̽��ֱ�� of Cambridge - Ashley Moffett

Cambridge talent recognised in 2025 New Year Honours

ps748 — Mon, 30 Dec 2024 22:30:00 +0000

Former ̽��ֱ�� of Cambridge Vice-Chancellor Professor Sir Leszek Borysiewicz, an Honorary Fellow of Wolfson College, Homerton College and St Edmund's College, is made Knight Grand Cross (GBE) for services to cancer research, clinical research, medicine and to charities.

Professor Ijeoma Uchegbu, who has been President of Wolfson College since October 2024, becomes a Dame (DBE) for services to chemical sciences and inclusion and diversity. Professor Uchegbu is a renowned expert in the field of pharmaceutical science and was most recently Professor of Pharmaceutical Nanoscience at ̽��ֱ�� College London. Her research has focussed on methods that can be used to help drugs reach their target more effectively and reduce the likelihood of uncomfortable side effects. While at UCL she spearheaded a project to improve outcomes for both staff and students from under-represented ethnic groups. She is is a Fellow of the Academy of Medical Sciences and an Honorary Fellow of the Royal Society of Chemistry.

She said: “I’m absolutely thrilled. I wouldn’t say I’m humbled – I know people say that, but when I saw the letter at the Porters’ Lodge what I felt was an overwhelming sense of gratitude and pride. In my wildest dreams I never believed I would get such an award.”

Professor Ashley Moffet, Professor of Reproductive Immunology, is made Companion of the Most Distinguished Order of Saint Michael and Saint George (CMG) for services to reproductive health. A Fellow of King's College, she is the foremost international authority on the immunology of human reproduction and her work on genetic research has helped explain high rates of pre-eclampsia and maternal mortality in Ugandan populations. She is a Fellow of both the Academy of Medical Sciences and the Royal College of Obstetricians and Gynaecologists.

She said: "I am delighted by this honour that is a tribute to the hard work and dedication of my many colleagues both here in Cambridge and in Uganda who are working together so tirelessly to support women in the field of maternal health."

Professor Gilly Carr is Professor of Conflict Archaeology and Holocaust Heritage and receives an OBE for services to Holocaust research and education. Professor Carr, a Fellow of St Catharine's College, is a member of both the UK delegation of the International Holocaust Remembrance Alliance (IHRA) and the academic advisory board for the UK Holocaust Memorial Centre. Professor Carr has a particular research interest in wartime incarceration, internment and imprisonment. 2024 saw the publication of her latest book, 'A Materiality of Internment', which drew on over 15 years of research and interviews with more than 65 former internees.

She said: “I am absolutely thrilled for my research and teaching to be recognised in this way. I've been working hard on behalf of victims of Nazism and the Holocaust for 15 years and for this to be seen as nationally important and worthwhile encourages me to continue my work with vigour.”

Professor Rachel Oliver, who also receives an OBE, is a materials engineer, inventor and commercial spinout founder. A Fellow of Robinson College, she is currently Director of the Cambridge Centre for Gallium Nitride and Chief Scientific Officer of Poro Technologies Ltd (Porotech). Her research is in understanding and engineering the small-scale structure of semiconductor materials to enable new technologies to develop. Professor Oliver is a Fellow of the Royal Society of Engineering and is a passionate advocate for equality, diversity and inclusion in science and engineering.

She said: “I am delighted to receive this honour and it is vital that I acknowledge the fabulous teams that I work with both in the ̽��ֱ�� of Cambridge and at Porotech, a company that spun out from my research group. I hope I can encourage more people to get involved in semiconductors in the UK. ̽��ֱ��semiconductor ecosystem has been an exciting place to work throughout my career, but never more so than right now, with both research and industry rapidly growing and stepping up to address some of the most pressing challenges we face.”

Dr James Biddulph, former headteacher of the ̽��ֱ�� of Cambridge Primary School, has been awarded an MBE for services to education. Dr Biddulph was the inaugural headteacher of the school from 2015 until 2023, and under his leadership it attained an Outstanding Ofsted rating in 2018.

