̽��ֱ�� of Cambridge - European Bioinformatics Institute

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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Cambridge in the 2019 New Year honours list

plc32 — Fri, 28 Dec 2018 22:31:00 +0000

Professor David Klenerman, FRS was knighted for Services to Science and for the Development of High Speed DNA Sequencing Technology.

Professor Klenerman said: “I feel very humbled to be recognised in this way.”

Sir David is a professor of biophysical chemistry at the Department of Chemistry at the ̽��ֱ�� of Cambridge and a Fellow of Christ's College. He is best known for his contribution in the field of next-generation sequencing of DNA, which subsequently resulted in Solexa, a high-speed DNA sequencing company that he co-founded.

“I also want to acknowledge and sincerely thank the highly talented people who have worked with me over the years and without whom my research would simply not have been possible. In particular the development of Solexa sequencing was the result of a massive team effort.”

Klenerman was educated at the ̽��ֱ�� of Cambridge where he was an undergraduate student of Christ's College and received his Bachelor of Arts degree in 1982. He earned his Doctor of Philosophy degree in chemistry in 1986 as a postgraduate student of Churchill College.

Sir David has received a string of honours for his work, including a 2018 Royal Medal from the Royal Society for his outstanding contribution to applied sciences. He was elected as a Fellow of the Academy of Medical Sciences in 2015 and Fellow of the Royal Society in 2012.

Professor Madeleine Julia Atkins, who was first honoured as a CBE in 2011, has been promoted DBE for her Services to Higher Education.

Dame Madeleine, lately Chief Executive of the Higher Education Funding Council for England, has had a long and distinguished career in higher education, most recently providing outstanding leadership in ensuring a smooth transition between HEFCE and the new Office for Students and Research England. She has also been a Trustee and Board member for Nesta, and was until recently a Deputy Lieutenant in the West Midlands. She has been a Pro-Vice-Chancellor at Newcastle ̽��ֱ��, is a former Vice-Chancellor of Coventry ̽��ֱ��, and is now President of Lucy Cavendish College here at Cambridge ̽��ֱ��. She studied for a degree in law and history at Girton College and has a PhD from the ̽��ֱ�� of Nottingham.

Dame Madeleine said: “I am honoured to receive this award, which recognises the contribution of my former colleagues at HEFCE who worked so hard to make the transition to OfS and Research England both smooth and successful. I am delighted now to be bringing some of my experience in the higher education sector to support the students and Fellowship of Lucy Cavendish College”.

Professor John Frederick William Birney, FRS, the joint director, European Bioinformatics Institute was awarded a CBE For Services to Computational Genomics and to Leadership across the Life Sciences.

Professor Birney is Director of EMBL-EBI, Europe's flagship laboratory for the life sciences, and runs a small research group. He played a vital role in annotating the genome sequences of human, mouse, chicken and several other organisms. He led the analysis group for the ENCODE project, which is defining functional elements in the human genome. Birney’s main areas of research include functional genomics, assembly algorithms, statistical methods to analyse genomic information (in particular information associated with individual differences) and compression of sequence information.

Professor Birney, known as Ewan to his friends, family and colleagues, was educated at Eton, Oxford and St John’s College, Cambridge.

Dr Jennifer Mary Schooling, Director of the Centre for Smart Infrastructure and Construction (CSIC), ̽��ֱ�� of Cambridge was awarded an OBE For Services to Engineering and to Digital Construction.

Dr Schooling is a Fellow of Darwin College and has been the Director of CSIC since April 2013. CSIC focuses on how better data and information from a wide range of sensing systems can be used to improve our understanding of our infrastructure, leading to better design, construction and management practices. CSIC has strong collaborations with industry, developing and demonstrating innovations on real construction and infrastructure projects, and developing standards and guidance to enable implementation. Dr Schooling is also Chair of the Research Strategy Steering Group for the newly formed Centre for Digital Built Britain. Dr Schooling is founding Co-Editor-in-Chief of the Smart Infrastructure and Construction Proceedings journal (ICE). She recently served as a member of PAS185 smart cities security standard steering group and of ICE’s State of the Nation 2017 ‘Digital Transformation’ Steering Group. Prior to joining CSIC, Dr Schooling worked for Arup, leading the firm’s Research Business, and before that for Edwards Vacuum (then BOC Edwards) as a manager for New Product Introductions. She has a PhD from the ̽��ֱ�� of Cambridge.

