̽��ֱ�� of Cambridge - Kathy Niakan

Cambridge scientists elected as Members of the European Molecular Biology Organisation

jg533 — Tue, 09 Jul 2024 12:00:56 +0000

Five Cambridge researchers join the community of over 2,100 leading life scientists today as the European Molecular Biology Organisation (EMBO) announces its newest Members in its 60th anniversary year.

Pioneering Code of Practice released for use of stem cell-based embryo models in research

jg533 — Thu, 04 Jul 2024 08:17:57 +0000

̽��ֱ�� ̽��ֱ�� of Cambridge, in partnership with the Progress Educational Trust, has led work to create the first ever UK guidelines for the generation and use of stem cell-based embryo models in research.

Project launched to provide guidance on research using human stem cell-based embryo models

cjb250 — Fri, 16 Jun 2023 10:00:58 +0000

̽��ֱ��Governance of Stem Cell-Based Embryo Models (G-SCBEM) project is led by Cambridge Reproduction and brings together scientists, legal scholars and bioethics experts, as well as representatives from major funders and regulators of this research.

Stem cell-based embryo models (SCBEMs) are three-dimensional structures that mimic aspects of embryo development. They can be created from embryonic stem cells, which can be persuaded to form structures that share a number of features with the embryonic blastocyst stage – the stage at which, in conception, the embryo begins the process of implanting into the uterus.

SCBEMs may offer insight into these critical stages of early development – stages that are normally inaccessible to researchers. They also offer potential for understanding some of the problems that can affect early pregnancies and lead to miscarriage or birth defects. Given that one in four pregnancies is estimated to end in miscarriage, this research has the potential to transform treatments for recurrent miscarriage and to improve the success rates of IVF and other fertility treatments.

Research using human embryos in the UK is tightly regulated by the Human Fertilisation and Embryology Act, which prohibits scientists from culturing human embryos in the lab beyond 14 days. However, despite the resemblance to human blastocysts (the cluster of cells that forms about five days after an egg is fertilised), SCBEMS are not themselves embryos. They can be derived from embryonic stem cells but can only form in specific conditions within the laboratory. Because of this, they do not fall under the remit of the HFE Act.

Currently there is no dedicated regulatory framework addressing research using SCBEMs, although existing UK law does prohibit them from ever being transferred into a woman’s womb. Nonetheless, the absence of clear, transparent guidance in this area hinders research and risks damaging public confidence.

Cambridge Reproduction, working in partnership with the Progress Educational Trust (PET), aims to break this deadlock by producing a clear and comprehensive recommended governance framework for research using SCBEMs. As this is an emerging area of research, the team is consulting widely to determine the opportunities, areas of consensus and concerns posed by SCBEMs.

̽��ֱ��consultation will also lay the groundwork for engaging the public and other stakeholders in a parallel two-way dialogue around the use of SCBEMs for research and in translation.

“This is a fast-developing area and the project will open important dialogues with researchers, funders, regulators and the general public,” said Professor Kathy Niakan, Chair of Cambridge Reproduction. “We hope that the resulting self-governance framework will enable scientists to proceed with their research with confidence, while maintaining public trust in this vital area of research.”

“Given the similarities that SCBEMs have with human embryos, they offer enormous potential to unlock secrets of early pregnancy,” said Professor Roger Sturmey from Hull York Medical School, Chair of the G-SCBEM Guidelines Working Group. “However, because of these similarities, it is important that scientists working in this field maintain high standards and public confidence and so we hope that a self-governance framework will provide this.”

Sandy Starr, Deputy Director of PET and a member of the G-SCBEM Oversight Group, said, “SCBEMs open up avenues of research that are vitally important for people affected by infertility or genetic conditions. Use of SCBEMs can advance our understanding of human development, disease and reproduction, improving established reproductive technologies while opening up new possibilities. For this research to thrive, it needs to be conducted responsibly and governed in a clear and transparent way, which is where the G-SCBEM project comes in.”

̽��ֱ��G-SCBEM guidance will be launched in the late autumn, and will be regularly reviewed to ensure that it keeps pace with new scientific developments.

̽��ֱ��G-SCBEM project is funded by grants from the BBSRC Impact Acceleration Account and the ̽��ֱ�� of Cambridge Impact and Knowledge Exchange fund.

