̽��ֱ�� of Cambridge - EMBO

Cambridge scientists elected as Members of the European Molecular Biology Organisation

jg533 — Tue, 09 Jul 2024 12:00:56 +0000

Five Cambridge researchers join the community of over 2,100 leading life scientists today as the European Molecular Biology Organisation (EMBO) announces its newest Members in its 60th anniversary year.

Cambridge researchers elected as members of European Molecular Biology Organisation

cjb250 — Wed, 06 Jul 2022 12:00:22 +0000

Five Cambridge researchers join the community of more than 1,900 leading life scientists in Europe and beyond today as the European Molecular Biology Organisation announces its newly-elected Members.

Eight Cambridge researchers elected as members of the European Molecular Biology Organisation

Anonymous — Tue, 07 Jul 2020 13:00:56 +0000

EMBO Membership honours distinguished scientists who have made outstanding contributions to the life sciences, including 88 Nobel Laureates. It is an international organisation of life scientists, which has more than 1800 members elected by peers.

̽��ֱ��newly elected Cambridge researchers are:

Professor Bertie Göttgens, Professor of Molecular Haematology, Deputy Director of the Wellcome MRC Stem Cell Institute, and a member of the Cancer Research UK (CRUK) Cambridge Centre Haematological Malignancies Programme. Bertie’s research group studies how transcription factor networks control the function of blood stem cells, and how mutations that perturb these networks cause leukaemia.

Göttgens said:"This honour is very much a reflection of the dedicated work and collective effort of all members of my research group over the years. Rather fittingly, I kick-started my independent career with a paper in an EMBO Journal. Becoming an EMBO member therefore represents a very special milestone to me."

Professor Kathryn Lilley, Director of the Cambridge Centre for Proteomics, Department of Biochemistry, Milner Therapeutics Institute, and a member of the CRUK Cambridge Centre Cell and Molecular Biology Programme. Kathryn’s research aims to interrogate how the functional proteome correlates with complexity.

Lilley said: “I feel extremely honoured to have been elected as a member of EMBO by my peers, which also recognizes the efforts and achievements on my fabulous research group members and numerous collaborators both past and present.”

Dr Serena Nik-Zainal, a CRUK Advanced Clinician Scientist at the ̽��ֱ��’s MRC Cancer Unit, and Honorary Consultant in Clinical Genetics at Addenbrooke’s Hospital. Serena’s research combines computational and experimental approaches to understand cellular changes and mutational processes that lead to cancer and age-related disorders.

Nik-Zainal said: “It’s a great honour to become a member of EMBO, opening up opportunities for exploring new interactions with colleagues through Europe and around the world.”

Professor Giles Oldroyd FRS, Russell R Geiger Professor of Crop Science at the Sainsbury Laboratory and Director of the Crop Science Centre. Giles is leading an international programme of research that attempts to achieve more equitable and sustainable agriculture through the enhanced use of beneficial microbial associations.

Oldroyd said: “I have long admired the work that EMBO does to strengthen and coordinate science across Europe and it is an honour to now be a part of this prestigious European fellowship of biologists.”

Professor Uta Paszkowski, Professor of Plant Molecular Genetics at the Department of Plant Sciences. Uta leads the Cereal Symbiosis Group, which investigates the molecular mechanisms underlying formation and functioning of arbuscular mycorrhizal symbioses (beneficial interactions between roots of land plants and soil fungi) in rice and maize.

Paszkowski said: “Across the organisations supporting the Life Sciences, EMBO stands out by its varied activities to advance science through facilitating knowledge exchange and career development. I am immensely honoured to be elected as a member.”

Professor Anna Philpott, Head of the School of Biological Sciences, Professor of Cancer and Developmental Biology, and member of the CRUK Cambridge Centre Paediatric Cancer Programme. Anna’s research group at the Wellcome-MRC Cambridge Stem Cell Institute studies the balance between proliferation and differentiation during development and cancer, using a range of models.

Philpott said: “I am delighted to be invited to join an organisation that has done so much for European science.”

Dr Chris Tate, research leader at the MRC Laboratory of Molecular Biology. ̽��ֱ��research in Chris’ lab focusses on understanding the structure and function of the major cell-surface receptors in humans that are targeted by 34% of marketed small molecule drugs.

Tate said: “ ̽��ֱ��election to EMBO Membership is a great honour and will enhance my interactions with the superb scientists throughout Europe. ̽��ֱ��strength of the scientific community in Europe is amazing and we all benefit enormously from being a member of this family.”

Dr Marta Zlatic, research leader at the MRC Laboratory of Molecular Biology. Marta’s lab combines connectomics with physiology and behavioural analysis, in the tractable Drosophila larval model system, to discover the fundamental principles by which brains generate behaviour.