Andrew Nairne, Director of Kettle’s Yard, was awarded an OBE for Services to Museums and the Arts. Kettle’s Yard is the ̽��ֱ�� of Cambridge’s modern and contemporary art gallery.

Andrew Nairne said: “I am delighted to receive this recognition following the hugely successful reopening of Kettle’s Yard in 2018: a magnificent team effort.”

“As Director of one of the eight ̽��ֱ�� of Cambridge Museums, I believe museums have a vital role to play in the life of both the ̽��ֱ�� and the community.”

̽��ֱ��Honours list, which dates back to around 1890, recognises notable services and contributions to Britain.

Members of collegiate Cambridge recognised for outstanding contributions to society in science, education, engineering and art

“I feel very humbled to be recognised in this way.”

Professor Sir David Klenerman

̽��ֱ��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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Celebrating Cambridge’s LGBT+ scientists and engineers

cjb250 — Wed, 04 Jul 2018 23:00:09 +0000

To mark the event, the ̽��ֱ�� has released a film in which staff and researchers from the ̽��ֱ��, AstraZeneca and the Wellcome Genome Campus discuss their experiences of being LGBT+ in Cambridge – and why it is important to be who you are.

"While we have witnessed an increase in inclusion and equality efforts in STEM organisations and companies, we have to recognise the many challenges individuals continue to face, especially members of the LGBT+ community," said Dr Alfredo Carpineti, founder of Pride in STEM and one of the organisers of the initiative. “That's why we launched LGBTSTEM Day. We hope for this to be a day of celebration, of reflection, and of engagement. LGBTSTEM Day is part of the global push to increase the visibility of minorities in STEM fields.”

̽��ֱ��celebrations highlight the need for more role models to help enable LGBT+ scientists and engineers to be able to express themselves and to encourage others to consider a career in STEM. As Dr Sara El-Gebali, Scientific Database Curator at the European Bioinformatics Institute (EMBL-EBI) says in the film: “Sadly there are very few [LGBT role models in science]. It’s not because we’re not here, it’s because we’re not seen. We’re not officially here.”

Anna Langley, Computer Officer at Cambridge’s ̽��ֱ�� Information Services, was one of the founding members of the ̽��ֱ�� of Cambridge’s LGBT+ Staff Network. She works in an environment where diversity is a problem, but says that things that are changing.

“Working in IT is still a very straight, white, male, cis environment,” she says. “But generally, I think that the university is trying to do the right thing in terms of diversity. It’s trying to ensure that people are treated fairly regardless of their background, their gender identity, their sexuality.”

Having a supportive work environment is essential in helping staff both personally and professionally, says Christopher Fox, Associate Scientist at AstraZeneca/MedImmune: “I don’t think I’d be as confident as I am at work if I didn’t have people around me who were openly gay or openly lesbian, people who are happy to be themselves. It made me feel that I can be myself.”

Elizabeth Wynn, Advanced Research Assistant at the Wellcome Sanger Institute, adds: “I think it’s important to be who you are, to be able to live as your authentic self, because you’re never going to be truly happy or productive or complete if you’re trying to silence or hide some part of yourself.”

For Langley, being ‘out’ at work is important not just for oneself, but to support others. “If you’re not visible as someone who’s LGB or T, intersexual, queer, non-binary, whatever, then you’re making it that little bit harder for other people to be open about their experience too, […] to be comfortable in their skin in the working environment.”

̽��ֱ��film’s contributors all describe Cambridge as being a very positive, open city in which to live and work.

“There’s a real emphasis on ‘it’s what you can bring to the table in STEM rather than who you are’,” says Fox. “It’s about what you can achieve, not what your sexuality is.”

Michael Rivera, a PhD student in the Department of Biological Anthropology, agrees: “With such a diverse, knowledgeable population in Cambridge, I think it’s very likely that you will find many friends to make here with common interests to you. You will find lots of allies who are open to different backgrounds and different sexualities – and maybe you’ll even find someone very special to spend time with!”

For Dr El-Gebali, her move to Cambridge has made a huge difference to her life. “Being in Cambridge has helped me to come out, not just to my friends and family, but also to work,” she says. “It’s the first time in my long career when I can officially say ‘Yeah, here I am and I’m not the only one’. Cambridge has been really, really good to me.”