̽��ֱ�� ̽��ֱ�� of Cambridge has launched a project to develop the first governance framework for research involving stem cell-based human embryo models in the UK.

We hope that the resulting self-governance framework will enable scientists to proceed with their research with confidence, while maintaining public trust in this vital area of research

Kathy Niakan

Silvia Ferreira (Wellcome Collection)

Human stem cell embedded in a 3D matrix, Cryo SEM

̽��ֱ��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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Researchers call for greater awareness of unintended consequences of CRISPR gene editing

jg533 — Mon, 12 Apr 2021 08:11:52 +0000

CRISPR-Cas9 genome editing is a widely used research tool which allows scientists to remove and replace sections of DNA in cells, allowing them, for example, to study the function of a given gene or to repair mutations. Last year the researchers who developed CRISPR-Cas9 were awarded the Nobel Prize in Chemistry.

In the study published in the journal PNAS, scientists retrospectively analysed data from previous research in which they had studied the role of the OCT4 protein in human embryos during the first few days of development.

̽��ֱ��team found that while the majority of CRISPR-Cas9-induced mutations were small insertions or deletions, in approximately 16% of samples there were large unintended mutations that would have been missed by conventional methods to assess DNA changes.

Research is ongoing to understand the exact nature of the changes at the target sites, but this could include deletions of sections of DNA or more complex genomic rearrangements.

̽��ֱ��discovery highlights the need for researchers who use CRISPR-Cas9-mediated genome editing to edit human cells, whether somatic or germline, to be aware of and test for these potential unintended consequences. This is even more essential if they hope their work will be used clinically, as unintended genetic changes like this could lead to diseases like cancer.

“Other research teams have reported these types of unintended mutations in human stem cells, cancer cells and other cellular contexts, and now we’ve detected them in human embryos,” said Professor Kathy Niakan, group leader of the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute and Professor of Reproductive Physiology at the ̽��ֱ�� of Cambridge, and senior author of the study.

“This work underscores the importance of testing for these unintended mutations to understand exactly what changes have happened in any human cell type.”

̽��ֱ��researchers have developed an open-source computational pipeline to identify whether CRISPR-Cas9 has caused unintended on-target mutations based on different types of next-generation sequencing data.

“We and others are trying to develop and refine the tools to assess these complex mutations, “ added Niakan.

“It is important to understand these events, how they arise and their frequency, so we can appreciate the current limitations of the technology and inform strategies to improve it in the future to minimise these mutations.”

Gregorio Alanis-Lobato, lead author and former postdoctoral training fellow in the Human Embryo and Stem Cell Laboratory at the Crick, said: “Conventional tests used to check the accuracy of CRISPR-Cas9 can miss the types of unintended on-target mutations we identified in this study. There’s still so much for us to learn about the effects of CRISPR-Cas9 technology and while this valuable tool is refined, we need to thoroughly examine all changes.”

There are important ongoing debates around the safety and ethics of using CRISPR-Cas9 genome editing on human embryos for reproductive purposes. And in 2019, there was international condemnation of the work of a researcher in China who edited embryos which led to the birth of twins. In the UK, its use on human embryos is closely regulated and is only allowed for research purposes. Research is restricted to the first 14 days of development and embryos are not allowed to be implanted into a womb.

̽��ֱ��data for this work related to embryos previously studied by the Crick’s Human Embryo and Stem Cell Laboratory. ̽��ֱ��embryos were at the blastocyst stage of early development, consisting of around 200 cells. They had been donated to research by people undergoing in vitro fertilisation (IVF) and were not needed during the course of their treatment.

̽��ֱ��research was led by scientists at the Francis Crick Institute, in collaboration with Professor Dagan Wells at the ̽��ֱ�� of Oxford. Kathy Niakan is Director of the ̽��ֱ�� of Cambridge’s Centre for Trophoblast Research, and Chair of the Cambridge Strategic Research Initiative in Reproduction.

Reference
Alanis-Lobato, G., et al: Frequent loss-of-heterozygosity in CRISPR-Cas9-edited early human embryos. PNAS, April 2021. DOI: 10.1073/pnas.2004832117

Adapted from a press release by the Francis Crick Institute.

