̽��ֱ�� of Cambridge - Austin Smith

Cambridge researchers win European Research Council funding

sc604 — Thu, 28 Mar 2019 11:00:00 +0000

Two hundred and twenty-two senior scientists from across Europe were awarded grants in today’s announcement, representing a total of €540 million in research funding. ̽��ֱ��UK has 47 grantees in this year’s funding round, the most of any ERC participating country.

ERC grants are awarded through open competition to projects headed by starting and established researchers, irrespective of their origins, who are working or moving to work in Europe. ̽��ֱ��sole criterion for selection is scientific excellence.

ERC Advanced Grants are designed to support excellent scientists in any field with a recognised track record of research achievements in the last ten years.

Professor Clare Grey from the Department of Chemistry, and a Fellow of Pembroke College, leads a project focused on the development of longer lasting, higher energy density and cheaper rechargeable batteries, one of society’s major technological challenges. Batteries are currently the limiting components in the shift from gasoline-powered to electric vehicles.

Using a variety of experimental techniques, including dynamic nuclear polarisation NMR spectroscopy, Grey and her team will explore a variety of different battery chemistries, including more traditional lithium-ion and newer solid state and redox-flow batteries, with a particular focus on understanding the interfaces and interphases that form in these systems. ̽��ֱ��interdisciplinary project combines analytical and physical chemistry, materials characterisation, electrochemistry and electronic structures of materials, interfaces and nanoparticles. ̽��ֱ��final result will be a significantly improved understanding of the structures of new types of batteries and how they evolve during the charge-discharge cycle, coupled with strategies for designing improved battery structures.

Professor Cecilia Mascolo from the Department of Computer Science and Technology, and a Fellow of Jesus College, will lead a project focused on the use of mobile devices for medical diagnostics. Mascolo and her team will study how the microphone in mobile and wearable devices may be used to diagnose and monitor various health conditions since sounds from the human body can be indicators of disease or the onsets of disease.

While audio sensing in a mobile context is inexpensive to deploy and can reach people who may not have access to or be able to afford other diagnostic tests, it does come with challenges which threaten its use in clinical context: namely its power-hungry nature and the sensitivity of the data it collects. Mascolo’s ERC funding will support the development of a systematic framework to link sounds to disease diagnosis while addressing power consumption and privacy concerns by maximising the use of local hardware resources with power optimisation and accuracy.

Professor Christopher Reynolds from the Institute of Astronomy, and a Fellow of Sidney Sussex College, leads a project focused on the feedback from supermassive black holes at the centre of galaxies. These supermassive black holes have a profound influence on the evolution of galaxies and galaxy groups/clusters, but fundamental questions remain.

To help address these questions, Reynolds and his team are studying the highly luminous central regions of galaxies around the black hole, known as active galactic nuclei (AGN). Reynolds’ ERC funding will support a set of projects to explore the multi-scale physics of AGN feedback. A new theoretical understanding of AGN feedback as a function of mass, environment, and cosmic time will be essential for interpreting the torrent of data from current and future observatories, and understanding some of the most powerful phenomena in the universe.

Professor Alfonso Martinez Arias from the Department of Genetics will lead a project focused on understanding the early stages of mammalian embryogenesis. ̽��ֱ��development of an embryo requires the spatially structured emergence of tissues and organs, a process which relies on the early establishment of a coordinate system that acts as a template for the organism. Exactly how this process occurs is an open question and one which is difficult to investigate experimentally, particularly in mammals.

Using gastruloids, a stem cell-based experimental system they have developed, Martinez Arias and his team will probe into the functional relationships between the mechanical activities of multicellular ensembles and the dynamics that control the organisation and shape of the mammalian body plan: the arrangement of tissue and organs with reference to a global coordinate system.

Finally, Professor Austin Smith from the Wellcome - MRC Cambridge Stem Cell Institute and the Department of Biochemistry will lead a project on the plasticity of the pluripotent stem cell network. Pluripotent stem cells have the potential to become any of the cells and tissues in the body, but the evolutionary origins of this phenomenon are unclear.