Zlatic said: "I feel extremely honoured and grateful that our research is being recognized in this way."

EMBO Members can actively participate in EMBO’s initiatives by serving on the organisation's Council, committees and editorial boards, participating in the evaluation of applications for EMBO funding, acting as mentors to young scientists in the EMBO community, and advising on key activities. EMBO’s administrative headquarters are in Heidelberg, Germany.

Eight Cambridge researchers - six from the ̽��ֱ�� of Cambridge and two from the MRC Laboratory of Molecular Biology - are among the 63 scientists from around the world elected this year as Members and Associate Members of the European Molecular Biology Organisation (EMBO).

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Cambridge scientists recognised by major European research organisation

cjb250 — Tue, 18 Jun 2019 11:42:19 +0000

Cambridge ̽��ֱ�� has the highest number of new members of any institution within Europe. Five ̽��ֱ�� of Cambridge researchers are among the 48 scientists from 17 countries elected:

Professor Sadaf Farooqi – Wellcome-Medical Research Council (MRC) Institute of Metabolic Science
Dr Fanni Gergely – Cancer Research UK Cambridge Institute
Professor Paul Lehner – Department of Medicine and the Cambridge Institute for Medical Research
Professor Lalita Ramakrishnan – Department of Medicine and the MRC Laboratory of Molecular Biology
Professor Nicole Soranzo – Department of Haematology and Wellcome Sanger Institute

In addition, Dr Garib Murshudov from the MRC Laboratory of Molecular Biology has also been elected.

EMBO is an organisation of more than 1800 leading researchers in Europe and around the world, whose mission is to promote excellence in the life sciences in Europe and beyond. ̽��ֱ��major goals of the organisation are to support talented researchers at all stages of their careers, stimulate the exchange of scientific information and help build a research environment where scientists can achieve their best work.

“EMBO Members are excellent scientists who conduct research at the forefront of all life science disciplines, ranging from computational models or analyses of single molecules and cellular mechanics to the study of higher-order systems in development, cognitive neuroscience and evolution,” says EMBO Director Maria Leptin.

“We’re very honoured to have been elected as members of EMBO,” says Professor Farooqi. “This is great recognition for the excellent science taking place across our city, particularly on the Cambridge Biomedical Campus. We are proud of the role we play in European science and look forward to continuing to work in partnership with colleagues across the continent.”

Researchers from the Cambridge Biomedical Campus have featured prominently in this year’s election to the prestigious European Molecular Biology Organisation (EMBO).

We are proud of the role we play in European science and look forward to continuing to work in partnership with colleagues across the continent

Sadaf Farooqi

CDC/ Melissa Brower

This illustration depicts a three-dimensional (3D) computer-generated image of a cluster of rod-shaped drug-resistant Mycobacterium tuberculosis bacteria, the pathogen responsible for causing the disease tuberculosis (TB).

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Quadruple helix form of DNA may aid in the development of targeted cancer therapies

sc604 — Mon, 12 Sep 2016 15:00:01 +0000

Scientists have identified where a four-stranded version of DNA exists within the genome of human cells, and suggest that it may hold a key to developing new, targeted therapies for cancer.

In work funded by Cancer Research UK and EMBO, the researchers, from the ̽��ֱ�� of Cambridge, found that these quadruple helix structures occur in the regions of DNA that control genes, particularly cancer genes, suggesting that they may play a role in switching genes on or off. ̽��ֱ��results, reported in the journal Nature Genetics, could also have implications for cancer diagnostics and the development of new targeted treatments.

Most of us are familiar with the double helix structure of DNA, but there is also a version of the molecule which has a quadruple helix structure. These structures are often referred to as G-quadruplexes, as they form in the regions of DNA that are rich in the building block guanine, usually abbreviated to ‘G’. These structures were first found to exist in human cells by the same team behind the current research, but at the time it was not exactly clear where these structures were found in the genome, and what their role was, although it was suspected that they had a link with certain cancer genes.

“There have been a number of different connections made between these structures and cancer, but these have been largely hypothetical,” said Professor Shankar Balasubramanian, from Cambridge’s Department of Chemistry and Cancer Research UK Cambridge Institute, and the paper’s senior author. “But what we’ve found is that even in non-cancer cells, these structures seem to come and go in a way that’s linked to genes being switched on or off.”

Starting with a pre-cancerous human cell line, the researchers used small molecules to change the state of the cells in order to observe where the G-quadruplexes might appear. They detected approximately 10,000 G-quadruplexes, primarily in regions of DNA associated with switching genes on or off, and particularly in genes associated with cancer.

“What we observed is that the presence of G-quadruplexes goes hand in hand with the output of the associated gene,” said Balasubramanian. This suggests that G-quadruplexes may play a similar role to epigenetic marks: small chemical modifications which affect how the DNA sequence is interpreted and control how certain genes are switched on or off.