Eleanor Sharpston KC, an Emeritus Fellow of King's College, has been made Dame Commander of the Order of St Michael and St George (DCMG) for services to Justice and to the Education of Law in the UK and Europe. Dame Eleanor has combined a career as a barrister (specialising in European Union and European Convention on Human Rights law) with an academic career first at ̽��ֱ�� College London and then at the ̽��ֱ�� of Cambridge where she continues as a Yorke Distinguished Visiting Fellow at the Law Faculty. She was also Arthur Goodhart Visiting Professor in Legal Science from 2023 to 2024.

Academics and staff at both the ̽��ֱ�� of Cambridge and Colleges feature in the 2025 list, which recognises the achievements and service of people across the UK.

̽��ֱ��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.

Yes

‘Mini-placentas’ help scientists understand the causes of pre-eclampsia and pregnancy disorders

cjb250 — Wed, 17 Jan 2024 16:00:37 +0000

̽��ֱ��study, published today in Cell Stem Cell, shows that it is possible to experiment on a developing human placenta, rather than merely observe specimens, in order to study major disorders of pregnancy.

Successful pregnancy depends on the development of the placenta in the first few weeks of gestation. During this period, the placenta implants itself into the endometrium – the mucosal lining of the mother’s uterus.

Interactions between the cells of the endometrium and the cells of the placenta are critical to whether a pregnancy is successful. In particular, these interactions are essential to increase the maternal blood supply to the placenta, necessary for fetal growth and development.

When these interactions do not work properly, they can lead to complications, such as pre-eclampsia, a condition that causes high blood pressure during pregnancy. Pre-eclampsia occurs in around six in 100 first pregnancies and can put at risk the health of both the mother and the baby.

Professor Ashley Moffett from the Department of Pathology at the ̽��ֱ�� of Cambridge said: “Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study – the period after implantation, when the placenta embeds itself into the endometrium, is often described as a ‘black box of human development’.

“Over the past few years, many scientists – including several at Cambridge – have developed embryo-like models to help us understand early pre-implantation development. But further development is impeded because we understand so little about the interactions between the placenta and the uterus.”

Professor Moffett and colleagues at the Friedrich Miescher Institute, Switzerland, and the Wellcome Sanger Institute, Cambridge, have used ‘mini-placentas’ – a cellular model of the early stages of the placenta – to provide a window into early pregnancy and help improve our understanding of reproductive disorders. Known as ‘trophoblast organoids’, these are grown from placenta cells and model the early placenta so closely that they have previously been shown to record a positive response on an over-the-counter pregnancy test.

In previous work, Professor Moffett and colleagues identified genes that increase the risk of or protect against conditions such as pre-eclampsia. These highlighted the important role of immune cells uniquely found in the uterus, known as ‘uterine natural killer cells’, which cluster in the lining of the womb at the site where the placenta implants. These cells mediate the interactions between the endometrium and the cells of the placenta.

In their new study, her team applied proteins secreted by the uterine natural killer cells to the trophoblast organoids so that they could mimic the conditions where the placenta implants itself. They identified particular proteins that were crucial to helping the organoids develop. These proteins will contribute to successful implantation, allowing the placenta to invade the uterus and transform the mother’s arteries.

“This is the only time that we know of where a normal cell invades and transforms an artery, and these cells are coming from another individual, the baby,” said Professor Moffett, who is also a Fellow at King’s College, Cambridge.

“If the cells aren’t able to invade properly, the arteries in the womb don’t open up and so the placenta – and therefore the baby – are starved of nutrients and oxygen. That's why you get problems later on in pregnancy, when there just isn't enough blood to feed the baby and it either dies or is very tiny.”

̽��ֱ��researchers also found several genes that regulate blood flow and help with this implantation, which Professor Moffett says provide pointers for future research to better understand pre-eclampsia and similar disorders.

Dr Margherita Turco, from the Friedrich Miescher Institute in Switzerland and co-lead of this work, added: “Despite affecting millions of women a year worldwide, we still understand very little about pre-eclampsia. Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it – to predict it and prevent it – we have to look at what's happening in the first few weeks.

“Using ‘mini-placentas’, we can do just that, providing clues as to how and why pre-eclampsia occurs. This has helped us unpick some of the key processes that we should now focus on far more. It shows the power of basic science in helping us understand our fundamental biology, something that we hope will one day make a major difference to the health of mothers and their babies.”

