̽��ֱ�� of Cambridge - Alfonso Martinez Arias

Human embryo-like model created from human stem cells

jg533 — Thu, 11 Jun 2020 08:05:29 +0000

New ‘gastruloid’ model, created from human stem cells, holds huge potential to understand causes of birth defects and improve disease modelling.

Cambridge researchers win European Research Council funding

sc604 — Thu, 28 Mar 2019 11:00:00 +0000

Two hundred and twenty-two senior scientists from across Europe were awarded grants in today’s announcement, representing a total of €540 million in research funding. ̽��ֱ��UK has 47 grantees in this year’s funding round, the most of any ERC participating country.

ERC grants are awarded through open competition to projects headed by starting and established researchers, irrespective of their origins, who are working or moving to work in Europe. ̽��ֱ��sole criterion for selection is scientific excellence.

ERC Advanced Grants are designed to support excellent scientists in any field with a recognised track record of research achievements in the last ten years.

Professor Clare Grey from the Department of Chemistry, and a Fellow of Pembroke College, leads a project focused on the development of longer lasting, higher energy density and cheaper rechargeable batteries, one of society’s major technological challenges. Batteries are currently the limiting components in the shift from gasoline-powered to electric vehicles.

Using a variety of experimental techniques, including dynamic nuclear polarisation NMR spectroscopy, Grey and her team will explore a variety of different battery chemistries, including more traditional lithium-ion and newer solid state and redox-flow batteries, with a particular focus on understanding the interfaces and interphases that form in these systems. ̽��ֱ��interdisciplinary project combines analytical and physical chemistry, materials characterisation, electrochemistry and electronic structures of materials, interfaces and nanoparticles. ̽��ֱ��final result will be a significantly improved understanding of the structures of new types of batteries and how they evolve during the charge-discharge cycle, coupled with strategies for designing improved battery structures.

Professor Cecilia Mascolo from the Department of Computer Science and Technology, and a Fellow of Jesus College, will lead a project focused on the use of mobile devices for medical diagnostics. Mascolo and her team will study how the microphone in mobile and wearable devices may be used to diagnose and monitor various health conditions since sounds from the human body can be indicators of disease or the onsets of disease.

While audio sensing in a mobile context is inexpensive to deploy and can reach people who may not have access to or be able to afford other diagnostic tests, it does come with challenges which threaten its use in clinical context: namely its power-hungry nature and the sensitivity of the data it collects. Mascolo’s ERC funding will support the development of a systematic framework to link sounds to disease diagnosis while addressing power consumption and privacy concerns by maximising the use of local hardware resources with power optimisation and accuracy.

Professor Christopher Reynolds from the Institute of Astronomy, and a Fellow of Sidney Sussex College, leads a project focused on the feedback from supermassive black holes at the centre of galaxies. These supermassive black holes have a profound influence on the evolution of galaxies and galaxy groups/clusters, but fundamental questions remain.

To help address these questions, Reynolds and his team are studying the highly luminous central regions of galaxies around the black hole, known as active galactic nuclei (AGN). Reynolds’ ERC funding will support a set of projects to explore the multi-scale physics of AGN feedback. A new theoretical understanding of AGN feedback as a function of mass, environment, and cosmic time will be essential for interpreting the torrent of data from current and future observatories, and understanding some of the most powerful phenomena in the universe.

Professor Alfonso Martinez Arias from the Department of Genetics will lead a project focused on understanding the early stages of mammalian embryogenesis. ̽��ֱ��development of an embryo requires the spatially structured emergence of tissues and organs, a process which relies on the early establishment of a coordinate system that acts as a template for the organism. Exactly how this process occurs is an open question and one which is difficult to investigate experimentally, particularly in mammals.

Using gastruloids, a stem cell-based experimental system they have developed, Martinez Arias and his team will probe into the functional relationships between the mechanical activities of multicellular ensembles and the dynamics that control the organisation and shape of the mammalian body plan: the arrangement of tissue and organs with reference to a global coordinate system.