̽��ֱ��results also suggest that G-quadruplexes hold potential as a molecular target for early cancer diagnosis and treatment, in particular for so-called small molecule treatments which target cancer cells, instead of traditional treatments which hit all cells.

“We’ve been looking for an explanation for why it is that certain cancer cells are more sensitive to small molecules that target G-quadruplexes than non-cancer cells,” said Balasubramanian. “One simple reason could be that there are more of these G-quadruplex structures in pre-cancerous or cancer cells, so there are more targets for small molecules, and so the cancer cells tend to be more sensitive to this sort of intervention than non-cancer cells.

“It all points in a certain direction, and suggests that there’s a rationale for the selective targeting of cancer cells.”

“We found that G-quadruplexes appear in regions of the genome where proteins such as transcription factors control cell fate and function,” said Dr Robert Hänsel-Hertsch, the paper’s lead author. “ ̽��ֱ��finding that these structures may help regulate the way that information is encoded and decoded in the genome will change the way we think this process works.”

Dr Emma Smith, Cancer Research UK’s science information manager, said: “Figuring out the fundamental processes that cancer cells use to switch genes on and off could help scientists develop new treatments that work against many types of the disease. And exploiting weaknesses in cancer cells could mean this approach would cause less damage to healthy cells, reducing potential side effects. It’s still early days, but promising leads like this are where the treatments of the future will come from.”

Reference:
Robert Hänsel-Hertsch et. al. ‘G-quadruplex structures mark human regulatory chromatin.’ Nature Genetics (2016). DOI: 10.1038/ng.3662

Researchers have identified the role that a four-stranded version of DNA may play in the role of cancer progression, and suggest that it may be used to develop new targeted cancer therapies.

It all points in a certain direction, and suggests that there’s a rationale for the selective targeting of cancer cells.

Shankar Balasubramanian

Thomas Splettstoesser

Crystal structure of parallel quadruplexes from human telomeric DNA.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Cancer-associated DNA changes exist in a quarter of normal skin cells

cjb250 — Thu, 21 May 2015 18:00:39 +0000

̽��ֱ��study revealed that each cell in normal facial skin carries many thousands of mutations, mainly caused by exposure to sunlight. Around one in four skin cells in samples from people without cancer were found to carry at least one cancer-associated mutation.

Ultra-deep genetic sequencing was performed on 234 biopsies taken from four patients revealing 3,760 mutations, with more than 100 cancer-associated mutations per square centimetre of skin. Cells with these mutations formed clusters of cells, known as clones, that had grown to be around twice the size of normal clones, but none of them had become cancerous.

“With this technology, we can now peer into the first steps a cell takes to become cancerous,” explains Dr Peter Campbell, a corresponding author from the Wellcome Trust Sanger Institute. “These first cancer-associated mutations give cells a boost compared to their normal neighbours. They have a burst of growth that increases the pool of cells waiting for the next mutation to push them even further. We can even see some cells in normal skin that have taken two or three such steps towards cancer. How many of these steps are needed to become fully cancerous? Maybe five, maybe 10, we don’t know yet.”

̽��ֱ��mutations observed showed the patterns associated with the most common and treatable form of skin cancer linked to sun exposure, known as cutaneous squamous cell carcinoma, rather than melanoma, a rarer and sometimes fatal form of skin cancer.

“ ̽��ֱ��burden of mutations observed is high but almost certainly none of these clones would have developed into skin cancer,” says Dr Iñigo Martincorena, first author from the Sanger Institute. “Because skin cancers are so common in the population, it makes sense that individuals would carry a large number of mutations. What we are seeing here are the hidden depths of the iceberg, not just the relatively small number that break through the surface waters to become cancer.”

Skin samples used in this study were taken from four people aged between 55 and 73 who were undergoing routine surgery to remove excess eyelid skin that was obscuring vision. ̽��ֱ��mutations had accumulated over each individual’s lifetime as the eyelids were exposed to sunshine. ̽��ֱ��researchers estimate that each sun-exposed skin cell accumulated on average a new mutation in its genome for nearly every day of life.

“These kinds of mutations accumulate over time – whenever our skin is exposed to sunlight, we are at risk of adding to them,” explains Dr Phil Jones, a corresponding author from the Sanger Institute and the MRC Cancer Unit at the ̽��ֱ�� of Cambridge. “Throughout our lives we need to protect our skin by using sun-block lotions, staying away from midday sun and covering exposed skin wherever possible. These precautions are important at any stage of life but particularly in children, who are busy growing new skin, and older people, who have already built up an array of mutations.”

Recent studies analysing blood samples from people who do not have cancer had revealed a lower burden of mutations, with only a small percentage of individuals carrying a cancer-causing mutation in their blood cells. Owing to sun exposure, skin is much more heavily mutated, with thousands of cancer-associated mutations expected in any adult’s skin.