̽��ֱ��research was supported by Wellcome, the Royal Society, European Research Council and Medical Research Council.

Reference
Li, Q et al. Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy. Cell Stem Cell; 17 Jan 2024; DOI: doi.org/10.1016/j.stem.2023.12.013

Volunteers wanted for women's health study

̽��ֱ�� of Cambridge researchers at Addenbrooke’s Hospital are looking for volunteers who are planning their first pregnancy, to take part in a new study focussing on pregnancy and women’s long-term health (the POPPY study).

̽��ֱ��POPPY study aims to understand why some women develop pre-eclampsia and other placental complications and why these conditions have an adverse effect on women’s future heart health.

If you are aged 18-45 years and are planning your first pregnancy, you may be eligible to participate. We are also looking for similar aged volunteers who are not actively planning a pregnancy, for a control group.

Reimbursement is provided for time, inconvenience and travel.

To find out more, please visit the POPPY study website or email the POPPY study team.

18 January 2024

Scientists have grown ‘mini-placentas’ in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb – findings that could help scientists better understand and, in future, potentially treat pre-eclampsia.

Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study.

Ashley Moffett

Friedrich Miescher Institute/ ̽��ֱ�� of Cambridge

Placental organoid (circle in the centre). Trophoblast cells are invading out of the organoid, mimicking placental cells invading the uterus in the early weeks of pregnancy.

Yes

Cell mapping and ‘mini placentas’ give new insights into human pregnancy

jg533 — Wed, 29 Mar 2023 16:12:59 +0000

Researchers from the ̽��ֱ�� of Cambridge, the Wellcome Sanger Institute, the Friedrich Miescher Institute for Biomedical Research (FMI), Switzerland, EMBL’s European Bioinformatics Institute (EMBL-EBI), and collaborators, have created an in-depth picture of how the placenta develops and communicates with the uterus.

̽��ֱ��study, published today in the journal Nature, is part of the Human Cell Atlas initiative to map every cell type in the human body. It informs and enables the development of experimental models of the human placenta.

"For the first time, we have been able to draw the full picture of how the placenta develops and describe in detail the cells involved in each of the crucial steps. This new level of insight can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide,” said Anna Arutyunyan, co-first author at the ̽��ֱ�� of Cambridge and Wellcome Sanger Institute.

̽��ֱ��placenta is a temporary organ built by the foetus that facilitates vital functions such as foetal nutrition, oxygen and gas exchange, and protects against infections. ̽��ֱ��formation and embedding of the placenta into the uterus, known as placentation, is crucial for a successful pregnancy.

Understanding normal and disordered placentation at a molecular level can help answer questions about poorly understood disorders including miscarriage, stillbirth, and pre-eclampsia. In the UK, mild pre-eclampsia affects up to six per cent of pregnancies. Severe cases are rarer, developing in about one to two per cent of pregnancies.

Many of the processes in pregnancy are not fully understood, despite pregnancy disorders causing illness and death worldwide. This is partly due to the process of placentation being difficult to study in humans, and while animal studies are useful, they have limitations due to physiological differences.

During its development, the placenta forms tree-like structures that attach to the uterus, and the outer layer of cells, called trophoblast, migrate through the uterine wall, transforming the maternal blood vessels to establish a supply line for oxygen and nutrients.

In the new study, scientists built on previous work investigating the early stages of pregnancy, to capture the process of placental development in unprecedented detail. Cutting-edge genomic techniques allowed them to see all of the cell types involved and how trophoblast cells communicate with the maternal uterine environment around them.

̽��ֱ��team uncovered the full trajectory of trophoblast development, suggesting what could go wrong in disease and describing the involvement of multiple populations of cells, such as maternal immune and vascular cells.

"This research is unique as it was possible to use rare historical samples that encompassed all the stages of placentation occurring deep inside the uterus. We are glad to have created this open-access cell atlas to ensure that the scientific community can use our research to inform future studies,” said Professor Ashley Moffett, co-senior author at the ̽��ֱ�� of Cambridge's Department of Pathology.

