̽��ֱ�� of Cambridge - development

Stronger political leadership needed to close global gender divide in education – report

Anonymous — Mon, 21 Jan 2019 13:38:01 +0000

̽��ֱ��study, commissioned by the UK Foreign and Commonwealth Office (FCO) and produced by the REAL Centre at the Faculty of Education, ̽��ֱ�� of Cambridge, reveals that the most disadvantaged girls rarely reach high levels of education, beyond primary, that benefit most from national and aid funding. In Nigeria and Pakistan, girls from poor rural households average just one year at school, while rich urban boys enjoy 11 or 12 years of study.

National governments and donor countries must show greater political commitment if global goals on gender equality in education are to be reached, according to the report, 12 Years of Quality Education for All Girls: A Commonwealth Perspective. ̽��ֱ��report will be launched at the Education World Forum, the world’s largest gathering of education and skills ministers, in London on Monday 21 January 2019.

Barriers to access

̽��ֱ��study highlights an array of barriers that prevent girls accessing education, including gender-based violence within and on the way to school, and absenteeism during menstruation because of a lack of availability of sanitary protection. For marginalised girls, cost is also a key barrier in sending girls to school, with poverty leading some girls to have sex with men who provide them with the essentials of secondary schooling that their family cannot afford. Schools must be made “safe spaces” for girls, particularly in areas affected by conflict, say the authors, while cash support for the poorest families may help ease financial pressures and free up daughters to go to school.

Professor Pauline Rose, Director of the REAL Centre and author of the report, said: “Evidence shows us what works to address barriers that marginalised girls face in their access and learning. Much more needs to be done to implement these interventions at far greater scale. It is vital that current political uncertainties do not jeopardise the prioritisation of investment in girls’ education to enable this to happen.”

̽��ֱ��report was commissioned by the Platform for Girls’ Education, co-chaired by the UK Foreign Secretary and Kenyan Cabinet Secretary for Education. ̽��ֱ��platform, a group of 12 influential figures across the Commonwealth, was created after the Commonwealth Heads of Government Meeting (CHOGM) in April 2018 affirmed the importance of 12 years of quality education for all, particularly marginalised girls. Achieving that target by 2030 is one of the UN Sustainable Development Goals signed up to in 2015 by leaders across the globe.

Equality a “distant reality”

̽��ֱ��study finds that, over the past 20 years, considerable progress has been made in increasing access to primary schooling in the 53 countries of the Commonwealth. There are now equal proportions of boys and girls primary enrolled in 31 out of 44 Commonwealth countries with data. But despite this progress, “12 years of schooling remains a distant reality for many of the most disadvantaged girls residing in Commonwealth countries,” the report says. Gender parity in enrolment has sometimes been achieved even though primary schooling is still not universal: in 2017, 137 million primary-and-secondary school aged children were out of school in these countries, approximately half of them girls.

In 15 out of 21 Commonwealth countries with available data, poor rural girls spend no more than five years in school, and so have little chance of making the transition to secondary school. In six countries, they spend only one or two years in education. Children and adolescents affected by conflict are most likely to be out of school, and refugee girls are particularly at risk: they are half as likely as their male counterparts to be in secondary school.

Poor learning in school

Even those children in school are frequently not learning the basics, researchers found. ̽��ֱ��recently launched Human Capital Index shows that girls’ education fares far worse when years in school is adjusted for whether or not children are learning. In 14 out of the 26 countries with data, girls who are in school are learning only for the equivalent of six years or less. ̽��ֱ��picture is likely to be even starker for girls in rural areas and those facing other forms of disadvantage.

Disadvantage starts early, the study says, with many girls denied early years investment that is proven to boost educational achievement later. In eight of 14 Commonwealth countries with data, no more than 40 percent of poor rural girls have access to pre-primary education, and in three out of these eight countries, fewer than 10 percent are enrolled.

Governments should do more to target funding on lower levels of education and marginalised groups, the report argues. In 33 out of 45 Commonwealth countries with data, governments are spending far more on post-primary levels of education than on primary schooling, even though the probability of the most disadvantaged girls reaching these levels of education is extremely low. Of the 35 Commonwealth countries with data on pre-primary spending, 25 governments are spending less than five percent of their education budgets on pre-primary education.

