̽��ֱ�� of Cambridge - Wellcome Sanger Institute

Early career researchers win major European funding

ta385 — Thu, 05 Sep 2024 09:30:00 +0000

Of 3,500 proposals reviewed by the ERC, only 14% were selected for funding – Cambridge has the highest number of grants of any UK institution.

ERC Starting Grants – totalling nearly €780 million – support cutting-edge research in a wide range of fields, from life sciences and physics to social sciences and humanities.

̽��ֱ��awards help researchers at the beginning of their careers to launch their own projects, form their teams and pursue their most promising ideas. Starting Grants amount to €1.5 million per grant for a period of five years but additional funds can be made available.

In total, the grants are estimated to create 3,160 jobs for postdoctoral fellows, PhD students and other staff at host institutions.

Cambridge’s recipients work in a wide range of fields including plant sciences, mathematics and medicine. They are among 494 laureates who will be leading projects at universities and research centres in 24 EU Member States and associated countries. This year, the UK has received grants for 50 projects, Germany 98, France 49, and the Netherlands 51.

Cambridge’s grant recipients for 2024 are:

Adrian Baez-Ortega (Dept. of Veterinary Medicine, Wellcome Sanger Institute) for Exploring the mechanisms of long-term tumour evolution and genomic instability in marine transmissible cancers

Claudia Bonfio (MRC Laboratory of Molecular Biology) for Lipid Diversity at the Onset of Life

Tom Gur (Dept. of Computer Science and Technology) for Sublinear Quantum Computation

Leonie Luginbuehl (Dept. of Plant Sciences) for Harnessing mechanisms for plant carbon delivery to symbiotic soil fungi for sustainable food production

Julian Sahasrabudhe (Dept. of Pure Mathematics and Mathematical Statistics) for High Dimensional Probability and Combinatorics

Richard Timms (Cambridge Institute for Therapeutic Immunology and Infectious Disease) for Deciphering the regulatory logic of the ubiquitin system

Hannah Übler (Dept. of Physics) for Active galactic nuclei and Population III stars in early galaxies

Julian Willis (Yusuf Hamied Department of Chemistry) for Studying viral protein-primed DNA replication to develop new gene editing technologies

Federica Gigante (Faculty of History) for Unveiling Networks: Slavery and the European Encounter with Islamic Material Culture (1580– 1700) – Grant hosted by the ̽��ֱ�� of Oxford

Professor Sir John Aston FRS, Pro-Vice-Chancellor for Research at the ̽��ֱ�� of Cambridge, said:

“Many congratulations to the recipients of these awards which reflect the innovation and the vision of these outstanding investigators. We are fortunate to have many exceptional young researchers across a wide range of disciplines here in Cambridge and awards such as these highlight some of the amazing research taking place across the university. I wish this year’s recipients all the very best as they begin their new programmes and can’t wait to see the outcomes of their work.”

Iliana Ivanova, European Commissioner for Innovation, Research, Culture, Education and Youth, said:

“ ̽��ֱ��European Commission is proud to support the curiosity and passion of our early-career talent under our Horizon Europe programme. ̽��ֱ��new ERC Starting Grants winners aim to deepen our understanding of the world. Their creativity is vital to finding solutions to some of the most pressing societal challenges. In this call, I am happy to see one of the highest shares of female grantees to date, a trend that I hope will continue. Congratulations to all!”

President of the European Research Council, Prof. Maria Leptin, said:

“Empowering researchers early on in their careers is at the heart of the mission of the ERC. I am particularly pleased to welcome UK researchers back to the ERC. They have been sorely missed over the past years. With fifty grants awarded to researchers based in the UK, this influx is good for the research community overall.”

Nine Cambridge researchers are among the latest recipients of highly competitive and prestigious European Research Council (ERC) Starting Grants.

Luginbuehl lab

Plant roots interacting with arbuscular mycorrhizal fungi. Image: Luginbuehl lab

̽��ֱ��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 – 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.

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Exceptional scientists elected as Fellows of the Royal Society 2023

lw355 — Wed, 10 May 2023 10:52:57 +0000

̽��ֱ��Royal Society is a self-governing Fellowship of many of the world’s most distinguished scientists drawn from all areas of science, engineering and medicine.

̽��ֱ��Society’s fundamental purpose, as it has been since its foundation in 1660, is to recognise, promote and support excellence in science and to encourage the development and use of science for the benefit of humanity.

This year, a total of 80 researchers, innovators and communicators from around the world have been elected as Fellows of the Royal Society for their substantial contribution to the advancement of science. These include 59 Fellows, 19 Foreign Members and two Honorary Fellows.