They also compared these results to placental trophoblast organoids, sometimes called ‘mini-placentas’, that are grown in the lab. They found that most of the cells identified in the tissue samples can be seen in these organoid models. Some later populations of trophoblast are not seen and are likely to form in the uterus only after receiving signals from maternal cells.

̽��ֱ��team focussed on the role of one understudied population of maternal immune cells known as macrophages. They also discovered that other maternal uterine cells release communication signals that regulate placental growth.

̽��ֱ��insights from this research can start to piece together the unknowns about this stage of pregnancy. ̽��ֱ��new understanding will help in the development of effective lab models to study placental development and facilitate new ways to diagnose, prevent, and treat pregnancy disorders.

This research was funded by Wellcome, ̽��ֱ��Royal Society, and the European Research Council.

Reference

Arutyunyan, A et al: 'Spatial multiomics map of trophoblast development in early pregnancy.' March 2023, Nature. DOI: 10.1038/s41586-023-05869-0

Adapted from a press release by the Wellcome Sanger Institute.

Researchers have mapped the complete trajectory of placental development, helping shed new light on why pregnancy disorders happen.

This can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide.

Anna Arutyunyan

Kenny Roberts, Wellcome Sanger Institute

Cells of the placenta

̽��ֱ��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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Licence type:

Attribution

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.

Cambridge Science Festival returns for milestone 25th year

Anonymous — Fri, 25 Jan 2019 15:48:27 +0000

Celebrating its 25th year, the Festival runs for two weeks from 11-24 March and explores the theme of ‘discoveries’. An impressive line-up of acclaimed scientists includes microscopist Professor Dame Pratibha Gai, Astronomer Royal Professor Lord Martin Rees, 2018 Nobel prize winner Sir Gregory Winter, geneticist Dr Giles Yeo, statistician Professor David Spiegelhalter, engineer Dr Hugh Hunt, marine biologist and author Helen Scales, THIS Institute Director Professor Mary Dixon-Woods, futurist Mark Stevenson, and science presenter Steve Mould.

̽��ֱ��full programme is teeming with events ranging from debates, talks, exhibitions, workshops and interactive activities to films, comedy and performances, held in lecture theatres, museums, cafes and galleries around Cambridge. There are events for all ages and most are free.
With so many events on offer, audiences will be spoilt for choice. Some of the biggest events in week one include:

Is technology making us miserable? (11 March). Virtually every interaction we have is mediated through technology. Despite being ‘always-on’, are we any better off? Are we better connected? Or is technology making us miserable?
Putting radioactivity in perspective (12 March). Following a renewal of electricity generated by nuclear power, Professors Ian Farnan and Gerry Thomas, Imperial College London, discuss radioactivity in the natural world and the outcomes of decades of study on the health effects of radiation. Could these research outcomes reset attitudes towards radiation and the risks?
̽��ֱ��universe of black holes (13 March). Christopher Reynolds, Plumian Professor of Astronomy, describes how future research into black holes may yet again change our view of reality.
̽��ֱ��long-term perspective of climate change (14 March). Professors Ulf Büntgen, Mike Hulme, Christine Lane, Hans W Linderholm, Clive Oppenheimer, Baskar Vira, and Paul J Krusic discuss how we investigate past climate and the challenges we face in applying this to the policy-making process.
Catalytic activation of renewable resources to make polymers and fuels (15 March). Professor Charlotte Williams, ̽��ֱ�� of Oxford, discusses the development of catalysts able to transform carbon dioxide into methanol, a process which may deliver more sustainable liquid transport fuels in the future.
Does the mother ever reject the fetus? (15 March). Professor Ashley Moffett discusses fetal rejection and explores new discoveries that show that there are multiple mechanisms to ensure there is a peaceful environment in the uterus, where the placenta is allowed to grow and develop to support the fetus.