Early years not prioritised

̽��ֱ��same failure to prioritise the early years is seen in education aid spending. Funding for primary education fell from around two thirds in 2002 to under a half (47%) by 2016, and a mere 0.4 percent of education aid to Commonwealth countries was spent on pre-primary education. By contrast, 10 percent is spent on scholarships to allow students from aid-recipient Commonwealth countries to study in donor countries, even though only the most privileged benefit from such schemes.

In addition, only around five percent of total education aid appears to be spent with the main objective of achieving gender equality. ̽��ֱ��UK alone bucks the trend, with all but 2% of education aid targeting gender equality directly or significantly affecting it.

To tackle discrimination and work towards gender equality in education, governments of Commonwealth countries must show visible high-level political commitment backed by resources, the study concludes. Funding towards early childhood education and early learning should be prioritised.

Support for girls at puberty

There must also be steps to address the particular challenges marginalised girls face at puberty, such as provision of sanitary pads in schools, and moves to keep girls safe and secure in school, including providing female staff, secure buildings and door-to-door transport between school and home. More broadly, gender-sensitive teaching practices and materials are needed to ensure discriminatory stereotypes are not enforced, says the study.

̽��ֱ��report sets out three priorities for further action, including “high-level, visible political leadership” towards gender equality in education, backed up by sufficient resources to reach the most marginalised girls. Investment in early years education is also vital, together with making girls’ education a priority in wider national development planning.

For more information, contact: Professor Pauline Rose or Faculty of Education Communications Manager Lucy Ward on lw28@cam.ac.uk

̽��ֱ��poorest girls in many Commonwealth countries spend no more than five years in school, with the global target of 12 years of quality universal education remaining “a distant reality” for many, according to a new report charting global inequality in girls’ education.

It is vital that current political uncertainties do not jeopardise the prioritisation of investment in girls’ education

Pauline Rose

Campaign for Female Education (CAMFED)/Daniel Hayduk

Students in Tanzania.

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UK should invest in global education to improve lives, says report citing Cambridge research

ag236 — Tue, 21 Nov 2017 15:40:21 +0000

̽��ֱ��House of Commons’ International Development Committee (IDC) has published the results of its inquiry into the Department for International Development (DFID)’s work on global education.

̽��ֱ��report, published today, examines DFID’s efforts to ensure the UK is making a significant contribution towards meeting the fourth Sustainable Development Goal agreed by the UN in 2015 –to “ensure inclusive and quality education for all and promote lifelong learning”.

While recognising that DFID is a world leader in promoting education in international development settings, the report calls for increased spending on global education to ensure no child is left behind.

It cites evidence provided by the Faculty of Education’s Research for Equitable Access and Learning (REAL) Centre on the importance of investing in early childhood education and the early years of primary school for benefits in later life.

Drawing on research by the REAL Centre, the IDC’s report states that global spending on pre-primary education is low –DFID’s expenditure on pre-primary education accounts for under 0.6% of its bilateral education budget. Based on the evidence, the report recommends that DFID increases its spending on pre-primary education.

Responding to the evidence, the Minister of State for International Development, the Rt Hon Alistair Burt MP told the inquiry: “It [early childhood education] has not been funded well enough in the past. It has been an area that has been neglected. It does bring the highest returns in the future, and the returns are greatest for the most marginalised children.”

It is widely recognised that getting into school is not enough to ensure children are learning. In many poor countries, children are often spending up to four years in school without being able to read or do basic mathematics.

Drawing further on the REAL Centre’s evidence, the report argues that “it is vital that teachers are equipped with skills to teach in diverse classrooms” to ensure marginalised children –such as children with disabilities—are not excluded from the education process.

̽��ֱ��report has tackled the controversial issue of the role of private schooling, a growing phenomenon in low and lower middle income countries. Research by the REAL Centre shows that “low-fee private schools” are not accessible to the poorest families, leading the IDC report to recommend that DFID should continue to prioritise its spending towards government schools.

DFID is currently updating its education priorities through a “policy refresh”. It is hoped that the messages from the IDC report will help to focus resources on the most marginalised –including the poorest girls, and children with disabilities— and on early years of education, which is most likely to benefit children.

Read the full report here.

Evidence provided by the Research for Equitable Access and Learning (REAL) Centre informs the findings of a cross-party report calling for “significant spending” on early-years education

Early childhood education has not been funded well enough in the past. It has been neglected. It brings the highest returns in the future, and the returns are greatest for the most marginalised children.