Sir Adrian Smith, President of the Royal Society said: “I am delighted to welcome our newest cohort of Fellows. These individuals have pushed forward the boundaries of their respective fields and had a beneficial influence on the world beyond. This year’s intake have already achieved incredible things, and I have no doubt that they will continue to do so. I look forward to meeting them and following their contributions in future.”

̽��ֱ��Fellows and Foreign Members join the ranks of Stephen Hawking, Isaac Newton, Charles Darwin, Albert Einstein, Lise Meitner, Subrahmanyan Chandrasekhar and Dorothy Hodgkin.

̽��ֱ��Cambridge Fellows are:

Professor Cathie Clarke FRS

Professor of Theoretical Astrophysics, Institute of Astronomy, and Fellow of Clare College

Clarke studies astrophysical fluid dynamics, including accretion and protoplanetary discs and stellar winds. She was the first to demonstrate how protoplanetary disc formation around low-mass young stars is determined by their radiation field. In 2017 she became the first woman to be awarded the Eddington Medal by the Royal Astronomical Society and in 2022 she became director of the Institute of Astronomy.

She said: “It's a great honour to join the many Cambridge astrophysicists who have held this title. I would like to particularly pay tribute to the many junior colleagues, PhD students and postdocs who have contributed to my research.”

Professor Christopher Jiggins FRS

Professor of Evolutionary Biology (2014), Department of Zoology, and Fellow of St John's College

Jiggins studies adaption and speciation in the Lepidoptera (butterflies and moths). In particular he is interested in studying how species converge due to mimicry as a model for understanding the predictability of evolution and the genetic and ecological causes of speciation. He demonstrated the importance of hybridisation and movement of genes between species in generating novel adaptations. He also works on the agricultural pest cotton bollworm and carries out genomic studies of the insect bioconversion species, black soldier fly.

He said: “I am amazed and delighted to receive this honour, and would thank all the amazing students, and postdocs that I have been lucky enough to work with over the years.”

Dr Philip Jones FRS

Senior Group Leader, Wellcome Sanger Institute and Professor of Cancer Development, ̽��ֱ�� of Cambridge, and Fellow of Clare College

Jones studies how normal cell behaviour is altered by mutation in aging and the earliest stages of cancer development. He focuses on normal skin and oesophagus, which become a patchwork of mutant cells by middle age. He has found that different mutations can either promote or inhibit cancer development giving hope of new ways to prevent cancer in the future. He is also a Consultant in Medical Oncology at Addenbrooke’s Hospital in Cambridge.

He said: “I am delighted to be elected to the Fellowship of the Royal Society. This honour is a tribute to the dedication of my research team and collaborators and support of my mentors and scientific colleagues over many years.”

Dr Lori Passmore FRS

Group Leader, Structural Studies Division, MRC Laboratory of Molecular Biology, and Fellow of Clare Hall

Passmore a cryo-electron microscopist and structural biologist who works at the Medical Research Council (MRC) Laboratory of Molecular Biology and at the ̽��ֱ�� of Cambridge. She is known for her work on multiprotein complexes involved in gene expression and the development of new supports for cryo-EM studies. She also studies the molecular mechanisms underlying Fanconi anemia, a rare genetic disease resulting in an impaired response to DNA damage.

She said: “I am so honoured to be recognised alongside such an exceptional group of scientists. I am grateful to all the trainees, collaborators and colleagues whom I have worked with over the past years - science is truly collaborative and this is a recognition of all the courageous work of many people.”

Professor Peter Sewell FRS

Professor of Computer Science, Department of Computer Science and Technology, and Fellow of Wolfson College

Sewell’s research aims to put the engineering of the real-world computer systems that we all depend on onto better foundations, developing techniques to make systems that are better-understood, more robust and more secure. He and his group are best known for their work on the subtle relaxed-memory concurrency behaviour and detailed sequential semantics of processors and programming languages. He co-leads the CHERI cybersecurity project, for which his team have established mathematically-proven security properties of Arm's Morello industrial prototype architecture.

He said: “This honour is a testament to the work of many excellent colleagues over the years, without whom none of this would have been possible.”

Professor Ivan Smith FRS

Professor of Geometry, Centre for Mathematical Sciences, and Fellow of Caius College

Smith is a mathematician who deals with symplectic manifolds and their interaction with algebraic geometry, low-dimensional topology and dynamics. In 2007, he received the Whitehead Prize for his work in symplectic topology, highlighting the breadth of applied techniques from algebraic geometry and topology, and in 2013 the Adams Prize.

He said: “I am surprised, delighted and hugely honoured to be elected a Fellow of the Royal Society. I’ve been very fortunate to work in a rapidly advancing field, learning it alongside many inspirational and generous collaborators, who should definitely share this recognition.”

