molecular structure. Stretchy, rubber-like hydrogels have lots of interesting properties that make them a popular subject of research – such as their toughness and self-healing capabilities – but making hydrogels that can withstand being compressed without getting crushed is a challenge.

“In order to make materials with the mechanical properties we want, we use crosslinkers, where two molecules are joined through a chemical bond,” said Dr Zehuan Huang from the Yusuf Hamied Department of Chemistry, the study’s first author. “We use reversible crosslinkers to make soft and stretchy hydrogels, but making a hard and compressible hydrogel is difficult and designing a material with these properties is completely counterintuitive.”

Working in the lab of Professor Oren A Scherman, who led the research, the team used barrel-shaped molecules called cucurbiturils to make a hydrogel that can withstand compression. ̽��ֱ��cucurbituril is the crosslinking molecule that holds two guest molecules in its cavity – like a molecular handcuff. ̽��ֱ��researchers designed guest molecules that prefer to stay inside the cavity for longer than normal, which keeps the polymer network tightly linked, allowing for it to withstand compression.

“At 80% water content, you’d think it would burst apart like a water balloon, but it doesn’t: it stays intact and withstands huge compressive forces,” said Scherman, Director of the ̽��ֱ��’s Melville Laboratory for Polymer Synthesis. “ ̽��ֱ��properties of the hydrogel are seemingly at odds with each other.”

“ ̽��ֱ��way the hydrogel can withstand compression was surprising, it wasn’t like anything we’ve seen in hydrogels,” said co-author Dr Jade McCune, also from the Department of Chemistry. “We also found that the compressive strength could be easily controlled through simply changing the chemical structure of the guest molecule inside the handcuff.”

To make their glass-like hydrogels, the team chose specific guest molecules for the handcuff. Altering the molecular structure of guest molecules within the handcuff allowed the dynamics of the material to ‘slow down’ considerably, with the mechanical performance of the final hydrogel ranging from rubber-like to glass-like states.

“People have spent years making rubber-like hydrogels, but that’s just half of the picture,” said Scherman. “We’ve revisited traditional polymer physics and created a new class of materials that span the whole range of material properties from rubber-like to glass-like, completing the full picture.”

̽��ֱ��researchers used the material to make a hydrogel pressure sensor for real-time monitoring of human motions, including standing, walking and jumping.

“To the best of our knowledge, this is the first time that glass-like hydrogels have been made. We’re not just writing something new into the textbooks, which is really exciting, but we’re opening a new chapter in the area of high-performance soft materials,” said Huang.

Researchers from the Scherman lab are currently working to further develop these glass-like materials towards biomedical and bioelectronic applications in collaboration with experts from engineering and materials science. ̽��ֱ��research was funded in part by the Leverhulme Trust and a Marie Skłodowska-Curie Fellowship. Oren Scherman is a Fellow of Jesus College.

Reference:
Zehuan Huang et al. ‘Highly compressible glass-like supramolecular polymer networks.’ Nature Materials (2021). DOI: 10.1038/s41563-021-01124-x

Researchers have developed a jelly-like material that can withstand the equivalent of an elephant standing on it, and completely recover to its original shape, even though it’s 80% water.

At 80% water content, you’d think it would burst apart like a water balloon, but it doesn’t: it stays intact and withstands huge compressive forces

Oren Scherman

‘Super jelly’ can survive being run over by a car

Zehuan Huang

Super jelly

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

All things being equal

bjb42 — Thu, 27 May 2010 07:47:07 +0000

British employment legislation is anachronistic and out of sync with 21^st century parenting, says Jude Browne, Frankopan Director of the ̽��ֱ�� of Cambridge Centre for Gender Studies.

She is interested in how philosophical principles of inequality which underpin our laws translate into legislative practice, with a particular focus on gender equality.

Her talk at the Guardian Hay Festival will focus on the principle of equal treatment, which is a bedrock of EU equality policies. Investigating the principle throws up several interesting practicalities, such as how to think about the ways in which people should be treated more equally. Browne is interested in how current UK law seems to act against equality by forcing men and women into particular roles and denying them a full range of choice over how they conduct their family life.