Finally, Professor Austin Smith from the Wellcome - MRC Cambridge Stem Cell Institute and the Department of Biochemistry will lead a project on the plasticity of the pluripotent stem cell network. Pluripotent stem cells have the potential to become any of the cells and tissues in the body, but the evolutionary origins of this phenomenon are unclear.

Using a cross-disciplinary approach, Smith and his team hope to uncover the core biological programme moulded by evolution into different forms. ̽��ֱ��team are investigating the molecular logic governing early development, lineage plasticity, pluripotent identity and stem cell self-renewal.

̽��ֱ��President of the European Research Council (ERC), Professor Jean-Pierre Bourguignon, said: “Since 2007, the European Research Council has attracted and financed some of the most audacious research proposals, and independent evaluations show that this approach has paid off. With this call, another 222 researchers from all over Europe and beyond will pursue their best ideas and are in an excellent position to trigger breakthroughs and major scientific advances.”

Carlos Moedas, European Commissioner for Research, Science and Innovation, said: “ ̽��ֱ��ERC Advanced Grants back outstanding researchers throughout Europe. Their pioneering work has the potential to make a difference in people’s everyday life and deliver solutions to some of our most urgent challenges. ̽��ֱ��ERC gives these bright minds the possibility to follow their most creative ideas and to play a decisive role in the advancement of all domains of knowledge.”

Five researchers at the ̽��ֱ�� of Cambridge have won advanced grants from the European Research Council (ERC), Europe’s premier research funding body.

̽��ֱ��ERC gives these bright minds the possibility to follow their most creative ideas and to play a decisive role in the advancement of all domains of knowledge

Carlos Moedas

̽��ֱ�� of Cambridge

Left to right: Christopher Reynolds, Cecilia Mascolo, Alfonso Martinez Arias

̽��ֱ��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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Scientists develop mouse ‘embryo-like structures’ with organisation along body’s major axes

cjb250 — Wed, 03 Oct 2018 17:00:21 +0000

̽��ֱ��definitive architecture of the mammalian body is established shortly after the embryo implants into the uterus. This body plan has spatial references, or axes, that guide the emergence of tissues and organs: an antero-posterior axis defined by the head at one end and the tail at the other, an orthogonal dorso-ventral axis and a medio-lateral axis, which orientates the arrangement of internal organs like the liver, pancreas or the heart.

Studying the processes orchestrating the formation of early mammalian embryos is hampered by the difficulty in obtaining them. Earlier findings from the Cambridge group had shown that embryonic stem cells could self-organise in culture into structures with an antero-posterior polarity.

Now, in collaboration with researchers from the ̽��ֱ�� of Geneva and the Swiss Federal Institute of Technology Lausanne (EPFL), they have extended the cultures to reveal a capacity of mouse stem cells to produce ‘pseudo-embryos’ that display some of the important characteristics of a normal mouse embryo. Established from only 300 embryonic stem cells, these structures, called ‘gastruloids’, exhibit developmental features and organisation comparable to the posterior part of a six to ten day-old embryo.

̽��ֱ��study shows that gastruloids organise themselves with regard to the three main body axes, as they do in embryos, and follow similar patterns of gene expression. One example of this is the pattern of expression of Hox genes, an ensemble of genes that are expressed in a precise sequential order in the embryo and act as landmarks for different aspects of the body, including the position of different vertebrae or of limbs. This degree of organisation makes gastruloids a remarkable system for the study of the early stages of normal or abnormal embryonic development in mammals.

“These results significantly extend our earlier findings. We were surprised to see how far gastruloids develop, their complex organisation and the presence of early-stage tissues and organ,” says Professor Alfonso Martinez Arias, leader of the ̽��ֱ�� of Cambridge team, at its Department of Genetics.

Professor Denis Duboule from the ̽��ֱ�� of Geneva and at the EPFL explained, “To determine whether gastruloids organise themselves into bona fide embryonic structures, we characterised their level of genetic activity at different stages of development”.