Professor William Sutherland CBE FRS

Miriam Rothschild Chair of Conservation Biology, Department of Zoology and Professorial Fellow of St Catharine’s College

Sutherland is a conservation scientist who is interested in improving the processes by which decisions are made. This has involved horizon scanning to identify future issues to reduce the surprises of future developments. His main work has been the industrial-scale collation of evidence to determine which interventions are effective and which are not and then establishing processes for embedding evidence in decision making. He has developed a free, online resource, Conservation Evidence, summarising evidence for the effectiveness of conservation actions to support anyone making decisions about how to maintain and restore biodiversity and an open access book Transforming Conservation: a practical guide to evidence and decision making.

He said: “I am delighted that our work on the means of improving decision making in conservation and elsewhere has been recognised in this way and thank my numerous collaborators.”

Seven outstanding Cambridge researchers have been elected as Fellows of the Royal Society, the UK’s national academy of sciences and the oldest science academy in continuous existence.

These individuals have pushed forward the boundaries of their respective fields and had a beneficial influence on the world beyond

Sir Adrian Smith, President of the Royal Society

Courtesy of ̽��ֱ��Royal Society

̽��ֱ��Royal Society, London

̽��ֱ��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.

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Meet the robot avatars helping Cambridge students combine education and motherhood

sjr81 — Thu, 26 Apr 2018 08:55:23 +0000

Neeta Lakhani and another fellow student are NHS professionals, full-time mothers and part-time students who fell pregnant and gave birth to their children while studying for the Genomic Medicine Masters Programme. Cambridge is believed to be the first university to have used the avatars for classroom teaching.

Using the avatars, which were originally designed to help schoolchildren with long-term illnesses continue their studies, both Neeta and her classmate were able to carry on (virtually) attending their classes in a more profound and engaging way than simply viewing a livestream of the lectures they were missing, or using platforms such as Skype.

̽��ֱ��avatars have microphones, speakers and can move their heads to view both teachers, classmates and presentations – enabling the students to listen, ask questions, talk and interact with classmates and supervisors both during lectures and at breaks.

If the babies are crying, then both mothers can mute the microphones at home so as not to disturb the classroom environment. If they wish to ask a question in class, they can activate a flashing light on the avatar to signal their wish to speak.

Neeta, who alongside her daughter Aniya was filmed for Channel Four News, said: “ ̽��ֱ��way we do it is that that we all get up as we normally do and I get Aniya set up and I get the avatar set up on this end and she just goes through the module with me every day. Whenever she needs attention, I’m able to give it to her without disrupting the class by putting the avatar on silent from my end, but still being able to hear. As soon as she’s settled, I’m able to go back to the avatar.

“I’ve actually found that I’ve concentrated more being at home because it gives me the opportunity to be able to do the two things that I needed to do in the environment that I can most easily do it in. Obviously, the alternative would have been to be in Cambridge and her not be there and I think that would have been very distracting.”

Sarah Morgan, Scientific Training Coordinator at the European Bioinformatics Institute (EMBL-EBI), said: “This was a bit of an experiment for us, but I would say it’s a successful one. ̽��ֱ��robot avatars allowed the two students to participate without physically being in the room. Using the avatars allowed the students to continue their training while caring for their new-borns. It’s certainly inspired us to think outside the box in terms of the needs of our students.”

̽��ֱ��Genomics Medicine Masters Programme is a joint Institute of Continuing Education (ICE) and School of Clinical Medicine course for the ̽��ֱ�� of Cambridge, delivered in collaboration with EMBL-EBI, the Wellcome Sanger Institute, and the Wellcome Genome Campus Advanced Courses and Scientific Conferences.

They are 40cm tall, made of white plastic, and don’t look like your average students, but robot avatars have taken their place in the classroom at Cambridge ̽��ֱ�� – to help two mothers with new-born babies continue their Masters degrees in Genomic Medicine.

I get the avatar set up and my daughter goes through the module with me every day.

Neeta Lakhani

Meet the robot avatars helping Cambridge students combine education and motherhood

European Bioinformatics Institute

̽��ֱ��two student avatars pictured outside the Wellcome Genome Campus

̽��ֱ��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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Unprecedented study of Aboriginal Australians points to one shared Out of Africa migration for modern humans

tdk25 — Wed, 21 Sep 2016 18:00:19 +0000

̽��ֱ��first major genomic study of Aboriginal Australians ever undertaken has confirmed that all present-day non-African populations are descended from the same single wave of migrants, who left Africa around 72,000 years ago.

Researchers sequenced the complete genetic information of 83 Aboriginal Australians, as well as 25 Papuans from New Guinea, to produce a host of significant new findings about the origins of modern human populations. Their work is published alongside several other related papers in the journal Nature.

̽��ֱ��study, by an international team of academics, was carried out in close collaboration with elders and leaders from various Aboriginal Australian communities – some of whom are co-authors on the paper – as well as with various other organisations representing the participating groups.