She highlights legislation around maternity and paternity leave as a case in point. ̽��ֱ��inequality between women having months off work and men only having two weeks out of the workplace “herds people into traditional roles,” she says. “People have no choice unless they are very rich.”

This leads to all sorts of inequalities and potential discrimination in the workplace, with women of childbearing age viewed by some employers as a risky, expensive option, compared with men.

Browne says that the law should be about giving people the choice over how they wish to operate as a family unit, adding that the majority of households are now dual-earning. In many cases, both couples work full time and men want to be more involved in parenting.

She has little time for people who use generalisations to defend conservative legislation: “There is no single minded category,” she says. “I am very sceptical of assuming what people want. Men and women make decisions based on all sorts of factors. There are a whole range of scenarios.”

“ ̽��ֱ��law at present is very prescriptive about what men and women should be doing as parents and traps people into social norms despite the fact that attitudes have changed so much.”

Maternity legislation has undergone several changes in recent years; for instance, it was recently extended to one year in length. Browne says this is all very well and good if women want to take a year out, but in the absence of legislation allowing men to take similar time out for parenting duties, it might make a return to work for women more difficult and hence increase inequality in the workplace.

“There has to be a holistic approach to this issue,” says Browne. “ ̽��ֱ��legislation has to be properly thought through as it has a huge impact on the way people are able to organise their lives.”

Her talk fits with the multidisciplinary ethos of the ̽��ֱ�� of Cambridge Centre for Gender Studies. ̽��ֱ��idea is to bring together research and innovation on everything from law and philosophy to reproductive science and literature. One way the Centre is doing this is through a collaboration with the Guardian newspaper at the beginning of next term. They will jointly play host to three lectures on gender and the biomedical advances in the 21st century at the Guardian's offices in King's Place, London.

̽��ֱ��talks, which will be given by leading researchers aim to provide an open dialogue with the public so that they can understand the potential impact of scientific advances on society and their implications for gender.

Dr. Jude Browne will be speaking at the Hay Festival on June 6^th at 1pm.

UK law is different for men and women on issues such as maternity or paternity leave. Dr. Jude Browne’s research asks about whether our gender roles are being prescribed for us, and what needs to change in the interests of a more balanced and fair society.

Dennis from flickr

Ben's Crib

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Yes

Research sheds new light on why pancreatic cancer drugs fail

bjb42 — Thu, 21 May 2009 00:00:00 +0000

̽��ֱ��study, published in the journal Science today, shows that a genetically modified mouse model of pancreatic cancer, which closely resembles human cancer, is largely resistant to germcitabine treatment. It is hoped that these results will help scientists overcome a common resistance to germcitabine and make future chemotherapy drugs more effective.

̽��ֱ��scientists had set out to discover why promising drugs generally fail in pancreatic cancer clinical trials. They found that in these mice studies pancreatic cancer is resistant to chemotherapy because the tumours tend to have poor networks of blood vessels called vasculature, which makes it harder for drugs to reach the tumour.

Working with groups at Addenbrooke's Hospital, the Johns Hopkins Hospital, the ̽��ֱ�� of Dresden, MD Anderson Cancer Centre, ̽��ֱ�� of Pittsburgh and the Fred Hutchison Cancer Research Centre, they also noted that human pancreatic cancer samples also contained a deficient blood supply, suggesting that their observation should also be applicable to patients.

Senior author Dr David Tuveson, group leader in tumour modeling and experimental medicine at Cancer Research UK's Cambridge Research Institute, said: "We're extremely excited by these results as they may help explain the disappointing response that many pancreatic cancer patients receive from chemotherapy drugs."

̽��ֱ��study also found that the genetically modified mice displayed the same resistance to gemcitabine as seen in human pancreatic cancer, whereas the transplantation mouse models traditionally used to develop chemotherapy treatments were sensitive to gemcitabine. This means that the new genetically modified models could prove superior in developing new treatments in the future.

When the scientists added the compound called IPI-926, created by Infinity Pharmaceuticals, to gemcitabine, they noticed increased cell death and a reduction of the pancreatic tumour size. Using this combination the researcher believe that it could re-open the door to several new treatments which have, so far, proven disappointing in patient trials for pancreatic cancer because of poor drug delivery.