̽��ֱ��researchers identified and quantified the RNA transcribed from gastruloids and compared the expressed genes with those of mouse embryos at comparable stages of development, which showed there was a high degree of similarity.

“Gastruloids form structures similar to the posterior part of the embryo, from the base of the brain to the tail, whose development program is somewhat different from that of the head,” says Dr Leonardo Beccari, co-first author of the study, from the ̽��ֱ�� of Geneva.

These embryo-like structures express genes characteristic of the various types of progenitor cells necessary for the constitution of future tissues.

“ ̽��ֱ��complexity of gene expression profiles increases over time, with the appearance of markers from different embryonic cell lineages, much like the profiles observed in control embryos,” adds Dr Naomi Moris from the Cambridge team, co-first author of the article.

“ ̽��ֱ��implementation of the Hox gene network over time, which mimics that of the embryo, particularly confirms the remarkably high level of self-organisation of gastruloids,” explains Mehmet Girgin, co-first author of the study and PhD student at the Institute of Bioengineering at EPFL.

̽��ֱ��researchers say that these pseudo-embryos will allow an alternative method to animal research, in accordance with the principle of the ‘3Rs’ (the reduction, replacement and refinement of the use of animals in research). ̽��ֱ��finding that so much of the development of an embryo can be recapitulated using stem cells will also increase researchers’ ability to study the genetic mechanisms underlying normal development and disease.

Earlier in the year, the group led by Professor Magdalena Zernicka-Goetz at the Department of Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge reported embryo-like structures capable of generating an anteroposterior axis but which required additional, extra-embryonic, stem cells to generate anteroposterior polarity. ̽��ֱ��new work shows surprisingly that stem cells can self-organise the three axes independently of the extra-embryonic tissues.

“It makes things much simpler for research,” says Professor Martinez Arias. “Not only do gastruloids self-organise to generate the three axes, but they also mimic the spatial and temporal patterns of embryos, without extra-embryonic tissue. This suggests that gastruloids can become a useful tool, particularly in understanding gene expression during development.”

This work was largely funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council.

Adapted from a press release from the ̽��ֱ�� of Geneva.

Reference
Beccari, L, Moris, N, Girgin, M, et al. Multi-axial self-organisation properties of mouse embryonic stem cells into gastruloids. Nature; 3 Oct 2018; DOI: 10.1038/s41586-018-0578-0

Image caption
Seven-day old gastruloid. ̽��ֱ��cell nuclei are marked in blue. Neural progenitor cells (green) are distributed along the antero-posterior axis. Progenitor cells of the tail bud (pink) are confined to the posterior extremity of the gastruloid and indicate the direction of its elongation. © Mehmet Girgin, EPFL

A team of scientists at the ̽��ֱ�� of Cambridge has developed an artificial mouse embryo-like structure capable of forming the three major axes of the body. ̽��ֱ��technique, reported today in the journal Nature, could reduce the use of mammalian embryos in research.

We were surprised to see how far gastruloids develop, their complex organisation and the presence of early-stage tissues and organ

Alfonso Martinez Arias

Mehmet Girgin, EPFL

Seven-day old gastruloid

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̽��ֱ��body in miniature

cjb250 — Tue, 20 Mar 2018 15:22:55 +0000

In Cambridge alone, there are groups growing mini-livers, mini-brains, mini-oesophaguses,mini-bile ducts, mini-lungs, mini-intestines, mini-wombs, mini-pancreases… Almost the whole body in miniature, it seems.

Read more about how these remarkable 'organoids' are helping transform biomedical research - including helping reduce the number of animals used in research.

̽��ֱ��past few years has seen an explosion in the number of studies using organoids – so-called ‘mini organs’. While they can help scientists understand human biology and disease, some in the field have questioned their usefulness. But as the field matures, we could see their increasing use in personalised and regenerative medicine.

David Turner

Confocal microscope image of gastruloid

̽��ֱ��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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