Alongside the prevailing conclusion, that the overwhelming majority of the genomes of non-Africans alive today stem from one ancestral group of migrants who left Africa together, there are several other standout findings. These include:

Compelling evidence that Aboriginal Australians are descended directly from the first people to inhabit Australia – which is still the subject of periodic political dispute.
Evidence of an uncharacterised – and perhaps unknown – early human species which interbred with anatomically modern humans as they migrated through Asia.
Evidence that a mysterious dispersal from the northeastern part of Australia roughly 4,000 years ago contributed to the cultural links between Aboriginal groups today. These internal migrants defined the way in which people spoke and thought, but then disappeared from most of the continent, in a manner which the researchers describe as “ghost-like”.

̽��ֱ��study’s senior authors are from the ̽��ֱ�� of Cambridge, the Wellcome Trust Sanger Institute, the Universities of Copenhagen, Bern and Griffith ̽��ֱ�� Australia. Within Cambridge, members of the Leverhulme Centre for Evolutionary Studies also contributed to the research, in particular by helping to place the genetic data which the team gathered in the field within the context of wider evidence about early human population and migration patterns.

Professor Eske Willerslev, who holds posts at St John’s College, ̽��ֱ�� of Cambridge, the Sanger Institute and the ̽��ֱ�� of Copenhagen, initiated and led the research. He said: “ ̽��ֱ��study addresses a number of fundamental questions about human evolution – how many times did we leave Africa, when was Australia populated, and what is the diversity of people in and outside Australia?”

“Technologically and politically, it has not really been possible to answer those questions until now. We found evidence that there was only really one wave of humans who gave rise to all present-day non-Africans, including Australians.”

Anatomically modern humans are known to have left Africa approximately 72,000 years ago, eventually spreading across Asia and Europe. Outside Africa, Australia has one of the longest histories of continuous human occupation, dating back about 50,000 years.

Some researchers believe that this deep history indicates that Papuans and Australians stemmed from an earlier migration than the ancestors of Eurasian peoples; others that they split from Eurasian progenitors within Africa itself, and left the continent in a separate wave.

Until the present study, however, the only genetic evidence for Aboriginal Australians, which is needed to investigate these theories, came from one tuft of hair (taken from a long-since deceased individual), and two unidentified cell lines.

̽��ֱ��new research dramatically improves that picture. Working closely with community elders, representative organisations and the ethical board of Griffith ̽��ֱ��, Willerslev and colleagues obtained permission to sequence dozens of Aboriginal Australian genomes, using DNA extracted from saliva.

This was compared with existing genetic information about other populations. ̽��ֱ��researchers modelled the likely genetic impact of different human dispersals from Africa and towards Australia, looking for patterns that best matched the data they had acquired. Dr Marta Mirazon Lahr and Professor Robert Foley, both from the Leverhulme Centre, assisted in particular by analysing the likely correspondences between this newly-acquired genetic evidence and a wider framework of existing archaeological and anthropological evidence about early human population movements.

Dr Manjinder Sandhu, a senior author from the Sanger Institute and ̽��ֱ�� of Cambridge, said: “Our results suggest that, rather than having left in a separate wave, most of the genomes of Papuans and Aboriginal Australians can be traced back to a single ‘Out of Africa’ event which led to modern worldwide populations. There may have been other migrations, but the evidence so far points to one exit event.”

̽��ֱ��Papuan and Australian ancestors did, however, diverge early from the rest, around 58,000 years ago. By comparison, European and Asian ancestral groups only become distinct in the genetic record around 42,000 years ago.

̽��ֱ��study then traces the Papuan and Australian groups’ progress. Around 50,000 years ago they reached “Sahul” – a prehistoric supercontinent that originally united New Guinea, Australia and Tasmania, until these regions were separated by rising sea levels approximately 10,000 years ago.

̽��ֱ��researchers charted several further “divergences” in which various parts of the population broke off and became genetically isolated from others. Interestingly, Papuans and Aboriginal Australians appear to have diverged about 37,000 years ago – long before they became physically separated by water. ̽��ֱ��cause is unclear, but one reason may be the early flooding of the Carpentaria basin, which left Australia connected to New Guinea by a strip of land that may have been unfavourable for human habitation.

Once in Australia, the ancestors of today’s Aboriginal communities remained almost completely isolated from the rest of the world’s population until just a few thousand years ago, when they came into contact with some Asian populations, followed by European travellers in the 18th Century.

Indeed, by 31,000 years ago, most Aboriginal communities were genetically isolated from each other. This divergence was most likely caused by environmental barriers; in particular the evolution of an almost impassable central desert as the Australian continent dried out.

