̽��ֱ�� of Cambridge - Margherita Turco

Surviving birth

lw355 — Thu, 10 Dec 2020 09:00:28 +0000

Researchers at one of the busiest maternity hospitals in the world aim to help more women survive complications giving birth.

Eight Cambridge researchers awarded major European starter grants

cjb250 — Tue, 03 Sep 2019 13:35:55 +0000

̽��ֱ��European Research Council (ERC) Starting Grants have been awarded to 408 researchers from across Europe. ̽��ֱ��awards will help individual researchers to build their own teams and conduct world-leading research across all disciplines, creating an estimated 2,500 jobs for postdoctoral fellows, PhD students and other staff at the host institutions.

̽��ֱ��successful Cambridge researchers are:

Roland Bauerschmidt - Renormalisation, dynamics, and hyperbolic symmetry
Quentin Berthet - Computational Trade-offs and Algorithms in Statistics
Felix Deschler - Twisted Perovskites: Control of Spin and Chirality in Highly-luminescent Metal-halide Perovskites
Lorenzo Di Michele - A DNA NANOtechology toolkit for artificial CELL design
Louise Hirst - Gliding epitaxy for inorganic space-power sheets
Sertac Sehlikoglu - Imaginative Landscapes of Islamist Politics Across the Balkan-to-Bengal Complex
Blake Sherwin - CMB Lensing at Sub-Percent Precision: A New Probe of Cosmology and Fundamental Physics
Margherita Turco - Human Placental Development and the Uterine Microenvironment

Commenting on the awards, Dr Peter Hedges, Head of the ̽��ֱ�� Research Office at the ̽��ֱ�� of Cambridge, said: “ ̽��ֱ��success of UK researchers, and in particular Cambridge researchers, demonstrates the world-leading position that our country holds in research and innovation. This is a position we have will have to fight hard to maintain in the face of competition from other nations across Europe, the USA and China.

“Six of our successful researchers are non-UK nationals, showing once again that Cambridge has the ability to attract the very best talent from around the world to carry out research at its world class facilities.”

̽��ֱ��ERC-funded research will be carried out in 24 countries, with institutions from Germany (73), the UK (64) and the Netherlands (53) to host the highest number of projects. ̽��ֱ��grants, worth in total €621 million (£560 million), are part of the EU Research and Innovation programme, Horizon 2020.

Carlos Moedas, European Commissioner for Research, Science and Innovation, said: “Researchers need freedom and support to follow their scientific curiosity if we are to find answers to the most difficult challenges of our age and our future. This is the strength of the grants that the EU provides through the European Research Council: an opportunity for outstanding scientists to pursue their most daring ideas.”

President of the ERC, Professor Jean-Pierre Bourguignon, added: “In this year’s ERC Starting Grant competition, early-career researchers of 51 nationalities are among the winners – a record. It reminds us that science knows no borders and that talent is to be found everywhere. It is essential that, for its future successful development, the European Union keeps attracting and supporting outstanding researchers from around the world. At the ERC we are proud to contribute to this goal by supporting some of the most daring creative scientific talent.”

Eight Cambridge researchers are among the latest recipients of European Union awards given to early-career researchers from over 50 countries.

Six of our successful researchers are non-UK nationals, showing once again that Cambridge has the ability to attract the very best talent from around the world to carry out research at its world class facilities

Peter Hedges

Géry PARENT

Naturally-occurring perovskite

Researcher profile: Dr Margherita Turco

Among this year’s successful awardees is Dr Margherita Turco from Cambridge’s Centre for Trophoblast Research (CTR).

Margherita began her career studying the development of embryos in domestic animals during her studies for Veterinary Biotechnology at the ̽��ֱ�� of Bologna, in Italy. During her PhD in Molecular Medicine at the European Institute of Oncology in Milano, she became interested in how early cell lineage decisions are made and began using various stem cells models to address this question.

This led Margherita to come to Cambridge in 2012 to carry out her postdoctoral work on human trophoblast stem cells at the CTR. Her goal is to understand how the human placenta grows and develops during pregnancy.

“ ̽��ֱ��placenta is a remarkable organ that is formed early in pregnancy. It plays the crucial role of nourishing and protecting the baby throughout its development before birth,” she says. However, there is a lot that can go wrong during this period.

“Complications occurring during pregnancy, such as pre-eclampsia, fetal growth restriction, stillbirth, miscarriage and premature birth, are principally due to defective placental function. These conditions, which collectively affect around one in five pregnancies, can pose a risk to both the baby and mother’s health. Understanding early placental development is the key to understanding successful pregnancy.”

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‘Mini-placentas’ could provide a model for early pregnancy

cjb250 — Wed, 28 Nov 2018 18:00:49 +0000

Many pregnancies fail because the embryo does not implant correctly into the lining of the womb (uterus) and fails to form a placental attachment to the mother. Yet, because of the complexities of studying this early period of our development, very little is understood about what is happening normally and what can go wrong. Animals are too dissimilar to humans to provide a good model of placental development and implantation.