"But these are early days and we need to show this approach is safe to use in humans before we can consider adding the new compound to cancer treatments," said Dr Tuveson.

These findings may also help to explain why pancreatic cancer does not respond to anti-angiogenic drugs such as VEGF inhibitors when many other cancers do. These are a new class of drugs which starve the tumour by restricting its blood supply. As pancreatic cancers don't seem to need as good a supply of blood to the tumour as other cancers, the scientists believe that they may need to introduce additional drugs to help stop tumour growth.

̽��ֱ��scientists at Cancer Research UK's Cambridge Research Institute were co-funded by ̽��ֱ��Lustgarten Foundation and the National Institutes of Health.

̽��ֱ��Cancer Research UK Cambridge Research Institute is a major new research centre which aims to take the scientific strengths of Cambridge to practical application for the benefit of cancer patients. ̽��ֱ��Institute is a unique partnership between the ̽��ֱ�� of Cambridge and Cancer Research UK. It is housed in the Li Ka Shing Centre, a state-of-the-art research facility located on the Cambridge Biomedical Campus which was generously funded by Hutchison Whampoa Ltd, Cambridge ̽��ֱ��, Cancer Research UK, ̽��ֱ��Atlantic Philanthropies and a range of other donors. For more information visit www.cambridgecancer.org.uk.

An international team of scientists, led by researchers based at the Cambridge Research Institute, have discovered a new mechanism that may explain why pancreatic cancer patients are often resistant to a common chemotherapy treatment, germcitabine.

We're extremely excited by these results as they may help explain the disappointing response that many pancreatic cancer patients receive from chemotherapy drugs.

Dr David Tuveson

m.mate from Flickr

Blood

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Yes

Cambridge to host genetic research hub

bjb42 — Wed, 13 May 2009 00:00:00 +0000

̽��ֱ��MRC is investing over £7 million into supporting fundamental genetics research by creating three high-throughput sequencing (HTS) hubs in Scotland, the North of England and the East of England, giving every gene scientist across the UK access to cutting-edge equipment for DNA sequencing.

Cambridge is one of three 'hub' universities which have been given sufficient funds to purchase high-throughput sequencing machines that will enable the UK to retain its world-leading standing in DNA research. ̽��ֱ��hubs will also provide MRC-funded technical support and bioinformatics expertise that will allow academics to make the most of the equipment and expand the potential of these resources.

̽��ֱ��East of England hub will be hosted by the ̽��ֱ�� at the Cambridge Biomedical Campus, Addenbrooke's Hospital. It will be part of a collaboration with the European Molecular Biology Laboratory's European Bioinformatics Institute, the Babraham Institute, the NIHR Cambridge Biomedical Research Centre, and the next-generation sequencing technology companies 454 Life Sciences, a Roche company and Applied Biosystems, a division of Life Technologies Corporation.

Cambridge ̽��ֱ�� has a long and productive history in both the development and application of DNA sequencing technologies. ̽��ֱ��creation of the Eastern Sequencing and Informatics Hub, as it will be called, will enable researchers working in the region to utilise crucial 21st-century research technology in their studies.

In collaboration with the nearby European Bioinformatics Institute, an international centre for bioinformatics resources and data, including sequence data analysis, the Hub will provide researchers with access to all the tools required to analyse complicated datasets. It will have a focus on applying HTS to medical diagnostic uses, in particular in transplantation and cord blood stem cells, prenatal diagnosis, and re-sequencing of disease genes.

Professor John Todd, from the ̽��ֱ�� of Cambridge and one of the three hubs' Principal Investigators, said: " ̽��ֱ��development of even faster and less expensive ways of decoding genetic material and information, so called high throughput sequencing, is transforming our understanding of how organisms work, from bacteria to humans, and how certain diseases are strongly inherited. Only a few years ago, it took an international consortium many years of effort to produce a first draft of the human genome sequence, but now it will be possible for the proposed hub in Cambridge, the Eastern Sequence and Informatics Hub (EASIH), to re-sequence 100 human genomes in a year."