Assistant Professor Anna-Sapfo Malaspinas, from the Universities of Copenhagen and Bern, and a lead author, said: “ ̽��ֱ��genetic diversity among Aboriginal Australians is amazing. Because the continent has been populated for such a long time, we find that groups from south-western Australia are genetically more different from north-eastern Australia, than, for example, Native Americans are from Siberians.”

Two other major findings also emerged. First, the researchers were able to reappraise traces of DNA which come from an ancient, extinct human species and are found in Aboriginal Australians. These have traditionally been attributed to encounters with Denisovans – a group known from DNA samples found in Siberia.

In fact, the new study suggests that they were from a different, as-yet uncharacterised, species. “We don’t know who these people were, but they were a distant relative of Denisovans, and the Papuan/Australian ancestors probably encountered them close to Sahul,” Willerslev said.

Finally, the research also offers an intriguing new perspective on how Aboriginal culture itself developed, raising the possibility of a mysterious, internal migration 4,000 years ago.

About 90% of Aboriginal communities today speak languages belonging to the “Pama-Nyungan” linguistic family. ̽��ֱ��study finds that all of these people are descendants of the founding population which diverged from the Papuans 37,000 years ago, then diverged further into genetically isolated communities.

This, however, throws up a long-established paradox. Language experts are adamant that Pama-Nyungan languages are much younger, dating back 4,000 years, and coinciding with the appearance of new stone technologies in the archaeological record.

Scientists have long puzzled over how – if these communities were completely isolated from each other and the rest of the world – they ended up sharing a language family that is much younger? ̽��ֱ��traditional answer has been that there was a second migration into Australia 4,000 years ago, by people speaking this language.

But the new research finds no evidence of this. Instead, the team uncovered signs of a tiny gene flow, indicating a small population movement from north-east Australia across the continent, potentially at the time the Pama-Nyungan language and new stone tool technologies appeared.

These intrepid travellers, who must have braved forbidding environmental barriers, were small in number, but had a significant, sweeping impact on the continent’s culture. Mysteriously, however, the genetic evidence for them then disappears. In short, their influential language and culture survived – but they, as a distinctive group, did not.

“It’s a really weird scenario,” Willerslev said. “A few immigrants appear in different villages and communities around Australia. They change the way people speak and think; then they disappear, like ghosts. And people just carry on living in isolation the same way they always have. This may have happened for religious or cultural reasons that we can only speculate about. But in genetic terms, we have never seen anything like it before.”

̽��ֱ��paper, A Genomic History of Aboriginal Australia, is published in Nature. doi:10.1038/nature18299.

Inset images: Professor Eske Willerslev talking to Aboriginal elders in the Kalgoorlie area in southwestern Australia in 2012. (Photo credit: Preben Hjort, Mayday Film). / Map showing main findings from the paper. Credit: St John's College, Cambridge.

̽��ֱ��first significant investigation into the genomics of Aboriginal Australians has uncovered several major findings about early human populations. These include evidence of a single “Out of Africa” migration event, and of a previously unidentified, “ghost-like” population spread which provided a basis for the modern Aboriginal cultural landscape.

We found evidence that there was only really one wave of humans who gave rise to all present-day non-Africans, including Australians

Eske Willerslev

Preben Hjort, Magus Film

Aubrey Lynch, elder from the Wongatha Aboriginal language group, who participated in the study.

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

Yes

Tasmanian Devils and the transmissible cancer that threatens their extinction

amb206 — Wed, 14 Oct 2015 11:05:42 +0000

Scroll to the end of the article to listen to the podcast.

In 1996 a wildlife photographer working in a remote part of Tasmania noticed a ‘Tassie devil’ (the affectionate name for the Tasmanian devil) with a tumour on its face. He assumed that the animal’s facial disfigurement was a one-off – but within a year he spotted another devil with a similar problem. He notified the authorities and, as increasing numbers of affected devils were seen, it was established that the animals were suffering from a wave of devastating facial tumours.

Ten years after the first tumour was spotted, scientists revealed that the lesions weren’t ordinary tumours. They were caused by a transmissible cancer – an extremely rare type of disease, in which living cancer cells are physically transmitted between animals. Only three transmissible cancers are known in nature, and these affect dogs, clams and Tasmanian devils respectively. In the case of devils, the cancer cells are thought to be transmitted by biting.

Once they have acquired the cancer, devils usually live just a matter of months. No treatment exists. As the number of sightings of afflicted animals continued to escalate, with the disease moving across the island from east to west, it became clear that the Tasmanian devil was threatened with extinction.

Dr Elizabeth Murchison, a specialist in comparative oncology and genetics at the ̽��ֱ�� of Cambridge’s Department of Veterinary Medicine, was brought up in Tasmania. ̽��ֱ��presence of Tasmanian devils – which are the emblem of the Tasmanian state – was part of her rural childhood. Devils are scavengers and, by disposing of dead animals, they provide a useful service as the ‘garbage bins of the bush’.