Using a cross-disciplinary approach, Smith and his team hope to uncover the core biological programme moulded by evolution into different forms. ̽��ֱ��team are investigating the molecular logic governing early development, lineage plasticity, pluripotent identity and stem cell self-renewal.

̽��ֱ��President of the European Research Council (ERC), Professor Jean-Pierre Bourguignon, said: “Since 2007, the European Research Council has attracted and financed some of the most audacious research proposals, and independent evaluations show that this approach has paid off. With this call, another 222 researchers from all over Europe and beyond will pursue their best ideas and are in an excellent position to trigger breakthroughs and major scientific advances.”

Carlos Moedas, European Commissioner for Research, Science and Innovation, said: “ ̽��ֱ��ERC Advanced Grants back outstanding researchers throughout Europe. Their pioneering work has the potential to make a difference in people’s everyday life and deliver solutions to some of our most urgent challenges. ̽��ֱ��ERC gives these bright minds the possibility to follow their most creative ideas and to play a decisive role in the advancement of all domains of knowledge.”

Five researchers at the ̽��ֱ�� of Cambridge have won advanced grants from the European Research Council (ERC), Europe’s premier research funding body.

̽��ֱ��ERC gives these bright minds the possibility to follow their most creative ideas and to play a decisive role in the advancement of all domains of knowledge

Carlos Moedas

̽��ֱ�� of Cambridge

Left to right: Christopher Reynolds, Cecilia Mascolo, Alfonso Martinez Arias

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Scientists develop very early stage human stem cell lines for first time

cjb250 — Fri, 04 Mar 2016 08:41:37 +0000

As well as a potential source of stem cells for use in regenerative medicine, the technique could open up new avenues of research into disorders such as Down’s syndrome.

̽��ֱ��ability to derive naïve stem cells has been possible for over thirty years from mouse embryos, using a technique developed by Sir Martin Evans and Professor Matthew Kaufman during their time at Cambridge, but this is the first time this has been possible from human embryos.

Human pluripotent stem cells for use in regenerative medicine or biomedical research come from two sources: embryonic stem cells, derived from fertilised egg cells discarded from IVF procedures; and induced pluripotent stem cells, where skin cells are reprogrammed to a pluripotent form. However, these cells are already “primed” for differentiation into specific cell types. In contrast, all instructions have been erased in naïve cells, which may make it easier to direct them into any cell type of interest.

Recently naïve-like human induced pluripotent stem cells have been created by reprogramming but it has been unknown whether they can also be obtained directly from the human embryo.

When an egg cell is fertilised by a sperm, it begins to divide and replicate before the embryo takes shape. Around day five, the embryonic cells cluster together and form a structure called the ‘blastocyst’. This occurs before implantation into the uterus. ̽��ֱ��blastocyst comprises three cell types: cells that will develop into the placenta and allow the embryo to attach to the womb; and cells that form the ‘yolk sac’, which provides nutrients to the developing foetus; and the ‘epiblast’ comprising the naïve cells that will develop into the future body.

In research published today in the journal Stem Cell Reports, scientists from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute managed to remove cells from the blastocyst at around day six and grow them individually in culture. By separating the cells, the researchers in effect stopped them ‘talking’ to each other, preventing them from being steered down a particular path of development.

“Until now it hasn’t been possible to isolate these naïve stem cells, even though we’ve had the technology to do it in mice for thirty years – leading some people to doubt it would be possible,” explains Ge Guo, the study’s first author, “but we’ve managed to extract the cells and grow them individually in culture. Naïve stem cells have many potential applications, from regenerative medicine to modelling human disorders.”

Naïve pluripotent stem cells in principle have no restrictions on the types of adult tissue into which they can develop, which means they may have promising therapeutic uses in regenerative medicine to treat devastating conditions that affect various organs and tissues, particularly those that have poor regenerative capacity, such as the heart, brain and pancreas.

Dr Jenny Nichols, joint senior author of the study, says that one of the most exciting applications of their new technique would be to study disorders that arise from cells that contain an abnormal number of chromosomes. Ordinarily, the body contains 23 pairs of identical chromosomes (22 pairs and one pair of sex chromosomes), but some children are born with additional copies, which can cause problems – for example, children with Down’s syndrome are born with three copies of chromosome 21.