John Jeans, MRC Chief Operating Officer, said: "Though the fundamental science behind DNA sequencing has remained largely the same since Sanger's original work at the MRC Laboratory of Molecular Biology in the 1970s, the technology of DNA sequencing is revolutionising the field. This investment is key to retaining and enhancing the UK's competitiveness. It makes plain our commitment to supporting high quality basic research and exemplifies the responsiveness of MRC strategic investment to the needs of the research community."

John Jeans added: "Inviting regional applications has generated innovative partnerships between academic institutions, as well as engagement with industry, the NHS and Regional Genetics Services. This initiative will engender innovative ways of working and enable new and exciting discoveries. We hope the hubs will allow scientists to ask increasingly precise questions about diseases, and gather answers that were undreamt of only a decade ago."

̽��ֱ��MRC's £7 million investment was made by its Strategy Board in response to increasing numbers of grant applications requiring high-throughput sequencing. Having consulted widely with scientists, the Board called for proposals for regional hubs as this best met the needs of scientists and ensured the most optimal use of MRC funds across the genetics research community.

̽��ֱ�� ̽��ֱ�� of Cambridge will host one of just three genetic research hubs created by the Medical Research Council (MRC) to provide scientists access to cutting-edge resources for DNA sequencing.

Inviting regional applications has generated innovative partnerships between academic institutions, as well as engagement with industry, the NHS and Regional Genetics Services. This initiative will engender innovative ways of working and enable new and exciting discoveries.

John Jeans

Windy_ from Flickr

Nikon Microscope

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Yes

Cancer Research UK

bjb42 — Fri, 01 May 2009 00:00:00 +0000

Formed in 2002 by the amalgamation of the two largest UK cancer charities – the Cancer Research Campaign and the Imperial Cancer Research Fund – Cancer Research UK continues a century-long history of funding cancer research. Its annual research budget funds the work of over 4500 scientists, doctors and nurses across the UK, including research at a number of specialised institutes and centres. ̽��ֱ��most recent of the core-funded institutes, the Cambridge Research Institute (CRI), is a flagship research enterprise located on the Cambridge Biomedical Campus.

In 2007–8, Cancer Research UK spent just over £31.5 million on laboratory research and clinical trials in Cambridge; around £17.5 million of this annual research spend provided core funding for the CRI.

Funding by Cancer Research UK covers all aspects of cancer research, from understanding fundamental cancer cell biology to large epidemiology studies across entire populations of people, as well as training the next generation of research scientists. Some examples in Cambridge include:

Several programme grants and a significant element of core funding to the Wellcome Trust/Cancer Research UK Gurdon Institute, where research is helping to uncover what goes wrong when a cell becomes cancerous, by investigating the processes that ensure that cells function correctly during normal development.
Funding the two UK arms of the largest study of diet and health ever undertaken – the European Prospective Investigation into Cancer and Nutrition (EPIC) – a long-term study of more than half a million people in 10 European countries. ̽��ֱ�� ̽��ֱ�� of Cambridge manages the Norfolk arm of EPIC, which has recruited more than 30,000 people.
Scientists at the Strangeways Research Laboratory and Department of Oncology, who are searching for genes that increase cancer risk and investigating how the effects of the genes combine with lifestyle factors to cause cancer.
Cancer Research UK PhD Training Programme in Medicinal Chemistry, a collaborative initiative that brings together research groups with expertise in synthesis chemistry, pharmacology, biochemistry and cancer biology to train synthesis chemists to PhD level.

For more information, please visitwww.cancerresearchuk.org

Cancer Research UK is the world's leading independent charity dedicated to cancer research, spending around £300 million a year on world-class research to beat cancer. In November 2008, the charity launched a five-year plan to focus research on core areas of science that will have the greatest impact on reducing cancer deaths, with an emphasis on cancers that have poor survival rates.

GE healthcare from Flickr

Kyung Chae Jeong, National Cancer Center, South Korea

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Yes

Putting metabolism on the eco-map

tdk25 — Fri, 01 Feb 2008 00:00:00 +0000

To what extent do living organisms absorb pollutants in our environment? Are particular ‘chemical cocktails’ more risky than others? Do current ecotoxicological risk assessment techniques adequately protect the environment? These are the sorts of questions that interest Drs Oliver Jones and Julian Griffin in the Department of Biochemistry, who are working as part of a Europe-wide integrated research project to develop better tools to evaluate the chemical risks we face in everyday life.