Murchison studied genetics and biochemistry at the ̽��ֱ�� of Melbourne, and then studied for her PhD in molecular biology at Cold Spring Harbor Laboratory, New York. Her interest in solving the puzzle of the tumours began in 2006 when she came across a roadkill devil with a tumour in a wild area of Tasmania. This confronting finding triggered her desire to understand this strange disease.

Her specialism is cancer genetics; her research focuses on developing an understanding of the evolution of the DNA of transmissible cancer by tracing it backwards in time to track the steps by which a normal cell mutates to become a cancerous one.

In 2012, while working at the Sanger Institute, near Cambridge, Murchison led a collaborative group of scientists using new DNA sequencing technologies to unlock the Tasmanian devil genome, as well as the genome of the devils’ transmissible cancer. This research led to the discovery that the Tasmanian devil cancer probably emerged relatively recently in a single female Tasmanian devil. ̽��ֱ��cells derived from this cancer have continued to survive by “metastasising” through the Tasmanian devil population.

More recently, Murchison has concentrated on understanding the genetic differences between tumours occurring in different Tasmanian devils. Although tumours in all Tasmanian devils are a “clone”, derived from the same original animal, the cancer lineage has diverged and acquired new mutations during its spread through the devil population.

This work requires close collaboration with many scientists, especially those back in her native Tasmania. She says: “I wake up to emails from the other side of the world, updating me on the progress of field work back in Tasmania. We skype regularly because working closely together as an interdisciplinary team is the best way to try to understand this disease and help the devils as soon as possible.”

In addition to working on the Tasmanian devil, Murchison’s group studies canine transmissible venereal tumour (CTVT). CTVT is a sexually transmitted genital cancer, spread by the transfer of living cancer cells between dogs. In contrast to the devil cancer, which emerged relatively recently, CTVT probably emerged thousands of years ago. ̽��ֱ��disease has now spread widely and affects dogs around the world. Murchison’s group has recently sequenced the genome of CTVT, and this work has shed light on the evolution of a unique cancer.

One of the most disquieting aspects of transmissible cancers is the fact that they are, effectively, parasites. Once the devil cancer cells are introduced to a new host by means of a bite, they go undetected by the devil’s immune system and thus flourish, eventually killing the animal. By sequencing samples of DNA taken from the devil cancer from 2003 onwards, Murchison is trying to understand how this cancer evolved and changed with time. Her research makes a valuable contribution to the potential development of a vaccine or other therapy to protect devils against the disease.

Over the past decade, the Tasmanian authorities have worked hard to safeguard the future of the Tasmanian devil. An ‘insurance’ population of healthy devils has been spread among Australian parks and zoos. Most recently, a colony of unaffected devils has been established on Maria Island, a national park off the coast of eastern Tasmania.

“Research into this devastating disease in Tasmanian devils is starting to illuminate the underlying processes that caused this unusual disease and promoted its transmission. We hope that our research may also help us to understand basic processes that underlie cancer evolution more generally, including in humans. But, of course, we are motivated by the goal that our research will help to protect this unique and iconic marsupial from extinction,” said Murchison.

Next in the Cambridge Animal Alphabet: U is for an animal used in heraldry since the 15th century and in recipes for anti-poison since the 1700s.

Have you missed the series so far? Catch up on Medium here.

Inset images: Tasmanian devil with facial tumours (Elizabeth Murchison); Video clips courtesy of the Save the Tasmanian Devil Program , DPIPWE; Tasmanian devil (Joe Le Nevez).

The Cambridge Animal Alphabet series celebrates Cambridge's connections with animals through literature, art, science and society. Here, T is for Tasmanian Devil and the researchers studying the transmissable cancer that threatens these marsupials with extinction.

We are motivated by the goal that our research will help to protect this unique and iconic marsupial from extinction

Elizabeth Murchison

Tasmanian Devil

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

Yes

11,000-year-old living dog cancer reveals its secrets

fpjl2 — Thu, 23 Jan 2014 19:05:00 +0000

This cancer, which causes grotesque genital tumours in dogs around the world, first arose in a single dog that lived about 11,000 years ago. ̽��ֱ��cancer survived after the death of this dog by the transfer of its cancer cells to other dogs during mating.

̽��ֱ��genome of this 11,000-year-old cancer carries about two million mutations – many more mutations than are found in most human cancers, the majority of which have between 1,000 and 5,000 mutations. ̽��ֱ��team used one type of mutation, known to accumulate steadily over time as a “molecular clock”, to estimate that the cancer first arose 11,000 years ago.

“ ̽��ֱ��genome of this remarkable long-lived cancer has demonstrated that, given the right conditions, cancers can continue to survive for more than 10,000 years despite the accumulation of millions of mutations,” said Dr Elizabeth Murchison from Cambridge’s Department of Veterinary Medicine and the Wellcome Trust Sanger Institute, who is lead author on the study, published today in the journal Science.