Top picks for the second week include:

Cambridge gravity lecture: Sir Gregory Winter (18 March). Sir Gregory is a molecular biologist and 2018 Nobel Laureate best known for his work on developing technologies to make therapeutic monoclonal antibodies. His research has led to antibody therapies for cancer, rheumatoid arthritis and multiple sclerosis.
Discoveries leading to new treatments for dementia (18 March). Professor of Clinical Neurosciences and Associate Director of the UK Dementia Research Institute, Giovanna Mallucci discusses how new research leading to insights into dementia and degenerative brain diseases may lead to new treatments.
Improving quality and safety in healthcare (19 March). THIS Institute Director Professor Mary Dixon-Woods looks at the challenges to improving quality and safety in healthcare and considers why it’s so hard to answer the question: Does quality improvement actually improve quality? With Dr Fiona Godlee, Editor in Chief of ̽��ֱ��BMJ.
Immunology: the future of medicine? (19 March) Professor Clare Bryant and a panel of Cambridge immunologists discuss how understanding disease triggers may enable entirely new approaches to treating and potentially preventing disease.
Polar ocean: the dead end of plastic debris (19 March). An estimated 80% of all the litter in our oceans is plastic, and a significant concentration of plastics debris is found in both polar oceans. ̽��ֱ��impact of this debris on the sensitive polar ecosystem could be profound. Pelagic marine ecologist Dr Clara Manno, British Antarctic Survey, explores the current research and existing situation in the polar regions.
Reluctant futurist (19 March). Old models for healthcare, education, food production, energy supply and government are creaking under the weight of modern challenges. Futurist Mark Stevenson looks at the next 30 years and asks, how can we re-invent ourselves for the future?
Adolescent mental health: resilience after childhood adversity (20 March). Adolescence is characterised by huge physiological changes as well as a rapid rise in mental health disorders. Around 45% of adolescent mental health problems are caused by childhood difficulties but fortunately not all who experience difficulties develop mental health disorders. Dr Anne-Laura van Harmelen discusses mechanisms that may help adolescents with a history of childhood difficulty to become more resilient.
Making algorithms trustworthy (21 March). Increasingly, algorithms are being used to make judgements about sensitive parts of our lives. How do we check how their conclusions were arrived at, and if they are valid and fair? Professor David Spiegelhalter looks at efforts to make algorithms transparent and trustworthy, using systems that make predictions for people with cancer as an example.
On the future: prospects for humanity (22 March). Professor Lord Martin Rees argues that humanity’s prospects on Earth and in space depend on our taking a different approach to planning for tomorrow.

This year’s Cambridge Science Festival also celebrates significant milestones in science, including the 200th anniversary of Cambridge Philosophical Society, Cambridge’s oldest scientific society, and 150 years since the publication of the modern Periodic Table.

Speaking ahead of the Festival, Dr Lucinda Spokes, Festival Manager, said: “We are tremendously proud of this year’s programme due to the variety of events and the calibre of our speakers from a range of institutions and industries.

“Alongside the meatier topics we have an array of events for all ages and interests across both weekends. We have everything from the science of perfumery and how your mood affects your taste, to a science version of 'Would I Lie to You?'

“One of my personal top picks are the open days at the various institutes and departments based at the West Cambridge site on Saturday 23 March. As always, the site is hosting some truly fascinating events, everything from the future of construction and how to make Alexa smarter, to how nanotechnology is opening up new routes in healthcare, and state-of-the-art approaches to low-cost solar energy and high-efficiency lighting solutions.

“A Festival of this magnitude would not be possible without the help from many people; we thank all our scientists, supporters, partners and sponsors, without whom the Festival would not happen. Most of all, we thank the audiences – there are more than 60,000 visits to the Festival events every year. We very much look forward to welcoming everyone from all ages to join us in March to explore the fabulous world of science.”

You can download the full programme here.

Bookings open on Monday 11 February at 11am.

This year’s Festival sponsors and partners are Cambridge ̽��ֱ�� Press, AstraZeneca, MedImmune, Illumina, TTP Group, Science AAAS, Anglia Ruskin ̽��ֱ��, Astex Pharmaceuticals, Cambridge Science Centre, Cambridge Junction, IET, Hills Road 6th Form College, British Science Week, Cambridge ̽��ֱ�� Health Partners, Cambridge Academy for Science and Technology, and Walters Kundert Charitable Trust. Media Partners: BBC Radio Cambridgeshire and Cambridge Independent.