̽��ֱ��research was primarily supported by the Wellcome Trust, the Medical Research Council, Cancer Research UK and EMBO.

Adapted from a press release from the Wellcome Trust Sanger Institute

Reference
Martincorena I, et al. (2015). High burden and pervasive positive selection of somatic mutations in normal human skin. Science.

Normal skin contains an unexpectedly high number of cancer-associated mutations, according to a study published in Science. ̽��ֱ��findings illuminate the first steps cells take towards becoming a cancer and demonstrate the value of analysing normal tissue to learn more about the origins of the disease.

These kinds of mutations accumulate over time – whenever our skin is exposed to sunlight, we are at risk of adding to them

Phil Jones

What can healthy skin teach us about skin cancer?

Julie Jordan Scott

'Skin cancer selfies' (cropped)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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'Remodelling' damaged nuclei could lead to new treatments for accelerated ageing disease

cjb250 — Thu, 01 May 2014 18:00:00 +0000

Around 150 people worldwide are known to suffer from HGPS, a disease which results from a specific genetic mutation which is not inherited. Usually diagnosed around the age of six months, children with HGPS lose their hair, look old and suffer many of the symptoms of ageing, including brittle bones, stroke and heart attacks. They generally live only until their early teens.

In cells from people with HGPS, the nucleus is marked out because, unlike a normal cell’s round nucleus, HGPS cell nuclei are drastically misshapen. Scientists believe this makes the cells more fragile, contributing to HGPS patients’ symptoms.

Proteins called Lamin A and Lamin C play a vital role in nuclear architecture, acting as ‘scaffolding’ for the nucleus. In HGPS, however, mutations in the gene that makes these proteins mean they cannot shape the nucleus correctly.

Working with cells from HGPS patients, researchers from the Wellcome Trust/CRUK Gurdon Institute at the ̽��ֱ�� of Cambridge and the CNRS in France scoured the scientific literature for compounds that might affect nuclear architecture. They then tested a shortlist of the most promising compounds on the cells in the laboratory. Their results are published in the journal Science.

They found that one compound – which they were able to improve, yielding a molecule that they have named Remodelin – effectively improved the damaged nuclei, restoring their shape. Further tests revealed that doing so also improved the health of the cells, making them grow and divide more normally.

̽��ֱ��researchers then went on a ‘fishing trip’ to try to work out how the compound worked. According to Dr Delphine Larrieu of the Gurdon Institute, lead author of the study, “Most drugs work by binding to something in the cell, so we went fishing. We attached a chemical ‘hook’ to Remodelin, incubated it with cell extracts, and examined what was attached to it when we reeled it back in.

̽��ֱ��target they fished out was NAT10, a protein not previously associated with ageing or HPGS. “From our following work, we now know that Remodelin works by inhibiting NAT10, so we have gone from finding a potential drug to identifying its target and mechanism-of-action,” she said.

̽��ֱ��results are exciting because few drugs are available to treat HGPS (those that are available only partially improve some of the symptoms and do not extend people’s life span) and because Remodelin works in a different way. Senior author Professor Steve Jackson says: “Remodelin is different because as well as improving the cellular defects, it is the first molecule to also reduce the high level of DNA damage that occurs in these cells, which is believed to contribute to premature ageing. What we’re particularly excited about is that Remodelin seems to work in a different way from existing drugs, and has broader effects.”

These findings also improve our understanding of normal ageing, because although HGPS is very rare and devastating, it shares many features with normal ageing. Moreover, this could open up new treatments for some forms of cancer, because up- or down-regulation of nuclear-lamina proteins has been linked to the aggressiveness of certain cancers.

“This is an example of how basic cell biology can give rise to potential new opportunities for treating human disease, and although our research is focused on one rare disease, we feel that similar approaches could be useful in identifying new treatments for other serious human diseases,” he said.

̽��ֱ��next stage of the research, which is already underway, is to see if Remodelin works in animal models of the disease; if it does, the researchers will be able to trial the drug in patients.

̽��ֱ��research was supported by EMBO, Cancer Research UK, the Wellcome Trust and the Medical Research Council.

Scientists at the ̽��ֱ�� of Cambridge have identified a key chemical that can repair the damage to cells which causes a rare but devastating disease involving accelerated ageing. As well as offering a promising new way of treating the condition, known as Hutchinson-Gilford Progeria Syndrome (HGPS), the discovery could help in the development of drugs against cancer and other genetic diseases and might also suggest ways to alleviate diseases that we associate with normal ageing.

We have gone from finding a potential drug to identifying its target and mechanism-of-action

Delphine Larrieu

Cell nucleus before (left) and after (right) treatment with Remodelin

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