̽��ֱ��genome of the transmissible dog cancer still harbours the genetic variants of the individual dog that first gave rise to the cancer 11,000 years ago. Analysis of these genetic variants revealed that this dog may have resembled an Alaskan Malamute or Husky. It probably had a short, straight coat that was coloured either grey/brown or black. Its genetic sequence could not determine if this dog was a male or a female, but did indicate that it was a relatively inbred individual.

“We do not know why this particular individual gave rise to a transmissible cancer,” said Murchison, “But it is fascinating to look back in time and reconstruct the identity of this ancient dog whose genome is still alive today in the cells of the cancer that it spawned.”

Transmissible dog cancer is a common disease found in dogs around the world today. ̽��ֱ��genome sequence has helped scientists to further understand how this disease has spread.

“ ̽��ֱ��patterns of genetic variants in tumours from different continents suggested that the cancer existed in one isolated population of dogs for most of its history,” says Dr Murchison. “It spread around the world within the last 500 years, possibly carried by dogs accompanying seafarers on their global explorations during the dawn of the age of exploration.”

Transmissible cancers are extremely rare in nature. Cancers, in humans and animals, arise when a single cell in the body acquires mutations that cause it to produce more copies of itself. Cancer cells often spread to different parts of the body in a process known as metastasis.

However, it is very rare for cancer cells to leave the bodies of their original hosts and to spread to other individuals. Apart from the dog transmissible cancer, the only other known naturally occurring transmissible cancer is an aggressive transmissible facial cancer in Tasmanian devils that is spread by biting.

“ ̽��ֱ��genome of the transmissible dog cancer will help us to understand the processes that allow cancers to become transmissible,” said Professor Sir Mike Stratton, senior author and Director of the Sanger Institute.

“Although transmissible cancers are very rare, we should be prepared in case such a disease emerged in humans or other animals. Furthermore, studying the evolution of this ancient cancer can help us to understand factors driving cancer evolution more generally.”

Inset image: Elizabeth Murchison and Andrea Strakova, ̽��ֱ�� of Cambridge and Genome Research Limited

Scientists have sequenced the genome of the world’s oldest continuously surviving cancer, a transmissible genital cancer that affects dogs.

It is fascinating to look back in time and reconstruct the identity of this ancient dog whose genome is still alive today in the cells of the cancer that it spawned

Elizabeth Murchison

Paolo Lottini via Flickr

Non svegliare il can che dorme

Cambridge Science Festival event - 8pm, Tuesday 18 March

Transmissible cancers in dogs and Tasmanian devils
Join Andrea Strakova for a talk which will reveal unexpected findings about two unique cancers which have adapted to transfer by the means of living cancer cells between their hosts – Tasmanian devils and domestic dogs. We will explore how a cancer can become transmissible, despite the fact that it is usually considered to be a malignant transformation of cells of your own body.

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Novel genetic mutations cause low metabolic rate and obesity

sj387 — Fri, 25 Oct 2013 07:43:45 +0000

Researchers from the ̽��ֱ�� of Cambridge have discovered a novel genetic cause of severe obesity which, although relatively rare, demonstrates for the first time that genes can reduce basal metabolic rate – how the body burns calories.

Previous studies (performed by David Powell and colleagues at Lexicon Pharmaceuticals in Texas) demonstrated that when the gene KSR2 (Kinase Suppressor of Ras 2) was deleted in mice, the animals became severely obese. As a result of this research, Professor Sadaf Farooqi from the ̽��ֱ�� of Cambridge’s Wellcome Trust-MRC Institute of Metabolic Science decided to explore whether KSR2 mutations might also lead to obesity in humans.

In collaboration with Dr Ines Barroso’s team at the Wellcome Trust Sanger Institute, the researchers sequenced the DNA from over 2,000 severely obese patients and identified multiple mutations in the KSR2 gene. ̽��ֱ��research was published online today, 24 October, in the journal Cell.

KSR2 belongs to a group of proteins called scaffolding proteins which play a critical role in ensuring that signals from hormones such as insulin are correctly processed by cells in the body to regulate how cells grow, divide and use energy. To investigate how KSR2 mutations might lead to obesity, Professor Farooqi’s team performed a series of experiments which showed that many of the mutations disrupt these cellular signals and, importantly, reduce the ability of cells to use glucose and fatty acids.

Patients who had the mutations in KSR2 had an increased drive to eat in childhood, but also a reduced metabolic rate, indicating that they have a reduced ability to use up all the energy that they consume. A slow metabolic rate can be found in people with an underactive thyroid gland, but in these patients thyroid blood tests were in the normal range - eliminating this as a possible explanation for their low metabolic rate. People have speculated for a long time that some individuals may burn calories more slowly than others. ̽��ֱ��findings in this study provide the first evidence that defects in a particular gene, KSR2, can affect a person’s metabolic rate and how their bodies processed calories.