This year, staff and students from the ̽��ֱ�� of Cambridge, Cambridge Assessment and Cambridge ̽��ֱ�� Press, marched together as they joined thousands of others in the parade at Pride London on Saturday 7 July. AstraZeneca and scientists from the Wellcome Sanger Institute also marched together as part of the Proud Science Alliance group.

Cambridge celebrated the first ever LGBTSTEM Day on 5 July – recognising all those who work in science, technology, engineering and medicine and who identify as lesbian, gay, bisexual, transgender and other minority gender identities and sexual orientations.

I think that the university is trying to do the right thing in terms of diversity. It’s trying to ensure that people are treated fairly regardless of their background, their gender identity, their sexuality

Anna Langley

Celebrating Cambridge’s LGBT+ scientists and engineers

Yes

Meet the robot avatars helping Cambridge students combine education and motherhood

sjr81 — Thu, 26 Apr 2018 08:55:23 +0000

Neeta Lakhani and another fellow student are NHS professionals, full-time mothers and part-time students who fell pregnant and gave birth to their children while studying for the Genomic Medicine Masters Programme. Cambridge is believed to be the first university to have used the avatars for classroom teaching.

Using the avatars, which were originally designed to help schoolchildren with long-term illnesses continue their studies, both Neeta and her classmate were able to carry on (virtually) attending their classes in a more profound and engaging way than simply viewing a livestream of the lectures they were missing, or using platforms such as Skype.

̽��ֱ��avatars have microphones, speakers and can move their heads to view both teachers, classmates and presentations – enabling the students to listen, ask questions, talk and interact with classmates and supervisors both during lectures and at breaks.

If the babies are crying, then both mothers can mute the microphones at home so as not to disturb the classroom environment. If they wish to ask a question in class, they can activate a flashing light on the avatar to signal their wish to speak.

Neeta, who alongside her daughter Aniya was filmed for Channel Four News, said: “ ̽��ֱ��way we do it is that that we all get up as we normally do and I get Aniya set up and I get the avatar set up on this end and she just goes through the module with me every day. Whenever she needs attention, I’m able to give it to her without disrupting the class by putting the avatar on silent from my end, but still being able to hear. As soon as she’s settled, I’m able to go back to the avatar.

“I’ve actually found that I’ve concentrated more being at home because it gives me the opportunity to be able to do the two things that I needed to do in the environment that I can most easily do it in. Obviously, the alternative would have been to be in Cambridge and her not be there and I think that would have been very distracting.”

Sarah Morgan, Scientific Training Coordinator at the European Bioinformatics Institute (EMBL-EBI), said: “This was a bit of an experiment for us, but I would say it’s a successful one. ̽��ֱ��robot avatars allowed the two students to participate without physically being in the room. Using the avatars allowed the students to continue their training while caring for their new-borns. It’s certainly inspired us to think outside the box in terms of the needs of our students.”

̽��ֱ��Genomics Medicine Masters Programme is a joint Institute of Continuing Education (ICE) and School of Clinical Medicine course for the ̽��ֱ�� of Cambridge, delivered in collaboration with EMBL-EBI, the Wellcome Sanger Institute, and the Wellcome Genome Campus Advanced Courses and Scientific Conferences.

They are 40cm tall, made of white plastic, and don’t look like your average students, but robot avatars have taken their place in the classroom at Cambridge ̽��ֱ�� – to help two mothers with new-born babies continue their Masters degrees in Genomic Medicine.

I get the avatar set up and my daughter goes through the module with me every day.

Neeta Lakhani

Meet the robot avatars helping Cambridge students combine education and motherhood

European Bioinformatics Institute

̽��ֱ��two student avatars pictured outside the Wellcome Genome Campus

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Anatomy of a decision: mapping early development

cjb250 — Wed, 06 Jul 2016 17:00:34 +0000

̽��ֱ��point in our development when the whole body plan is set, just before individual organs start to develop, is known as gastrulation. Understanding this point in very early development is vital to understanding how humans and animals develop and how things go wrong. One of the biggest challenges in studying gastrulation is the very small number of cells that make up an embryo at this stage.