“Even in many ‘normal’ early-stage embryos, we find several cells with an abnormal number of chromosomes,” explains Dr Nichols. “Because we can separate the cells and culture them individually, we could potentially generate ‘healthy’ and ‘affected’ cell lines. This would allow us to generate and compare tissues of two models, one ‘healthy’ and one that is genetically-identical other than the surplus chromosome. This could provide new insights into conditions such as Down’s syndrome.”

̽��ֱ��research was supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Swiss National Science Foundation and the Wellcome Trust.

Reference
Guo, G et al. Naïve pluripotent stem cells derived directly from isolated cells of the human inner cell mass; Stem Cell Reports; e-pub 3 March 2015. DOI: 10.1016/j.stemcr.2016.02.005

Scientists at the ̽��ֱ�� of Cambridge have for the first time shown that it is possible to derive from a human embryo so-called ‘naïve’ pluripotent stem cells – one of the most flexible types of stem cell, which can develop into all human tissue other than the placenta.

Until now it hasn’t been possible to isolate human naïve stem cells, even though we’ve had the technology to do it in mice for thirty years – leading some people to doubt it would be possible

Ge Guo

Colonies of human naïve embryonic stem cells grown on mouse feeder cells

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Rewiring stem cells

sc604 — Thu, 09 Jan 2014 17:00:00 +0000

A fast and comprehensive method for determining the function of genes could greatly improve our understanding of a wide range of diseases and conditions, such as heart disease, liver disease and cancer.

̽��ֱ��method uses stem cells with a single set of chromosomes, instead of the two sets found in most cells, to reveal what causes the “circuitry” of stem cells to be rewired as they begin the process of conversion into other cell types. ̽��ֱ��same method could also be used to understand a range of biological processes.

Embryonic stem cells rely on a particular gene circuitry to retain their original, undifferentiated state, making them self-renewing. ̽��ֱ��dismantling of this circuitry is what allows stem cells to start converting into other types of cells - a process known as cell differentiation - but how this happens is poorly understood.

Researchers from the ̽��ֱ�� of Cambridge Wellcome Trust-Medical Research Council Stem Cell Institute have developed a technique which can pinpoint the factors which drive cell differentiation, including many that were previously unidentified. ̽��ֱ��method, outlined in the Thursday (9 January) edition of the journal Cell Stem Cell, uses stem cells with a single set of chromosomes to uncover how cell differentiation works.

Cells in mammals contain two sets of chromosomes – one set inherited from the mother and one from the father. This can present a challenge when studying the function of genes, however: as each cell contains two copies of each gene, determining the link between a genetic change and its physical effect, or phenotype, is immensely complex.

“ ̽��ֱ��conventional approach is to work gene by gene, and in the past people would have spent most of their careers looking at one mutation or one gene,” said Dr Martin Leeb, who led the research, in collaboration with Professor Austin Smith. “Today, the process is a bit faster, but it’s still a methodical gene by gene approach because when you have an organism with two sets of chromosomes that’s really the only way you can go.”

Dr Leeb used unfertilised mouse eggs to generate embryonic stem cells with a single set of chromosomes, known as haploid stem cells. These haploid cells show all of the same characteristics as stem cells with two sets of chromosomes, and retain the same full developmental potential, making them a powerful tool for determining how the genetic circuitry of mammalian development functions.

̽��ֱ��researchers used transposons – “jumping genes”– to make mutations in nearly all genes. ̽��ֱ��effect of a mutation can be seen immediately in haploid cells because there is no second gene copy. Additionally, since embryonic stem cells can convert into almost any cell type, the haploid stem cells can be used to investigate any number of conditions in any number of cell types. Mutations with important biological effects can then rapidly be traced to individual genes by next generation DNA sequencing.

“This is a powerful and revolutionary new tool for discovering how gene circuits operate,” said Dr Leeb. “ ̽��ֱ��cells and the methodology we’ve developed could be applied to a huge range of biological questions.”