Ecotoxicology

It is generally acknowledged that many organisms in the environment are exposed to a large variety of pollutants during their lifetime; a fact borne out by advances in analytical technology. For example, many people will have heard of the effects on fish populations caused by endocrine-disrupting compounds in sewage, whereby some male fish living downstream of sewage treatment plants were found to have developed female characteristics, leading to a reduction in their ability to reproduce. In recent years, a plethora of other anthropogenic contaminants such as pharmaceuticals, personal care products, pesticides and flame retardants, and the potential for these man-made products to work their way into the food chain, have also begun to be of concern to environmental chemists.

However, the majority of these pollutants are present at extremely low concentrations and so it is difficult to ascertain whether or not they have an overall effect on ecosystem health, especially if outward effects are minimal. An added complication is the fact that the interaction between the environment and organism health is extremely complex, with chemical, biological, physical and geographical stressors each contributing to toxicological effects over time.

It’s important therefore to develop methods for assessing the cumulative risks for a range of species that are being exposed to mixtures of pollutants at non-lethal levels. In this way, steps can be taken both to improve safety in the environment and to safeguard ecological health.

Metabolomics

One technique that shows a great deal of promise in the area of ecotoxicology is metabolomics. This rapidly emerging discipline measures the thousands of naturally occurring small molecules (metabolites) such as sugars, organic acids, amino acids and lipids that are the products of cellular metabolism. An organism’s ‘metabolome’ is its full complement of metabolites, in the same way that its genome is its complete genetic content.

Why study metabolic changes? Well, these changes often happen much earlier in an organism than either tissue accumulation of pollutants or induced histopathological changes. ̽��ֱ��technique can be used to give a biochemical snapshot of a cell, tissue or indeed whole organism at a moment in time. When an organism is stressed or diseased, its metabolic pathways are perturbed. Advanced computer-assisted pattern recognition techniques can then be used to assess the differences in metabolic profiles between sample groups. Metabolomics therefore offers a particularly sensitive method to monitor changes in a biological system and is proving to be an outstanding tool for studying ecotoxicology.

No Miracle

̽��ֱ��environmental research in Dr Griffin’s group in the Department of Biochemistry is part of a European Union (EU) research project involving 38 laboratories spread across 16 countries and is known as NoMiracle (for ‘Novel Methods for Integrated Risk Assessment of Cumulative Stressors in Europe’). ̽��ֱ��project seeks to improve ecological and environmental risk assessment in the EU, and to help scientists gauge the impact of chemicals on the environment and human health.

̽��ֱ��Cambridge team are developing analytical techniques based on high-throughput analysis of metabolites from organisms at different positions in the food chain, such as earthworms, nematodes, slime moulds, marine mussels and water fleas. Being able to study such a broad set of experimental species has been possible because of long-term collaborations with the Centre for Ecology and Hydrology (part of the UK Natural Environment Research Council), King’s College London, the ̽��ֱ�� of Piemonte Orientale in Italy and the ̽��ֱ�� of Antwerp in Belgium, all developed as part of the NoMiracle project.

Using state-of-the-art nuclear magnetic resonance spectroscopy and gas chromatography mass spectrometry, long-term studies are being run to establish a basal metabolic profile for each of these species, as well as how these profiles change in response to toxic insult. By looking at the different patterns of metabolic profiles between organisms, a comprehensive description is being built up of how each of them responds to stress and toxicity. One important finding has been that biochemical effects are often observed at lower chemical concentrations than were previously thought to cause any effect when assessed using traditional toxicology testing techniques.