“If we want to better understand the natural world around us, one of the fundamental questions is, how do animals develop?” says Professor Bertie Gottgens from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute at the ̽��ֱ�� of Cambridge. “How do you turn from an egg into an animal, with all sorts of tissues? Many of the things that go wrong, like birth defects, are caused by problems in early development. We need to have an atlas of normal development for comparison when things go wrong.”

Today, thanks to advances in single-cell sequencing, the team was able to analyse over 1000 individual cells of gastrulating mouse embryos. ̽��ֱ��result is an atlas of gene expression during very early, healthy mammalian development.

“Single-cell technologies are a major change over what we’ve used before – we can now make direct observations to see what’s going on during the earliest stages of development,” says Dr John Marioni, Research Group Leader at EMBL-EBI, the Wellcome Trust Sanger Institute and the ̽��ֱ�� of Cambridge. “We can look at individual cells and see the whole set of genes that are active at stages of development, which until now have been very difficult to access.

“Once we have that, we can take cells from embryos in which some genetic factors are not working properly at a specific developmental stage, and map them to the healthy atlas to better understand what might be happening.”

To illustrate the usefulness of the atlas, the team studied what happened when a genetic factor essential for the formation of blood cells was removed.

“It wasn’t what we expected at all. We found that cells which in healthy embryos would commit to becoming blood cells would actually become confused in the embryos lacking the key gene, effectively getting stuck,” says Dr Marioni. “What is so exciting about this is that it demonstrates how we can now look at the very small number of cells that are actually making the decision at the precise time point when the decision is being made. It gives us a completely different perspective on development.”

“What is really exciting for me is that we can look at things that we know are important but were never able to see before – perhaps like people felt when they got hold of a microscope for the first time, suddenly seeing worlds they’d never thought of,” says Professor Gottgens. “This is just the beginning of how single cell genomics will transform our understanding of early development.”

̽��ֱ��study was made possible by a Wellcome Trust Strategic Award to study Gastrulation and by the Sanger/EBI Single Cell Genomics Centre.

Reference
Scialdone A, et al. Resolving early mesoderm diversification through single-cell expression profiling. Nature; 6 July 2016; DOI: 10.1038/nature18633

Adapted from a press release from the European Bioinformatics Institute.

In the first genome-scale experiment of its kind, researchers have gained new insights into how a mouse embryo first begins to transform from a ball of unfocussed cells into a small, structured entity. Published in Nature, the single-cell genomics study was led by the European Bioinformatics Institute (EMBL-EBI) and the ̽��ֱ�� of Cambridge.

We can look at individual cells and see the whole set of genes that are active at stages of development, which until now have been very difficult to access

John Marioni

Hector Lazo

abstract blood cells

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̽��ֱ��periodic table of proteins

sc604 — Thu, 10 Dec 2015 19:00:00 +0000

A new ‘periodic table’ of protein complexes, devised by an interdisciplinary team of researchers, provides a unified way to classify and visualise protein complexes, which drive a huge range of biological processes, from DNA replication to catalysing metabolic reactions.

̽��ֱ��table, published in the journal Science, offers a new way of looking at almost all known molecular structures and predicting how new ones could be made, providing a valuable tool for research into evolution and protein engineering.

By using the table, researchers are able predict the likely forms of protein complexes with unknown structure, estimate the feasibility of entirely new structures, and identify possible errors in existing structural databases. It was created by an interdisciplinary team led by researchers at the ̽��ֱ�� of Cambridge and the Wellcome Genome Campus.

Almost every biological process depends on proteins interacting and assembling into complexes in a specific way, and many diseases, such as Alzheimer’s and Parkinson’s, are associated with problems in complex assembly. ̽��ֱ��principles underpinning this organisation are not yet fully understood, but the new periodic table presents a systematic, ordered view on protein assembly, providing a visual tool for understanding biological function.

“We’re bringing a lot of order into the messy world of protein complexes,” said the paper’s lead author Sebastian Ahnert of Cambridge’s Cavendish Laboratory, a physicist who regularly tangles with biological problems. “Proteins can keep combining in these simple ways, adding more and more levels of complexity and resulting in a huge variety of structures. What we’ve made is a classification based on underlying principles that helps people get a handle on the complexity.”

̽��ֱ��exceptions to the rule are interesting in their own right, added Ahnert, and are the subject of continuing studies.