Rt Hon Alistair Burt MP, Minister of State for International Development

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Infections during pregnancy may interfere with key genes associated with autism and prenatal brain development

cjb250 — Tue, 21 Mar 2017 09:00:29 +0000

In a study published today in the journal Molecular Psychiatry, researchers at the ̽��ֱ�� of Cyprus, ̽��ֱ�� of Cambridge, ̽��ֱ�� of California, San Diego, and Stanford ̽��ֱ�� used rats and mice to help map the complex biological cascade caused by the mother’s immune response, which may lead to important consequences.

Maternal infections during pregnancy are a known risk factor for abnormal fetal development. Most strikingly, this has been seen during the recent emergence of Zika virus, which led to babies being born with an abnormally small head and brain (known as ‘microcephaly’). In the case of Zika, the virus has its impact by directly attacking fetal brain tissue. However, for most other infections, such as influenza, the infectious agent typically has a more indirect impact on fetal development.

Large population-based studies have previously shown that a variety of maternal infections during pregnancy are associated with small increases in the risk for psychiatric disorders, including autism spectrum disorders and schizophrenia. Other studies have shown that this effect is due not to the infectious agents themselves, but simply due to triggering a strong immune response in a pregnant mother – a phenomenon known as ‘maternal immune activation’.

“It’s important to underscore that the increase in risk is really small – too small to be meaningfully applied to specific individuals, and is only seen in very large studies when examining many thousands of people,” says Dr Michael Lombardo, lead author of the work from the ̽��ֱ�� of Cyprus and the ̽��ֱ�� of Cambridge. “Nevertheless, the biological cascade triggered by this effect is not well understood, particularly in how it may be similar to known biology behind conditions like autism. This was the motivation behind why we did the study.”

To understand how activating a mother’s immune system may affect her child’s brain development, Dr Lombardo and colleagues examined the activity of genes in the brain after injecting pregnant rats and mice with a substance called lipopolysaccharide. This substance contains no infectious agent and thus does not make the mothers sick, but will elicit a strong immune response in the mother, characterized by an increase in levels of cytokines. These are small immune signalling molecules that can have important effects on brain cells and the connections between these cells (known as ‘synapses’ in the fetus’s brain.

̽��ֱ��scientists found that maternal immune activation alters the activity of multiple genes and pathways in the fetus’s brain. Importantly, many of these genes are known to be important in the development of autism and to key brain developmental processes that occur before birth. They believe that these effects may help to explain why maternal immune activation carries a small increased risk for later atypical neurodevelopment.

“ ̽��ֱ��more we understand about how brain development is disrupted by these effects, the higher the chance of finding amenable targets for potential therapeutic intervention or for informing how to prevent such risk from occurring in the first place,” says Dr Tiziano Pramparo, senior author on the work from the ̽��ֱ�� of California, San Diego.

While the effects caused by maternal immune activation are transient, the researchers argue that they may be very potent during fetal development and may cause different characteristics in the individual depending on when it occurs during pregnancy. ̽��ֱ��work underscores the importance of the idea that genes and the environment interact and that their interaction may have important roles in better understanding how risk for neurodevelopmental disorders manifests.

̽��ֱ��research was funded in part by the ̽��ֱ�� of California San Diego Altman Clinical and Translational Research Institute, the National Institutes of Health, the Simons Foundation Autism Research Initiative and the Child Health Research Institute at Stanford ̽��ֱ��.

Reference
Lombardo, MV et al. Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder. Molecular Psychiatry; 21 March 2017; DOI: 10.1038/mp.2017.15

If a mother picks up an infection during pregnancy, her immune system will kick into action to clear the infection – but this self-defence mechanism may also have a small influence how her child’s brain develops in the womb, in ways that are similar to how the brain develops in autism spectrum disorders. Now, an international team of researchers has shown why this may be the case, in a study using rodents to model infection during pregnancy.

It’s important to underscore that the increase in risk is really small.. Nevertheless, the biological cascade triggered by this effect is not well understood, particularly in how it may be similar to known biology behind conditions like autism

Michael Lombardo

Yohann Legrand

Grobidon

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Scientists create artificial mouse ‘embryo’ from stem cells for first time

cjb250 — Thu, 02 Mar 2017 19:00:06 +0000

Understanding the very early stages of embryo development is of interest because this knowledge may help explain why a significant number of human pregnancies fail at this time.

