̽��ֱ�� of Cambridge - Marta Shahbazi

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)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution

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)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes

Licence type:

Attribution

Tempting fate: how to get a head in embryo development

cjb250 — Tue, 13 Oct 2015 10:06:49 +0000

Professor Magdalena Zernicka-Goetz is interested in our fate: not in an existential sense, but rather in the fate of cells at the earliest stages of life. “We look at how cells decide their fate,” she explains. “All of the cells initially look the same, and yet we know that they will go on to make different parts of the body – our hands, our head, the left and right side of our bodies. How do the cells know where to go?”

To read more, including how synchronised swimmers can help us understand embryo development, see the article on Medium.

̽��ֱ��journey from a single fertilised egg cell through to a baby delivered crying into the arms of its mother is one of the most beautiful and complex processes to occur in nature. We are only just beginning to understand the very earliest stages of life – when we are nothing more than a cluster of cells.

Agnieszka Jedrusik and Magdalena Zernicka-Goetz, ̽��ֱ�� of Cambridge

Blastocyst embryo

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

Yes