̽��ֱ��2019 Cambridge Science Festival is set to host more than 350 events as it explores a range of issues that affect today’s world, from challenges around climate change policy, improving safety and quality in healthcare, and adolescent mental health, to looking at what the next 25 years holds for us and whether quantum computers can change the world.

We have everything from the science of perfumery and how your mood affects your taste, to a science version of 'Would I Lie to You?'

Dr Lucinda Spokes

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 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.

Yes

‘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.

“ ̽��ֱ��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.

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

“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.”

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.”

Yes

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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Under pressure: the battle to have a baby in Africa

lw355 — Thu, 16 Feb 2017 09:40:43 +0000

As a young doctor in Uganda a few years ago, Dr Annettee Nakimuli was told that nothing could be done about a complication of pregnancy that was putting thousands of pregnant women a year at risk of death.

She remembers the frustration: “I felt like we were accomplices in this war of sorts. People say we do not remember the words of our enemies but the silence of our friends. I did not want to accept that it was beyond hope.”

̽��ֱ��disease is pre-eclampsia, a condition that is thought to be caused by the placenta developing abnormally. Women with pre-eclampsia often experience very high blood pressure, which can be fatal without medical intervention. Although the condition affects women worldwide, in African women it is more common and particularly severe. It also occurs earlier in pregnancy and can recur in subsequent pregnancies.

“What makes pre-eclampsia such a challenge is it has been impossible to predict or prevent,” explains Professor Ashley Moffett, from Cambridge’s Department of Pathology and Centre for Trophoblast Research, who is an expert on the disease.

“It’s been called the ‘silent killer’ because many women cannot feel the danger sign that their blood pressure is rising until it’s too late. Even when it is detected the only course of action is constant monitoring, and ultimately the only cure is delivery – sometimes at too early a stage for the baby to survive,” adds Moffett.

̽��ֱ��silent killer

Nakimuli knows only too well the difficulties that African women face. Today she’s an obstetrician in Mulago Hospital, Kampala, where 33,000 babies are born each year. It has the highest number of live births of any hospital in the world (around 100 per day), and 15% of pregnancies develop life-threatening complications such as pre-eclampsia, haemorrhage, obstructed labour and sepsis. She describes herself and her colleagues as being “on the front line” in the battle against death in pregnancy and childbirth.

“I would often see women who had had four or more Caesarean sections with no living child – they continued exposing themselves to the danger until they had a baby,” says Nakimuli, who is also a lecturer at Makerere ̽��ֱ��. “I felt like not sitting back and just saying this is a disease with theories.”

Seven years ago, she began work with Moffett through the Cambridge-Africa Programme, first as a MUII PhD fellow registered at Makerere ̽��ֱ��, then as a MUII postdoctoral fellow and now as a research collaborator. Based in Kampala throughout, she would periodically travel to Cambridge to learn new techniques, analyse samples and spend time with Moffett trying to unravel why a complex disease is so much worse in Africa.

A few years earlier, Moffett had discovered that, when the placenta is formed, a remarkable ‘boundary-setting’ process occurs between the mother and the fetus deep within the lining of the womb.

“ ̽��ֱ��placenta must invade the mother enough to access nourishment for the growing baby, yet not so much as to penetrate through the uterus,” she explains. “Placentation is a setting up of the territorial boundary between two genetically different individuals – the mother and her baby, who carries genes from the father. It needs to be in exactly the right place for both to survive and thrive.”

Moffett found that maternal immune cells called uterine natural killer cells mediate the compromise between mother and baby. These cells have unique proteins on their surface called killer-cell immunoglobulin receptors (KIRs), which recognise proteins called MHC on the invading fetal cells. Certain combinations of maternal KIR genes and fetal MHC genes are associated with pre-eclampsia, whereas other KIR genes appear to protect against the disease.

But why would women of African descent suffer so much more from pre-eclampsia than other women? “There was an assumption in Africa that there was a socioeconomic reason, like poverty,” says Nakimuli. “I was convinced that there was something biological.”

Nakimuli set about recruiting 750 mothers at Mulago Hospital to what is the largest genetic study of pre-eclampsia conducted in Africa. She collected blood and umbilical cord samples and, in Cambridge, ‘typed’ the DNA to look at all the genetic variation. “It was kind of a high-risk project, but my determination kept my hope alive. I wanted to find big things.”