Once a mammalian egg has been fertilised by a sperm, it divides multiple times to generate a small, free-floating ball of stem cells. ̽��ֱ��particular stem cells that will eventually make the future body, the embryonic stem cells (ESCs) cluster together inside the embryo towards one end: this stage of development is known as the blastocyst. ̽��ֱ��other two types of stem cell in the blastocyst are the extra-embryonic trophoblast stem cells (TSCs), which will form the placenta, and primitive endoderm stem cells that will form the so-called yolk sac, ensuring that the foetus’s organs develop properly and providing essential nutrients.

Previous attempts to grow embryo-like structures using only ESCs have had limited success. This is because early embryo development requires the different types of cell to coordinate closely with each other.

However, in a study published today in the journal Science, Cambridge researchers describe how, using a combination of genetically-modified mouse ESCs and TSCs, together with a 3D scaffold known as an extracellular matrix, they were able to grow a structure capable of assembling itself and whose development and architecture very closely resembled the natural embryo.

“Both the embryonic and extra-embryonic cells start to talk to each other and become organised into a structure that looks like and behaves like an embryo,” explains Professor Magdalena Zernicka-Goetz from the Department of Physiology, Development and Neuroscience, who led the research. “It has anatomically correct regions that develop in the right place and at the right time.”

Image: Stem cell-modelled embryo at 96 hours (embryonic (magenta) and extra-embryonic (blue) tissue with surrounding extracellular matrix (cyan)). Credit: Berna Sozen, Zernicka-Goetz Lab, ̽��ֱ�� of Cambridge

Professor Zernicka-Goetz and colleagues found a remarkable degree of communication between the two types of stem cell: in a sense, the cells are telling each other where in the embryo to place themselves.

“We knew that interactions between the different types of stem cell are important for development, but the striking thing that our new work illustrates is that this is a real partnership – these cells truly guide each other,” she says. “Without this partnership, the correct development of shape and form and the timely activity of key biological mechanisms doesn’t take place properly.”

Comparing their artificial ‘embryo’ to a normally-developing embryo, the team was able to show that its development followed the same pattern of development. ̽��ֱ��stem cells organise themselves, with ESCs at one end and TSCs at the other. A cavity opens then up within each cluster before joining together, eventually to become the large, so-called pro-amniotic cavity in which the embryo will develop.

While this artificial embryo closely resembles the real thing, it is unlikely that it would develop further into a healthy foetus, say the researchers. To do so, it would likely need the third form of stem cell, which would allow the development of the yolk sac, which provides nourishment for the embryo and within which a network of blood vessel develops. In addition, the system has not been optimised for the correct development of the placenta.

Professor Zernicka-Goetz recently developed a technique that allows blastocysts to develop in vitro beyond the implantation stage, enabling researchers to analyse for the first time key stages of human embryo development up to 13 days after fertilisation. She believes that this latest development could help them overcome one of the main barriers to human embryo research: a shortage of embryos. Currently, embryos are developed from eggs donated through IVF clinics.

“We think that it will be possible to mimic a lot of the developmental events occurring before 14 days using human embryonic and extra-embryonic stem cells using a similar approach to our technique using mouse stem cells,” she says. “We are very optimistic that this will allow us to study key events of this critical stage of human development without actually having to work on embryos. Knowing how development normally occurs will allow us to understand why it so often goes wrong.”

̽��ֱ��research was largely funded by the Wellcome Trust and the European Research Council.

Dr Andrew Chisholm, Head of Cellular and Developmental Science at Wellcome, said: “This is an elegant study creating a mouse embryo in culture that gives us a glimpse into the very earliest stages of mammalian development. Professor Zernicka-Goetz’s work really shows the importance of basic research in helping us to solve difficult problems for which we don’t have enough evidence for yet. In theory, similar approaches could one day be used to explore early human development, shedding light on the role of the maternal environment in birth defects and health.”

Reference
Harrison, SE et al. Assembly of embryonic and extra-embryonic stem cells to mimic embryogenesis in vitro. Science; 2 March 2017; DOI: 10.1126/science.aal1810

Scientists at the ̽��ֱ�� of Cambridge have managed to create a structure resembling a mouse embryo in culture, using two types of stem cells – the body’s ‘master cells’ – and a 3D scaffold on which they can grow.