“ ̽��ֱ��placenta is absolutely essential for supporting the baby as it grows inside the mother,” says Dr Margherita Turco, the study’s first author, from the Departments of Pathology and Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge. “When it doesn’t function properly, it can result in serious problems, from pre-eclampsia to miscarriage, with immediate and lifelong consequences for both mother and child. But our knowledge of this important organ is very limited because of a lack of good experimental models.”

Efforts to grow human placental cells started over 30 years ago in the Pathology department where Professors Ashley Moffett and Charlie Loke were studying cellular events in the first few weeks of pregnancy. With their chief technician, Lucy Gardner, they found ways to isolate and characterise placental trophoblast cells. These techniques, combined with the organoid culture system, enabled the generation of miniature functional models of the early placenta – or ‘mini-placentas’.

In the past few years, a new field of research has blossomed that uses these organoids – often referred to as ‘mini-organs’ – enabling insights into human biology and disease. At the ̽��ֱ�� of Cambridge, one of the world leaders in organoid research, scientists are using organoid cultures to grow everything from ‘mini-brains’ to ‘mini-livers’ to ‘mini-lungs’.

In a study funded by Wellcome and the Centre for Trophoblast Research, the Cambridge team was able to grow organoids using cells from villi – tiny frond-like structures – taken from placental tissue. These trophoblast organoids are able to survive long-term, are genetically stable and organise into villous-like structures that secrete essential proteins and hormones that would affect the mother’s metabolism during the pregnancy. Further analysis showed that the organoids closely resemble normal first-trimester placentas. In fact, the organoids so closely model the early placenta that they are able to record a positive response on an over-the-counter pregnancy test.

Professor Graham Burton, a co-author and Director of the Centre for Trophoblast Research, which last year celebrated its tenth anniversary, says: “These ‘mini-placentas’ build on decades of research and we believe they will transform work in this field. They will play an important role in helping us investigate events that happen during the earliest stages of pregnancy and yet have profound consequences for the life-long health of the mother and her offspring. ̽��ֱ��placenta supplies all the oxygen and nutrients essential for growth of the fetus, and if it fails to develop properly the pregnancy can sadly end with a low birthweight baby or even a stillbirth.”

In addition, the organoids may shed light on other mysteries surrounding the relationships between the placenta, the uterus and the fetus: why, for example, is the placenta able to prevent some infections passing from the mother’s blood to the fetus while others, such as Zika virus, are able to pass through this barrier? ̽��ֱ��organoids may also be used for screening the safety of drugs to be used in early pregnancy, to understand how chromosomal abnormalities may perturb normal development, and possibly even provide stem cell therapies for failing pregnancies.

Last year, the same team supported by Cambridge’s Centre for Trophoblast Research reported growing miniature functional models of the uterine lining.

“Now that we’ve developed organoid models of both sides of the interface – maternal tissue and placental tissue – we can start to look at how these two sides talk to each other,” adds Professor Ashley Moffett.

Professor Moffett also co-directed a recent study published in Nature that used genomics and bioinformatics approaches to map over 70,000 single cells at the junction of the uterus and placenta. This study revealed how the cells talk to each other to modify the immune response and enable the pregnancy, presenting new and unexpected cell states in the uterus and placenta, and showing which genes are switched on in each cell.

References

Turco, MY et al. Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature; 28 Nov 2018; DOI: 10.1038/s41586-018-0753-3

Vento-Tormo, R, et al. Single-cell reconstruction of the early maternal–fetal interface in humans. Nature; 14 Nov 2018; DOI: 10.1038/s41586-018-0698-6

Researchers say that new ‘mini-placentas’ – a cellular model of the early stages of the placenta – could provide a window into early pregnancy and help transform our understanding of reproductive disorders. Details of this new research are published today in the journal Nature.

̽��ֱ��placenta is absolutely essential for supporting the baby as it grows inside the mother. When it doesn’t function properly, it can result in serious problems

Margherita Turco

Title: Image reproduced with the permission of SPD Swiss Precision Diagnostics GmbH (SPD)

Researcher profile: Dr Margherita Turco

Dr Margherita Turco began her career studying the development of embryos in domestic animals during her studies for Veterinary Biotechnology at the ̽��ֱ�� of Bologna, in Italy. During her PhD in Molecular Medicine at the European Institute of Oncology in Milano, she became interested in how early cell lineage decisions are made and began using various stem cells models to address this question.

This led Margherita to come to Cambridge in 2012 to carry out her postdoctoral work on human trophoblast stem cells at Cambridge’s Centre for Trophoblast Research (CTR), during which time she was awarded a Marie Curie Fellowship. She now has a Royal Society Dorothy Hodgkin Fellowship that has enabled her to build up her own research group.

Margherita’s goal is to understand how the human placenta grows and develops during pregnancy.

There is a lot that can go wrong during this period, however.

Human placental development has been a ‘black box’ for ethical and practical reasons. “ ̽��ֱ��lack of reliable experimental models that accurately mimic how placental cells behave has hindered our ability to ask even quite basic questions,” she says.