“Evolution has given rise to a huge variety of protein complexes, and it can seem a bit chaotic,” said study co-author Joe Marsh, formerly of the Wellcome Genome Campus and now of the MRC Human Genetics Unit at the ̽��ֱ�� of Edinburgh. “But if you break down the steps proteins take to become complexes, there are some basic rules that can explain almost all of the assemblies people have observed so far.”

Ballroom dancing can be seen as an endless combination of riffs on the waltz, fox trot and cha-cha. Similarly, the ‘dance’ of protein complex assembly can be seen as endless variations on dimerization (one doubles, and becomes two), cyclisation (one forms a ring of three or more) and subunit addition (two different proteins bind to each other). Because these happen in a fairly predictable way, it’s not as hard as you might think to predict how a novel protein would form.

Some protein complexes, called homomers, feature multiple copies of a single protein, while others, called heteromers, are made from several different types of proteins. ̽��ֱ��table shows that there is a very close relationship between the possible structures of heteromers and homomers. In fact, the vast majority of heteromers can be thought of as homomers in which the single protein is replaced by a repeated unit of several proteins. ̽��ֱ��table was constructed using computational analysis of a large database of protein-protein interfaces.

“By analysing the tens of thousands of protein complexes for which three-dimensional structures have already been experimentally determined, we could see repeating patterns in the assembly transitions that occur – and with new data from mass spectrometry we could start to see the bigger picture,” said Walsh.

“ ̽��ֱ��core work for this study is in theoretical physics and computational biology, but it couldn’t have been done without the mass spectrometry work by our colleagues at Oxford ̽��ֱ��,” said Sarah Teichmann, Research Group Leader at the European Bioinformatics Institute (EMBL-EBI) and the Wellcome Trust Sanger Institute. “This is yet another excellent example of how extremely valuable interdisciplinary research can be.”

Reference:
Ahnert SE, et. al. ‘Principles of assembly reveal a periodic table of protein complexes.’ Science (2015). DOI: 10.1126/science.aaa2245

Adapted from an EMBL-EBI press release.

Researchers have devised a periodic table of protein complexes, making it easier to visualise, understand and predict how proteins combine to drive biological processes.

We’re bringing a lot of order into the messy world of protein complexes

Sebastian Ahnert

Spencer Phillips, EMBL-EBI

̽��ֱ��periodic table of proteins

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‘Hairclip’ protein mechanism explained

sc604 — Thu, 18 Dec 2014 20:00:00 +0000

New research has identified a fundamental mechanism for controlling protein function. Published today (18 December) in the journal Science, the discovery has wide-ranging implications for biotechnology and medicine.

̽��ֱ��shape of a protein determines its function, for example whether it is able to interact with another protein or with a drug. But a protein’s shape is not constant – it may change in response to different conditions, or simply as a matter of course. Understanding how this process works is key to figuring out how to manipulate proteins, for example in order to disrupt a disease.

̽��ֱ��researchers looked at a family of bacterial RNA-binding proteins that control a basic process in metabolism: one type of bacteria lives in very high temperatures, while the other likes things colder. ̽��ֱ��goal was to determine how a protein morphs from an active configuration (one that lets it bind to RNA) to an inactive one in two very different environments.

“ ̽��ֱ��process is controlled by mutations, but these mutations aren’t in an obvious place, where the binding happens,” explains Sarah Teichmann, of the European Bioinformatics Institute (EMBL-EBI), who led the research. “They’re actually working from a distance, indirectly, to change the shape of those sites. We wanted to know how that works at an atomic level.”

“Any stable protein will have a lot of constraints on its mutational pathways,” said Tina Perica of EMBL-EBI, the paper’s lead author. “These mutations have very few options – just like a person walking along a cliff will need to keep to a narrow path. But at the same time, proteins need enough wiggle room to be able to bind to things, like another protein or a drug. To find where the protein could provide that wiggle room, we retraced its steps millions of years into the past, and used a lot of different approaches to figure out what was happening.”

̽��ֱ��work was a collaboration between Professor Jane Clarke’s biophysics lab in Cambridge’s Department of Chemistry, and Teichmann’s structure genomics protein evaluation lab. “ ̽��ֱ��power of such multi-disciplinary studies is that we can begin to answer questions that neither of us could do alone,” said Clarke.