We knew that interactions between the different types of stem cell are important for development, but the striking thing that our new work illustrates is that this is a real partnership – these cells truly guide each other

Magdalena Zernicka-Goetz

Sarah Harrison and Gaelle Recher, Zernicka-Goetz Lab, ̽��ֱ�� of Cambridge

Stem cell-modelled embryo at 96 hours (left); Embryo cultured in vitro for 48 hours from the blastocyst stage (right)

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A sewage system that ‘digests’ and ‘cooks’ human waste

lw355 — Fri, 10 Feb 2017 08:40:35 +0000

We are surrounded by friendly and welcoming people, but the language barrier makes communication monumentally challenging. We feel far from the immaculate lawns and gleaming stone of King’s Parade on a summer’s day. Navigating through a cluster of buildings in sweltering heat, even the smell is new. It has a sort of rawness: uncooked meat, unrefined exhaust fumes, untreated sewage.

This isn’t a quick and isolated visit. Instead, it will be the first of many over the next two months to Vingunguti, a densely populated part of Dar Es Salaam, the largest city in Tanzania.

We are here as members of the student-led Cambridge Development Initiative (CDI), which runs several projects in the area. Ours focuses on engineering and, over the past three years, we have been designing and piloting an innovative sewage system to bring cheap and safe sanitation to households that are beyond the reach of the urban infrastructure.

Today we’re helping to lay pipes at shallow depths and gradients to expand our sewage network to 11 new houses, one of the aims on this trip. We’re helped along by the enthusiasm of members of the community, who are keen to have latrines that are connected to a sewage system.

Pit latrines are common here. Not only are they dangerous to empty, and frequently overflow in monsoon season, but these holes in the ground also contribute to the high incidence of water-borne diseases.

But it’s not just about cleaner toilets and streets. CDI’s innovation is the conversion of simplified sewage into useful products – fuel and fertiliser – using a system that has no net waste. ̽��ֱ��sewage flows into a ‘digester’ (designed by a SOWtech, a Cambridge-based company) that generates methane gas, which can then be used by households as a safer and cleaner alternative to charcoal for cooking. ̽��ֱ��effluent output of the digester is then ‘cooked’ using a solar-powered dryer (the EvapoDryer) to make fertiliser for agricultural purposes.

Once the new households are added, CDI will have managed to connect over 400 people to good-quality sanitation infrastructure, moving 1.9 tonnes of waste away from houses every day and generating products for the community that are either used in the households or sold by local entrepreneurs to establish an additional source of income.

On paper, this sounds great. But ensuring that it’s successful and sustainable in practice is tough. There are several case studies – even within Vingunguti – that highlight the dangers of not adequately including the community in projects that directly affect them. With its ethos of participatory development, the CDI model focuses on community organisation, financial ownership and targeted skills and knowledge training. Mobilising the community is a critical first step in the process.

After a community has identified the need for improved sanitation, a Sanitation Users Association (SUA) is established, bringing all the households together and giving them responsibility for managing construction and maintenance. In fact, the householders themselves finance and help to build the network. They are loaned the capital for their latrine construction and they pay this back through a microfinance scheme delivered by a Tanzanian NGO founded and run by a CDI alumnus.

Equally important is the involvement of students from universities in Dar Es Salaam, who are part of a complementary organisation (CDI Tanzania). We work alongside each other every day on all aspects of the project, from designing the network to facilitating community meetings. ̽��ֱ��Tanzanian students offer a unique and valuable perspective on the sanitation issues facing these areas – their insights are crucial to the success of the project.

To be sure that the project has a sustainable impact, we organise educational sessions for community members, delivered by our Tanzanian partners. One focus is health awareness sessions for women and children, covering topics like hand washing and malaria prevention. According to a recent survey, 97% of households agree that the project has improved the health of the community.

One local participant, Mr Mbetela, believes that the dangers of cholera and malaria have now been eliminated as a result of the CDI project. Fatima, another resident, says it has brought peace between neighbours because of the better conditions of the street. Ms Zacharia tells us that the new system has removed the embarrassment she used to feel when using exposed pit latrines.