Assessing the risks

Why is there a need for improved risk assessment in ecotoxicology? In current toxicity tests, an organism is typically exposed to a single chemical in a strictly controlled laboratory setting, over a relatively short period of time (typically days or weeks). Yet, in the environment, organisms will clearly be exposed to many different pollutants possibly throughout their entire life. An accurate risk assessment must take into account cumulative effects rather than just direct effects and single factors. Organisms are also often likely to be stressed by other factors not present in a laboratory setting. For instance, work within the NoMiracle project has demonstrated that organisms can be affected by pollutants at much lower levels than those predicted from traditional toxicity tests if they are also stressed by other factors such as co-exposure to pollutants, temperature extremes or food restriction.

̽��ֱ��work in the Cambridge section of the NoMiracle project is moving into its third and final year. ̽��ֱ��research is showing that the accurate assessment of chemical mixtures is more complex than current testing regimes allow for and the aim now is to use these results to develop a new framework for assessing the effects of complex mixtures of pollutants. ̽��ֱ��ultimate goal of the NoMiracle partners is to change ecotoxicology policy in the whole of the EU, so that long-term, multi-stressor exposure testing is considered as standard. This will offer great improvements in understanding and mitigating the effects of cumulative pollution exposure on the health of our ecosystem.

For more information, please contact the authors Dr Oliver Jones (oahj2@mole.bio.cam.ac.uk) or Dr Julian Griffin (jlg40@mole.bio.cam.ac.uk) at the Department of Biochemistry.

One of the latest technologies to emerge - metabolomics - is being used to create a snapshot of how environmental chemicals affect living organisms.

An added complication is the fact that the interaction between the environment and organism health is extremely complex, with chemical, biological, physical and geographical stressors each contributing to toxicological effects over time.

Karolina Lada and Oliver-Jones

Tricarboxylic Acid (TCA) Cycle

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Parasites: the master manipulators

tdk25 — Sat, 01 Sep 2007 00:00:00 +0000

̽��ֱ��human race used to have a consensus attitude towards the organisms that we call parasites. They were simply pests, causative agents of disease that warranted nothing else other than extermination. As soon as new life-cycles were described in the literature, the race began to find a way of interrupting transmission and end the misery. ̽��ֱ��literature is therefore full of examples of control programmes for just about every parasite that has ever been identified. Some, such as the programme against the guinea worm, Dracunculus medinensis, have been so successful that complete eradication is now on the World Health Organization’s agenda.

As we wave goodbye to the guinea worm, it will be time to re-visit the hit-list, and to see how far we’ve progressed. In doing so, we are likely to observe that not much has changed. In fact, the guinea worm is the only parasitic infection that has ever been described and then systematically eradicated. There are even signs that the parasitic fauna of the planet is flourishing – recent estimates put the toll of malaria at between 300 and 660 million cases a year, and there are still hundreds of millions of people infected by each of several parasitic worm species. This group includes the trematode parasite Schistosoma mansoni – a blood fluke that infects approximately 200 million people in the tropics and sub-tropics, and which has been the focus of research efforts at the ̽��ֱ�� of Cambridge Department of Pathology for the past 30 years.

Fighting the fluke

Theodor Bilharz formally described schistosome parasites in 1851, at which point the centimetre-long, red-blood-cell-eating worm joined the most-wanted list. Like every other parasitic infection, S. mansoni was viewed with fear and loathing – and with good reason. Infection occurs through contact with free-living larvae in freshwater, with rapid penetration of intact human skin. ̽��ֱ��adults live in the mesenteric veins between the liver and gut. Females produce eggs that become trapped in the liver, promoting an inflammatory response that eventually leads to a form of hepatic fibrosis and portal hypertension. About half the eggs pass through the gut wall, each puncture causing a small amount of blood to be lost. As the worm burden increases with repeated exposure, so the number of eggs in both the liver and gut increases, leading to ever more severe disease.

Early attempts at large-scale control of schistosome infections relied on crude drugs and environmental modification, with success in some areas, but in most places the parasite persisted. Although treatment (praziquantel) is available, re-infection occurs rapidly, especially in children. ̽��ֱ��lack of effective, non-toxic medicine, and the success of vaccination programmes against bacterial diseases, led to the emergence of renewed research efforts aimed at understanding the biology of the worm and its relationship with the human host.

But, despite promises of an anti-schistosome vaccine ‘within five years’ for the past 20 years or so, there is still no vaccine available, because we don’t yet understand the biology of the schistosome worm. Like a fractal puzzle, as we peer more closely we see even greater complexity.