Her hunch proved right. She found that the KIR genes that protect African women against pre-eclampsia are different from those that protect European women. Moreover, the risky combination of maternal KIR and fetal MHC proteins occurs at a much higher frequency in sub-Saharan Africa than anywhere else in the world.

We think that women of African ancestry may have these risk genes because of certain beneficial selective pressures, otherwise why would genes that kill mothers and babies be so common in the population?
Ashley Moffett

̽��ֱ��findings immediately opened up new avenues of research into the biology of pre-eclampsia. ̽��ֱ��study also has implications for understanding infectious diseases, as Moffett explains: “We think that women of African ancestry may have these risk genes because of certain beneficial selective pressures, otherwise why would genes that kill mothers and babies be so common in the population? People with the gene that causes sickle-cell anaemia are able to fend off malaria – perhaps something similar is happening for KIR genes? And so now we are starting work to see whether the genes are protecting against infections such as measles, HIV and malaria.”

Africa's Voices

While Nakimuli and Moffett continue pinpointing the genetic basis of pre-eclampsia, and hope to bring out the first comprehensive textbook on African obstetrics, they are aware that one of the key issues surrounding pregnancy is that too many African women go to hospital too late, leaving it until their complications are advanced and dangerous.

“There’s a general lack of awareness and understanding,” explains Nakimuli. “There isn’t even an Ugandan word for pre-eclampsia. ̽��ֱ��closest people get to describing the condition is ‘having hypertension which is different from the other hypertension when you’re not pregnant’. It becomes a mouthful.”

Last year she took part in a series of radio programmes in Uganda as ‘Doctor Annettee’, the on-air doctor ready to answer questions from the audience. ̽��ֱ��programmes were part of an innovative Cambridge-led research project, ‘Africa’s Voices’, which uses interactive radio and mobile communications to gather and analyse the views of ordinary citizens.

“Because of the high rates of maternal mortality, a coping mechanism among Ugandan women is to consider pregnancy as being about bravery and fortitude,” says Nakimuli. “This way of coping might however lead to late self-diagnosis of the warning signs.”

“Sociocultural beliefs like coping mechanisms will determine how people behave,” says Dr Sharath Srinivasan, who is Head of Cambridge’s Centre of Governance and Human Rights and leads Africa’s Voices, “and so it’s important to understand a person’s thinking to support better maternal and neonatal health policies.”

However, the challenge has always been how to collect and assess all of the different ‘voices’ from hard-to-reach African communities. Srinivasan and colleagues realised that Africa’s digital revolution – particularly the widespread use of mobile phones and SMS messaging – could provide the answer when combined with the huge popularity of local radio stations and the team’s technical know-how.

̽��ֱ��team developed a format in which a radio presenter would play a real-life testimonial – such as a woman relaying the complications of her pregnancy – and then invite listeners to reply to a related question by sending a text to a toll-free number. Each respondent would subsequently receive an SMS sociodemographic survey to complete.

“What makes this set-up so rich is the fact that ordinary citizens are encouraged to voice their views. They aren’t restricted by a poll-style yes/no answer,” says Srinivasan. “We’ve developed a methodology that can take this data, which is often complex, unstructured and in more than one local language, and analyse it with qualitative social science and computational techniques to draw out key themes and insights.”

During Africa’s Voices pilot phase, the team used this format in eight sub-Saharan countries, working with nine radio stations, and choosing radio presenters who have a good relationship with their audience. In these ‘social spaces’, they probed beliefs on HIV/AIDS, vaccination, women’s issues, agriculture and governance processes.

Now spun-out of the ̽��ֱ�� as a non-profit organisation, Africa’s Voices works in East Africa with NGOs, health agencies and media organisations, and maintains strong links with researchers such as Nakimuli and Moffett.

An interactive radio project to shed light on pregnancy complications like pre-eclampsia was recently completed with three local language radio stations in Kampala, Uganda, and rich insights emerged into the perceived causes of complications in pregnancy. One finding is the difference in beliefs between men and women.

“Men, more than women, tend to think that the causes of complications are related to enduring traits of the mothers – their biology or their personality – but that the risk of complications is more likely to happen to other women, not their own partner,” explains Srinivasan.