For more information on this story, contact Sarah Collins on sarah.collins@admin.cam.ac.uk.

A new technique for determining what causes stem cells to convert into other cell types could revolutionise our understanding of how genes function.

̽��ֱ��cells and the methodology we’ve developed could be applied to a huge range of biological questions.

Martin Leeb

Chromosomes in haploid mouse embryonic stem cells

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Patenting ethics in stem cell research

lw355 — Thu, 28 Apr 2011 07:53:03 +0000

A storm could soon hit European courts over whether it is ethical to patent work involving human embryonic stem cell lines. Scientists fear that the lengthy legal debate could spark more restrictive legislation, or even a ban on such work in Europe.

Professor Austin Smith, Director of the Wellcome Trust Centre for Stem Cell Research at the ̽��ֱ�� of Cambridge and scientific co-ordinator of the EuroSyStem Project, and other prominent coordinators of European stem cell research bodies, weigh in with an open letter in this week’s Nature supporting the right to patent in this field, now under review by the European Court of Justice.

Arguing that these established cell lines do not involve commercialisation of the human embryo and are superior to other available technologies for developing therapies, they say that European bioindustry must have patent protection in order to realise the clinical benefits of stem cell lines.

“We trust that [the court] will deliberate on the full implications before making a legally binding ruling,” say the signatories.

̽��ֱ��letter plus comments from ethicists and scientists is available on eurostemcell.org, along with the opportunity to comment or add a signature at www.eurostemcell.org/stem-cell-patents

̽��ֱ��EuroSyStem Project is a member of EuroStemCell and is an EC-funded partnership between Europe's top stem cell research groups. ̽��ֱ��Project aims to interlink complementary biological and computational expertise to drive the generation of new knowledge on the characteristics of normal and abnormal stem cells.

Scientists say ‘No’ to a ban on stem cell patents recommended by the European Court of Justice.

European bioindustry must have patent protection in order to realise the clinical benefits of stem cell lines.

Dr Thomas Moreau

Human embryonic stem cell colonies

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Funding to boost scientific links with Japan

bjb42 — Thu, 01 Apr 2010 09:37:07 +0000

Professor Austin Smith, Director of the Wellcome Trust Centre for Stem Cell Research, has received a Japan Partnering Award from the Biotechnology and Biological Sciences Research Council (BBSRC). This scheme provides funding for BBSRC-supported researchers to build and foster long-term collaborations with Japanese partners.

̽��ֱ��award will enable Professor Smith and colleagues in Cambridge to collaborate closely with Dr Hitoshi Niwa and other researchers at the RIKEN Center for Developmental Biology in Kobe, Japan. ̽��ֱ��project also involves Dr Paul Bertone, a biocomputational expert at the European Bioinformatics Institute near Cambridge, and Dr Kathryn Lilley, Director of the Cambridge Centre for Proteomics.

̽��ֱ��collaborative effort is tackling an emerging area of research: the systems biology of stem cells. Systems biology integrates complex information about whole biological systems to understand how they function. Like stem cell biology, it has been a fast-growing research field over the past decade.

‘Only recently has it been realistic to start bridging the two approaches in order to answer questions about the behaviour and decision-making pathways of stem cells,’ explained Professor Smith. ‘It’s an exciting but challenging area, and it makes very good sense for researchers in Cambridge and Japan to share complementary experience, tools and resources.’

Commenting on the awards, which have been made to four research groups in the UK, Professor Douglas Kell, BBSRC Chief Executive, said: ‘Modern bioscience demands international collaboration. By working together across international borders we can generate faster progress and higher quality science than we can alone.’

For more information, please contact Professor Austin Smith (austin.smith@cscr.cam.ac.uk). Professor Smith was recently awarded the prestigious 2010 Louis-Jeantet Prize for Medicine for his contributions to stem cell research.

Researchers in Cambridge and Japan will be working together towards a more integrated understanding of how stem cells make decisions.

Modern bioscience demands international collaboration. By working together across international borders we can generate faster progress and higher quality science than we can alone.

Professor Douglas Kell

Dr Jason Wray

Embryonic stem cells

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