CRISPR-Cas9 genome editing can lead to unintended mutations at the targeted section of DNA in early human embryos, researchers have revealed. This highlights the need for further research into the effects of CRISPR-Cas9 genome editing, especially when used to edit human DNA in laboratory research.

We and others are trying to develop and refine the tools to assess these complex mutations.

Kathy Niakan

Arek Socha on Pixabay

DNA

̽��ֱ��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.

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"Reproduction matters to us all": latest issue of Horizons magazine

lw355 — Fri, 20 Nov 2020 11:26:45 +0000

Professor Kathy Niakan talks about why it’s vital to take a multidisciplined approach to understanding the urgent challenges posed by reproduction today – and introduces our Spotlight on some of this work, highlighted in the latest issue of Cambridge's Horizons magazine.

Placenta is initiated first, as cells of a fertilised egg divide and specialise

jg533 — Wed, 23 Sep 2020 15:00:04 +0000

In a study published today in the journal Nature, researchers looked at the biological pathways active in human embryos during their first few days of development to understand how cells acquire different fates and functions within the early embryo.

They observed that shortly after fertilisation as cells start to divide, some cells start to stick together. This triggers a cascade of molecular events that initiate placental development. A subset of cells change shape, or ‘polarise’, and this drives the change into a placental progenitor cell - the precursor to a specialised placenta cell - that can be distinguished by differences in genes and proteins from other cells in the embryo.

“This study highlights the critical importance of the placenta for healthy human development,” said Dr Kathy Niakan, group leader of the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute and Professor of Reproductive Physiology at the ̽��ֱ�� of Cambridge, and senior author of the study.

Niakan added: “If the molecular mechanism we discovered for this first cell decision in humans is not appropriately established, this will have significant negative consequences for the development of the embryo and its ability to successfully implant in the womb.”

̽��ֱ��team also examined the same developmental pathways in mouse and cow embryos. They found that while the mechanisms of later stages of development differ between species, the placental progenitor is still the first cell to differentiate.

“We’ve shown that one of the earliest cell decisions during development is widespread in mammals, and this will help form the basis of future developmental research. Next we must further interrogate these pathways to identify biomarkers and facilitate healthy placental development in people, and also cows or other domestic animals,” said Claudia Gerri, lead author of the study and postdoctoral training fellow in the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute.

During IVF, one of the most significant predictors of an embryo implanting in the womb is the appearance of placental progenitor cells under the microscope. If researchers could identify better markers of placental health or find ways to improve it, this could make a difference for people struggling to conceive.

“Understanding the process of early human development in the womb could provide us with insights that may lead to improvements in IVF success rates in the future. It could also allow us to understand early placental dysfunctions that can pose a risk to human health later in pregnancy,” said Niakan.

̽��ֱ��research was led by scientists at the Francis Crick Institute, in collaboration with colleagues at the Royal Veterinary College, Vrije Universiteit Brussel, Université de Nantes and Bourn Hall Clinic. Kathy Niakan is incoming Director of the ̽��ֱ�� of Cambridge’s Centre for Trophoblast Research, and Chair of the Cambridge Strategic Research Initiative in Reproduction.

̽��ֱ��work was funded by the UK Medical Research Council, Wellcome and Cancer Research UK. It was approved by the UK Human Fertilisation and Embryology Authority (HFEA) and the Health Research Authority’s Research Ethics Committee.

Reference
Gerri, C. et al.: ‘Initiation of a conserved trophectoderm program in human, cow and mouse embryos.’ Nature, Sept 2020. DOI: 10.1038/s41586-020-2759-x.

Adapted from a press release by the Francis Crick Institute.

̽��ֱ��first stages of placental development take place days before the embryo starts to form in human pregnancies. This new finding highlights the importance of healthy placental development in pregnancy, and could lead to future improvements in fertility treatments such as IVF, and a better understanding of placental-related diseases in pregnancy.

Understanding the process of early human development in the womb could provide us with insights that may lead to improvements in IVF success rates in the future.

Kathy Niakan

Fluorescent images showing gene expression in human embryos at early and late stage of pre-implantation development, where blue is each cell of the embryo, green is a cell membrane marker, magenta is a placental gene expression.

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