“Women on the other hand are more likely to believe that complications arise because of factors that they can control – such as their lifestyle. Both women and men agree that insufficient health provision is the major reason women delay seeking healthcare.”

Srinivasan suggests from his experience that governments and service deliverers are keen to listen intelligently to what people are saying and to organise their work more attentively to the world views and collective beliefs of the populations they serve. “Sociocultural beliefs that limit the seeking of healthcare are addressable,” he says. “Interventions that engage women and communities in conversations can help change beliefs, opinions and norms, and thus behaviour patterns.”

"We needed to study the disease in Africa"

When Nakimuli is asked what her own research findings on the genetics of pre-eclampsia will mean for the mothers she sees every day on the wards at Mulago hospital, she is pragmatic.

“Can it help medically? We are still far from that,” she says. “Yes, theoretically we can predict risk by genotyping pregnant mothers, but we are in a low-resource setting – everything needs to be cost-effective. Really we need to develop a bedside test that doesn’t require costly and time-consuming laboratory analysis. Then we could know which women need to be monitored carefully.”

Sociocultural beliefs that limit the seeking of healthcare are addressable. Interventions that engage women and communities in conversations can help change beliefs, opinions and norms, and thus behaviour patterns

Sharath Srinivasan

In the seven years since Nakimuli first embarked on her studies to understand why so many women die in pregnancy, Cambridge-Africa research partnerships with Mulago Hospital have widened considerably. They now include pharmacist Dr Ronald Kiguba and Professor Sheila Bird OBE (Medical Research Council Biostatistics Unit, Cambridge) investigating how to report medication errors and adverse drug reactions; microbiologist Dr David Kateete and Professor Stephen Bentley (Wellcome Trust Sanger Institute) tracking how infections like MRSA spread through hospitals; and a group of obstetricians and midwives from Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust looking at best practice with their contemporaries in Kampala.

Meanwhile, a typical day at Mulago Hospital will bring around five pre-eclamptic pregnancies and several cases of obstructed labour, preterm birth and stillbirths; and a team of five doctors will be supervising 80–100 deliveries.

Funds are being sought by Cambridge-Africa to help set up an African Centre of Excellence in Pregnancy and Childbirth at Mulago Hospital, in partnership with Makerere ̽��ֱ��’s College of Health Sciences. “We would like to train more specialised staff who in turn will train the next generation, and we want to turn new understanding of pregnancy complications into clinical interventions,” explains Nakimuli.

Looking back to when she decided not to accept that nothing could be done about pre-eclampsia, Nakimuli says: “I was convinced that the reason we didn’t know much about the disease was because we’d been looking in the wrong place. We needed to study the disease in Africa. After all, if you want to study a disease properly, then you should look at the population most affected by it.”

Dr Annettee Nakimuli was funded by the Makerere ̽��ֱ��-Uganda Virus Research Institute Infection and Immunity Research Training Programme (MUII).

Inset images: Top: Dr Annettee Nakimuli; Bottom: radio interview with 'Dr Annettee' at Akaboozi FM in Kampala, Uganda, as part of the Africa's Voices study (credit: Rainbow Wilcox, Africa's Voices).

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

A complication of pregnancy that causes the mother’s blood pressure to rise – often fatally – is more common in women of African descent than any other. Research in Uganda by African and Cambridge researchers is helping to uncover why.

I felt like we were accomplices in this war of sorts. People say we do not remember the words of our enemies but the silence of our friends. I did not want to accept that it was beyond hope

Annettee Nakimuli

DFID

Suffering from pre-eclampsia, this young mother had to undergo a Caesarean to deliver her twin boys, seen here in the arms of her mother (Malawi)

Graduate, get a job … make a difference #6

Cambridge graduates enter a wide range of careers but making a difference tops their career wish lists. Read about Kathryn Savage who now works in Uganda to improve health service delivery and increase utilisation by strengthening the leadership skills of health workers and district health teams. 'Graduate, get a job … make a difference' is a series in which inspiring graduates from the last three years describe Cambridge, their current work and their determination to give back.

̽��ֱ��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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