Professor Farooqi said: “Up until now, the genes we have identified that control body weight have largely affected appetite. However, KSR2 is different in that it also plays a role in regulating how energy is used in the body. In the future, modulation of KSR2 may represent a useful therapeutic strategy for obesity and type 2 diabetes.”

Changes in diet and levels of physical activity underlie the recent increase in obesity in the UK and worldwide. However, there is a lot of variation in how much weight people gain. This variation between people is largely influenced by genetic factors, and many of the genes involved act in the brain. ̽��ֱ��discovery of a new obesity gene, KSR2, adds another level of complexity to the body’s mechanisms for regulating weight. ̽��ֱ��Cambridge team is continuing to study the genetic factors influencing obesity, findings which they hope to translate into beneficial therapies in the future.

Professor Farooqi’s research was funded by the Wellcome Trust.

Researchers believe the gene could be a useful therapeutic target for treating obesity and type 2 diabetes

In the future, modulation of KSR2 may represent a useful therapeutic strategy for obesity and type 2 diabetes

Sadaf Farooqi

Shaury Nash

DNA code

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Cause of rare growth disease discovered

bjb42 — Sun, 24 Jun 2012 18:00:54 +0000

A rare genetic disease which causes some parts of the body to grow excessively has been linked to a cancer-associated mutation that drives cell growth, potentially paving the way for new treatments. ̽��ֱ��research findings were published today, 24 June, in Nature Genetics.

An international collaboration among the ̽��ֱ�� of Cambridge, the Sanger Institute, and the Babraham Institute in the UK and the National Institute for Health in the US has discovered that unrestrained and sometimes massive fatty ‘overgrowth’ affecting only some body regions is caused by mutations in the phosphatidylinositol-3-kinase (PI3K)/AKT signalling pathway (which is critical for cellular growth and metabolism).

̽��ֱ��types of mutations which cause these overgrowths typically arise during embryonic development. Unlike conditions caused by genetic mutations which are transmitted from parents (in which every cell in the body is affected), in this condition only the ‘offspring’ of the cell where the mutation occurs carry the change. This accounts for why only some parts of the body are affected.

̽��ֱ��scientists from the ̽��ֱ�� of Cambridge and the Sanger Institute, who were funded mainly by the Wellcome Trust, first studied a patient who had severe overgrowth of her legs but a normal upper body. By conducting a genetic analysis of cells sampled from the affected and unaffected areas, they were able to identify a critical mutation which caused the overgrowth in her legs. Scientists at the Babraham Institute then made use of their unique lipidomics mass spectrometry capability to demonstrate abnormal activation of the signalling pathway in cells from the leg but not the arm. These studies were extended in collaboration with scientists at the US National Institute for Health in Maryland, leading to discovery of nine other patients with similar mutations, confirming the results and suggesting that activation of the PI3K pathway may be a common cause of this form of fatty overgrowth.

Dr Robert Semple, from the ̽��ֱ�� of Cambridge Metabolic Research Laboratories at the Institute of Metabolic Science, said: “ ̽��ֱ��mutations we have found are well known as ‘cancer mutations’. However, in cancers they are found with numerous other genetic changes, while here they are apparently in isolation.”

“Studying our patients will thus give new information about the specific role played by these mutations in cancer. Moreover, the major effort to make drugs targeting these mutations for cancer therapy should benefit people with this rare problem, and when drugs safe enough for long-term use are developed they may offer for the first time a targeted, and effective, non-surgical treatment for the excessive growth. We are testing currently available drugs in cells at present.”

Dr Inȇs Barroso, from the Wellcome Trust Sanger Institute, said “We wanted to understand the biology behind this rare and debilitating disorder and thought exome sequencing - sequencing the region of the genome where genetic material is translated into proteins - would be a powerful approach to facilitate the discovery of the underlying mutation. Using DNA sequencing we found that a mutation associated with cancer in the gene PIK3CA was found only in the affected cells of patients”.

Professor Michael Wakelam from the Babraham Institute said “This study exemplifies the importance of collaboration between basic and clinical scientists in translating methodologies and concepts from the research lab to bring about greater understanding and potentially treatment of human disease.”

Scientists hopeful discovery will provide a biological target for drug therapy.

̽��ֱ��mutations we have found are well known as ‘cancer mutations’. However, in cancers they are found with numerous other genetic changes, while here they are apparently in isolation.

Robert Semple

Nature Genetics.

Example of fatty overgrowth, affecting specific body regions, caused by mutations in the phosphatidylinositol 3 kinase PI3K (AKT) signalling pahtway.

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