As we prepare to return to Cambridge, we hear that the municipal water authority is looking to adopt our team’s sewage model, which could lead to 1,000 more people having access to safe, hygienic sanitation facilities in the coming years.

Meanwhile, CDI Cambridge and CDI Tanzania will carry on optimising the digester and cooker. Within 12 months, our goal is for there to be a fully functioning sanitation system, run and maintained by the community, removing human waste from households and turning it into essential products. ̽��ֱ��phrase ‘waste not, want not’ never seemed so apt.

Susannah is studying management at the Judge Business School, and Izhan has just graduated from the Department of Engineering.

Inset image: Susannah Duck and Izhan Khan; credit: Lloyd Mann.

To keep up to date with the latest stories about Cambridge’s engagement with Africa, follow #CamAfrica on Twitter.

Student volunteers Susannah Duck and Izhan Khan describe working with a Tanzanian community to install a system that turns sewage into essential products.

Equally important is the involvement of students from universities in Dar Es Salaam. We work alongside each other every day on all aspects of the project

Susannah Duck and Izhan Khan

Izhan Khan

Dar Es Salaam

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Cambridge study named as People’s Choice for Science magazine’s ‘Breakthrough of the Year 2016’

cjb250 — Thu, 22 Dec 2016 19:00:40 +0000

̽��ֱ��work, led by Professor Magdalena Zernicka-Goetz from the Department of Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge, was the focus of parallel publications earlier this year in the journals Nature Cell Biology and Nature.

Professor Zernicka-Goetz and colleagues developed a new technique that allows embryos to develop in vitro, in the absence of maternal tissue, beyond the implantation stage (when the embryo would normally implant into the womb). This will allow researchers to analyse for the first time key stages of human embryo development up to 13 days after fertilisation. ̽��ֱ��technique could open up new avenues of research aimed at helping improve the chances of success of IVF.

“It’s a wonderful honour to have been given such public recognition for our work,” says Professor Zernicka-Goetz, whose work was funded by Wellcome. “It’s a natural human instinct to be curious about where we come from, but until now, technical hurdles have meant there’s been a huge gap in our understanding of how embryos develop. We hope that our technique will crack open this ‘black box’ and allow us to learn more about our development.”

Dr Marta Shahbazi, one of the co-first authors of the Nature Cell Biology paper, also from Cambridge, adds: “In the same year where scientists have found evidence of gravitational waves, it’s amazing that the public has chosen our work as the most important scientific breakthrough. While our study will help satisfy our scientific curiosity, it is likely to help us better understand what happens in miscarriage and why the success rates for IVF are so low.”

̽��ֱ��work builds on research pioneered by Professor Sir Robert Edwards, for which he was awarded the Nobel Prize in physiology or medicine in 2010. Professor Edwards developed the technique known as in vitro fertilisation (IVF), demonstrating that it was possible to fertilise an egg and culture it in the laboratory for the first six days of development. His work led to the first ever 'test tube baby', Louise Brown.

̽��ֱ��award has been welcomed by Dr Jim Smith, Director of Science at Wellcome: “I’m really pleased to see Magda’s fantastic work recognised by Science, and we send our warmest congratulations to her and her team. In almost doubling the time we can culture human embryos in the lab, she has created completely new opportunities for developmental biologists to understand how we develop. It’s a great achievement, and Wellcome is proud to have supported her ground-breaking work.”

Science - Breakthrough of the Year 2016

Cambridge research that will enable scientists to grow and study embryos in the lab for almost two weeks has been named as the People’s Choice for Science magazine’s ‘Breakthrough of the Year 2016’

It’s a natural human instinct to be curious about where we come from, but until now, technical hurdles have meant there’s been a huge gap in our understanding of how embryos develop

Magdalena Zernicka-Goetz

Magda Human Embryo

Zernick-Goetz lab, ̽��ֱ�� of Cambridge

Imaging a human embryo in the absence of maternal tissues - day 10 (left) and day 11 (right)

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Scientists develop human embryos beyond implantation stage for first time

cjb250 — Wed, 04 May 2016 15:55:47 +0000

Once an egg has been fertilised by a sperm, it divides several times to generate a small, free-floating ball of stem cells. Around day three, these stem cells cluster together inside the embryo towards one side; this stage is known as the blastocyst. ̽��ֱ��blastocyst comprises three cell types: cells that will develop into the future body (which form the ‘epiblast’), cells that will develop into the placenta and allow the embryo to attach to the womb, and cells that form the primitive endoderm that will ensure that the fetus’s organs develop properly and will provide essential nutrients.