Keeping things quiet

Such is the intimate relationship between host and parasite that we can use the study of schistosome parasites to understand how humans work. One of the key questions that has kept scientists busy is how schistosomes manage to evade the immune response for extended periods. It has been estimated that adult worms live for up to 10 years in their human host. To make this possible, the worms have evolved several mechanisms for diverting, blocking and repressing the immune response. ̽��ֱ��adult worms coat themselves in host proteins to appear invisible to the immune system. They induce the host to produce ineffective immune responses and they manipulate host cells to produce molecules that signal a general downregulation of the host’s response. This essentially produces a drowsy immune response with impaired vision against a camouflaged target – perfect conditions for the parasite to thrive and reproduce

Recent studies in Cambridge in the laboratory of Professor David Dunne have demonstrated the magnitude of this repressive effect by treating people who are already infected with the parasite and measuring their immune responses before and after taking praziquantel. Responses that are thought to be effective against the parasite often increase several fold after drug treatment, and this ‘boosting’ of the host’s ability to respond appears to help prevent re-infection in the future. Recently, the scientists also reported that the ability to respond after treatment is genetically restricted – an observation that has important implications for the development of any therapy or vaccine that relies on increasing the magnitude of the immune response for its protective effect.

Medical benefits

Although a vaccine is not yet in sight, recent discoveries have raised an interesting conundrum: rather than simply being agents of disease, it appears that parasitic infections, including schistosome worms, may bring medical benefits. Scientists in Cambridge are leading the field in efforts to find out just what is going on.

As more knowledge of the host–parasite relationship is gained, it is becoming increasingly clear that parasitic infections are not necessarily pests that need to be eradicated. Nobody used to have any sympathy for leeches or maggots, but both creatures are now used in medical settings: leeches to clear blood from congested tissues after surgery, and maggots to liquefy dead tissue and kill harmful bacteria in infected wounds. ̽��ֱ��same thing is now happening to parasites, as it emerges that their influence on the immune system can benefit both host and parasite.

In the Department of Pathology, a clear example of this win–win scenario was demonstrated when researchers in Professor Anne Cooke’s group prevented type 1 diabetes from developing in mice by injecting them with antigens of schistosome parasites. This is likely to be due to the same skewing and downregulation of the host immune response described above.

It seems that by diverting and subverting the immune response, schistosome parasites may prevent the immune system from over-reacting to other proteins. One hypothesis gaining popularity is that, when parasites are removed, the immune response finds new targets, either in harmless allergens (leading to allergy), or in the host itself (leading to autoimmune diseases such as type 1 diabetes).

With such tantalising evidence, it may be time to look at the parasite hit-list with fresh eyes, and ask: can we exploit the intimate relationship parasites have with humans at the same time as reducing their tremendous burden on affected populations?

̽��ֱ��Matangini Project

̽��ֱ��Matangini Project was created by Dr Mark Booth, in the Schistosomiasis Research Group at the Department of Pathology, to raise funds for community projects in Kenya and Uganda. ̽��ֱ��aim in 2007 is to raise £5000 to bring safe water to thousands of school children in areas of Kenya affected alternately by drought and water-borne infections such as schistosomiasis.

Cambridge Infectious Disease Initiative

̽��ֱ�� ̽��ֱ�� of Cambridge is currently developing a major Infectious Disease Initiative, with the aim of increasing the ̽��ֱ��’s contribution to reducing the global impact of infectious diseases. By building new partnerships based on core strengths, the vision is to establish the ̽��ֱ�� as a leading international centre for infectious disease teaching and research.

For further information, please contact the Co-ordinator Dr Gill Rands (gfr21@cam.ac.uk).

For more information, please contact the author Dr Mark Booth (mb350@cam.ac.uk) at the Department of Pathology (www.path.cam.ac.uk/~schisto).

̽��ֱ��common view has been that parasitic infections cause disease and must be eliminated. But can we live without them?

As more knowledge of the host–parasite relationship is gained, it is becoming increasingly clear that parasitic infections are not necessarily pests that need to be eradicated.

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Flatworm

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