“If you know how a species of bacteria has evolved, you can reconstruct proteins that it may have had in the past, but which don’t exist today,” says Yasushi Kondo from MRC Laboratory of Molecular Biology. “We made a couple of these proteins, and used X-ray crystallography to solve their structures. That let us see details we would never have seen if we’d only studied proteins from the bacteria that live today. When we put that new information together with computational work and simulations, we started to see a clear picture of how these proteins change.”

“These proteins provide a very good example of a fundamental biophysical phenomenon that we think can happen in many proteins, regardless of which organism,” said Teichmann. “We believe our findings will help future research into manipulating proteins, which has potential applications across the life sciences.”

Adapted from EMBL-EBI press release.

New study describes a fundamental mechanism regulating a protein’s shape and function, with potential applications in biotechnology and drug development.

̽��ֱ��power of such multi-disciplinary studies is that we can begin to answer questions that neither of us could do alone

Jane Clarke

BASF

Microstructures made from designer proteins

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New database for vital model organism launched

gm349 — Mon, 28 Nov 2011 16:16:10 +0000

A new database promises to be an invaluable resource to scientists who use a unique single-celled fungus to study human diseases.

̽��ֱ��new database for the fission yeast Schizosaccharomyces pombe, called PomBase, was launched today by a consortium of researchers at the ̽��ֱ�� of Cambridge, the European Bioinformatics Institute (EBI), and ̽��ֱ�� College London (UCL).

Fission yeast is a single-celled fungus (yeast). Because their cells function much like our own, and it is an important model for studying cellular processes frequently associated with heritable diseases and cancers.

Scientists have already discovered that fission yeast has equivalents of many human genes which are known causes of rare genetic diseases and syndromes (including Batten', Bloom's, Birt-Hogg-Dube, Liddle, Lowe, Niemann-Pick). Additionally, fission yeast have counterparts of human genes implicated in diseases with multiple causes, to include many cancers, deafness, neurological diseases, heart disease, Parkinson's, and anaemia.

Biologists today are very dependent on computer databases that catalogue the functions of the genes of the organisms they study and give access to other supporting information. ̽��ֱ��PomBase website will therefore prove to be an important tool for researchers studying fission yeast.

Its launch is the first stage of a 5-year project funded by the Wellcome Trust to provide a model organism database that allows researchers around the world to participate directly in the curation process in addition to using automated procedures based on the genetic blueprint of the fission yeast. ̽��ֱ��project uses Ensembl software for genome browsing, which is already used to present data for many other important experimental species. Novel tools and resources generated by this project will also be available to researchers working on other species, including human pathogens, to create similar databases.

Steve Oliver, Professor of Systems Biology & Biochemistry, who is spearheading the initiative, commented: "Organism specific database projects frequently have limited resources, and large backlogs of uncurated literature. An important novel component of this project is the construction of intuitive tools to allow the research community to involve itself in database curation, and ensure that the scientific information published in their papers is visible to the entire biological research community. These tools can also be shared with other groups and implemented for their organism of interest.”

Valerie Wood, PomBase Manager and co-investigator, said: "PomBase is not only establishing a database for this important model, it is also adapting the EBI's Ensembl Genomes platform and constructing tools to allow the research community to curate their own publications. ̽��ֱ��PomBase protocols will enable other research communities to establish and sustain similar databases for other experimental organisms. We have already identified counterparts for over 300 human disease genes in PomBase and many of these are being studied to elucidate the cellular basis of a diverse range of diseases.”

Jurg Bahler, fission yeast researcher and PomBase co-investigator from UCL, added: “Many basic cellular processes are conserved between yeast and humans, and PomBase will used extensively by biological and biomedical researchers world-wide to study mechanisms involved in cell growth and division.”

Paul Kersey, PomBase co-investigator from EBI, said: “PomBase has adapted the EBI's Ensembl platform to provide a multi-faceted resource dedicated to the needs of fission yeast researchers. These developments will enable other research communities to establish and sustain similar databases for their favourite experimental organisms.”

̽��ֱ��community curation initiative for PomBase will be launched in Spring 2012. ̽��ֱ��database can be found at: www.pombase.org

̽��ֱ��database, PomBase, important new tool for scientists researching fission yeast.

An important novel component of this project is the construction of intuitive tools to allow the research community to involve itself in database curation, and ensure that the scientific information published in their papers is visible to the entire biological research community.

Steve Oliver, Professor of Systems Biology & Biochemistry, who is spearheading the initiative

Image UCL

Pombe

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