This pre-implantation period – so-called as the blastocyst has yet to implant itself into the uterus – has been extensively studied in human embryos using in vitro culture methods. However, on the seventh day of development, the human embryo must implant into the uterus of the mother to survive and to develop further, even though UK law permits embryos to be studied in the laboratory for up to 14 days.

̽��ֱ��failure of an embryo to implant is a major cause of early pregnancy loss and yet the cellular and molecular changes that take place in the human embryo at this stage remain unknown. This is because it is impossible to carry out such studies on embryos developing in the womb, and until now there has been no system to culture human embryos in the laboratory beyond day seven.

Today, in parallel papers in Nature and Nature Cell Biology, two international teams report the development of a technique that allows them to culture human embryos outside the body of the mother for an additional six days, up to day 13 of development. This work builds on previous work by Professor Magdalena Zernicka-Goetz’s team from the ̽��ֱ�� of Cambridge on mouse and was funded by the Wellcome Trust.

Using the technique, the researchers have shown that the reorganisation of the embryo that normally takes place during early post-implantation development can be achieved in the lab given the right culture conditions.

Professor Zernicka-Goetz, who led the UK research and is an author on both studies, says: “Implantation is a milestone in human development as it is from this stage onwards that the embryo really begins to take shape and the overall body plans are decided. It is also the stage of pregnancy at which many developmental defects can become acquired. But until now, it has been impossible to study this in human embryos. This new technique provides us with a unique opportunity to get a deeper understanding of our own development during these crucial stages and help us understand what happens, for example, during miscarriage.”

“Embryo development is an extremely complex process and while our system may not be able to fully reproduce every aspect of this process, it has allowed us to reveal a remarkable self-organising capacity of human blastocysts that was previously unknown,” says Dr Marta Shahbazi one of the co-first authors of the study from the ̽��ֱ�� of Cambridge.

̽��ֱ��researchers established a system for the in vitro culture of human embryos and, using this technique, followed the development of the embryos up to day 13 of development. Immediately following ‘implantation’, the three cell types that comprise the blastocyst reorganise into a new configuration.

“ ̽��ֱ��stem cells in the epiblast that will form the future body have the remarkable ability to self-organise themselves and create a cavity that represent the basic structure of the early post-implantation human embryo,” says Professor Zernicka-Goetz. “Without this cavity, it would be impossible for the embryo to develop further as it is the basis for its future development. It is also a mechanism that we can study using human embryonic stem cells.”

This cavity was previously thought to arise through a process known as apoptosis, or programmed cell death, but using human embryonic stem cell models, the researchers were able to show that in fact cell death is not required for the cavity formation in human embryos.

“This process is similar to what we have recently observed in mouse embryos, despite the significant differences in the structure of post-implantation embryos in these different mammalian species”, says Professor Zernicka-Goetz. “This suggests it may be a fundamental process conserved across many species.”

Dr Simon Fishel, founder and President of CARE Fertility Group, adds: “This is about much more than just understanding the biology of implantation embryo development. Knowledge of these processes could help improve the chances of success of IVF, of which only around one in four attempts are successful.”

This research has been possible thanks to couples that underwent IVF treatment and decided to donate their surplus embryos to advance our understanding of the early phases of post-implantation human development. ̽��ֱ��research was licensed by the UK Human Fertilisation and Embryology Authority.

Left image: At day 10 of embryo development the pluripotent stem cells that will generate the future body self-organise to generate a cavity (the pro-amniotic cavity). This configuration is the basis for the subsequent developmental stages and the formation of the body plan. ̽��ֱ��immunofluorescence image shows a day 10 human embryo cultured in vitro through early post-implantation stages (purple-epiblast, red-nucleus, green-membrane).

Right image: At day 11 of embryo development the pluripotent stem cells that will generate the future body self-organiseto generate a cavity (the pro-amniotic cavity). This configuration is the basis for the subsequent developmental stages and the formation of the body plan. ̽��ֱ��immunofluorescence image shows a day 11 human embryo cultured in vitro through early post-implantation stages (while-epiblast, blue-nucleus, green-membrane).