To address this issue, Margherita was funded by the CTR to develop models of the human placenta.. Her mentors have included Professors Ashley Moffett and Graham Burton from the Centre, and Dr Myriam Hemberger from the Babraham Institute, bringing together different a wide range of expertise to this challenging project.

Margherita uses a type of model known as an ‘organoid’ and has now managed to generate organoid models from both the mother’s uterus and the placenta, the two sides of the maternal-fetal interface.

“As their name suggests, organoids are essentially mini-organs grown in the laboratory that preserve the normal cellular architecture and function,” she says. “They have proved to be powerful tools in investigating development and biological functions in many other organ systems – the heart, gut, liver, kidney and brain. They can also be used for screening drugs and studying how pathogens affect tissues. I believe they will be equally transformative for the investigation of early pregnancy and the origin of later complications.”

Cambridge has been the ideal place for Margherita to carry out her research because of the unique concentration of placental and stem cell biologists within the CTR.

“There is no other place in the world with such a combination of skills, knowledge and resources,” she says.

“I hope to be able to uncover the mysterious events that occur early in human pregnancy that previously were not possible to study. In the longer term, I hope this will alleviate the suffering experienced by couples affected by infertility or complications of pregnancy.”

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Miniature ‘womb lining’ grown in lab could reveal secrets of menstrual cycle and early pregnancy

cjb250 — Mon, 10 Apr 2017 15:30:19 +0000

̽��ֱ��mucosal lining inside the uterus is called the endometrium. Over the course of the menstrual cycle, its composition changes, becoming thicker and rich with blood vessels in preparation for pregnancy, but if the woman does not conceive, the uterus sheds this tissue, causing the woman’s period.

A team from the Centre for Trophoblast Research, which this year celebrates its tenth anniversary, was able to grow the organoids in culture from cells derived from endometrial tissue and maintain the organoids in culture for several months, faithfully reproducing the genetic signature of the endometrium – in other words, the pattern of activity of genes in the lining of the uterus. They also demonstrated that the organoids respond to female sex hormones and early pregnancy signals, secreting what are collectively known as ‘uterine milk’ proteins that nourish the embryo during the first months of pregnancy.

̽��ֱ��findings of the study, funded by the Medical Research Council, the Wellcome Trust and the Centre for Trophoblast Research, are published today in the journal Nature Cell Biology.

̽��ֱ��organoids are capable of generating both secretory (red) and epithelial (cyan) cells of the uterus. Image: Centre for Trophoblast Research

“These organoids provide a major step forward in investigating the changes that occur during the menstrual cycle and events during early pregnancy when the placenta is established,” says Dr Margherita Turco, the study’s first author. “These events are impossible to capture in a woman, so until now we have had to rely on animal studies.”

“Events in early pregnancy lay the foundations for a successful birth, and our new technique should provide a window into this events,” adds Professor Graham Burton, Director of the Centre for Trophoblast Research, and joint senior author with Ashley Moffett of the study. “There’s increasing evidence that complications of pregnancy, such as restricted growth of the fetus, stillbirth and pre-eclampsia – which appear later in pregnancy – have their origins around the time of implantation, when the placenta begins to develop.”

Research in animal species such as mice and sheep has shown that factors secreted by the endometrial glands are critical for enabling a developing fertilised egg (known as the ‘conceptus’) to implant into the wall of the uterus. There is also strong evidence that the conceptus sends signals to the endometrial glands that then stimulate the development of the placenta. In this way, the conceptus is able to stimulate its own development through a ‘dialogue’ with the mother; if it fails, the result is loss of the pregnancy or severe growth restriction of the fetus.

Professor Burton and colleagues believe that using the organoids will allow them to investigate in greater detail how the conceptus communicates with the glands, identifying the full repertoire of factors released in response and testing their effects on placental tissues. His team will be collaborating with the Bourn Hall Clinic – a fertility clinic near Cambridge – to investigate whether parts of this circuitry are impaired or deficient in women experiencing difficulty in conceiving, and if so to devise potential new treatments.

̽��ֱ��technique also enables the researchers to grow organoids from endometrial cancer cells. As proof-of-principle, this will allow them to model and understand diseases of the endometrium, including cancer of the uterus and endometriosis.

Organoid cultures have proven to be powerful tools for investigating the behaviour of other organ systems. Members of the Centre for Trophoblast Research are confident that their new advance will provide a much-needed window on events during the earliest stages of pregnancy, when the conceptus and mother first physically interact.

Reference
Turco, MY et al. Long-term, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nature Cell Biology; 10 April 2017; DOI: 10.1038/ncb3516

Scientists at the ̽��ֱ�� of Cambridge have succeeded in growing miniature functional models of the lining of the womb (uterus) in culture. These organoids, as they are known, could provide new insights into the early stages of pregnancy and conditions such as endometriosis, a painful condition that affects as many as two million women in the UK.

These organoids provide a major step forward in investigating the changes that occur during the menstrual cycle and events during early pregnancy

Margherita Turco

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