Reference
Shahbazi, MN et al. Self-organisation of the human embryo in the absence of maternal tissues. Nature Cell Biology; 4 May 2016; DOI: 10.1038/ncb3347

Deglincerti, A et al. Self-organization of the in vitro attached human embryo. Nature; 4 May 2016

A new technique that allows embryos to develop in vitro beyond the implantation stage (when the embryo would normally implant into the womb) has been developed by scientists at the ̽��ֱ�� of Cambridge allowing them to analyse for the first time key stages of human embryo development up to 13 days after fertilisation. ̽��ֱ��technique could open up new avenues of research aimed at helping improve the chances of success of IVF.

Implantation is a milestone in human development as it is from this stage onwards that the embryo really begins to take shape and the overall body plans are decided

Magdalena Zernicka-Goetz

Magda Human Embryo

Zernick-Goetz lab, ̽��ֱ�� of Cambridge

Imaging a human embryo in the absence of maternal tissues - day 10 (left) and day 11 (right)

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Embryo development: Some cells are more equal than others even at four-cell stage

cjb250 — Thu, 24 Mar 2016 16:00:00 +0000

Once an egg has been fertilised by a sperm, it divides several times, becoming a large free-floating ball of stem cells. At first, these stem cells are ‘totipotent’, the state at which a stem cell can divide and grow and produce everything — every single cell of the whole body and the placenta, to attach the embryo to the mother’s womb. ̽��ֱ��stem cells then change to a ‘pluripotent’ state, in which their development is restricted to generating the cells of the whole body, but not the placenta. However, the point during development at which cells begin to show a preference for becoming a specific cell type is unclear.

In studies going back over ten years, Professor Magdalena Zernicka-Goetz and colleagues described how, despite the fact that cells of the four-cell stage embryo retain flexibility, each cell shows a bias in its developmental potential and fate. For example, one of the cells shows a distinct tendency to adopt the pluripotent state while another would eventually give rise to placenta. When this work was originally published, the finding proved controversial in the field as many researchers maintained that even at the four-cell embryo stage, the cells were still identical.

Now, in a study published in the journal Cell, scientists at the ̽��ֱ�� of Cambridge and the European Bioinformatics Institute (EMBL-EBI) suggests that as early as the four-cell embryo stage, the cells are indeed different.

̽��ֱ��researchers used the latest sequencing technologies to model embryo development in mice, looking at the activity of individual genes at a single cell level. They showed that some genes in each of the four cells behaved differently. ̽��ֱ��activity of one gene in particular, Sox21, differed the most between cells; this gene forms part of the ‘pluripotency network’. ̽��ֱ��team found when this gene’s activity was reduced, the activity of a master regulator that directs cells to develop into the placenta increased.

“We know that life starts when a sperm fertilises an egg, but we’re interested in when the important decisions that determine our future development occur,” says Professor Magdalena Zernicka-Goetz from the Department of Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge. “We now know that even as early as the four-stage embryo – just two days after fertilisation – the embryo is being guided in a particular direction and its cells are no longer identical.”

Dr John Marioni of EMBL-EBI, the Wellcome Trust Sanger Institute and the Cancer Research UK Cambridge Institute, adds: “We can make use of powerful sequencing tools to deepen our understanding of the molecular mechanisms that drive development in individual cells. Because of these high-resolution techniques, we are now able to see the genetic and epigenetic signatures that indicate the direction in which early embryonic cells will tend to travel.”

̽��ֱ��research was funded by the Wellcome Trust, the European Molecular Biology Laboratory and Cancer Research UK.

Reference
Heterogeneity in Oct4 and Sox2 Targets Biases Cell Fate in Four-Cell Mouse Embryos. Cell; 24 March 2016. DOI: 10.1016/j.cell.2016.01.047

Genetic ‘signatures’ of early-stage embryos confirm that our development begins to take shape as early as the second day after conception, when we are a mere four cells in size, according to new research led by the ̽��ֱ�� of Cambridge and EMBL-EBI. Although they seem to be identical, the cells of the two day-old embryo are already beginning to display subtle differences.

We now know that even as early as the four-stage embryo – just two days after fertilisation – the embryo is being guided in a particular direction and its cells are no longer identical

Magdalena Zernicka-Goetz

Zernick-Goetz lab, ̽��ֱ�� of Cambridge

4-cell stage embryo

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