Maintaining genome integrity of adult stem cells is important to prevent cancer initiation and stem cell functional decline during aging. Our recent work (Siudeja, Cell Stem Cell, 2015) has demonstrated that a surprising level of genome instability arises during aging in adult intestinal stem cells of Drosophila. Mechanistically, this is caused by frequent loss of heterozygosity due to mitotic recombination as well as gene inactivation through deletion and complex chromosome rearrangements leading to tumor suppressor inactivation. This model provides an excellent system in which to address important fundamental questions of how stem cell genomes are maintained. The postdoctoral project will further investigate the causes and consequences of stem cell genome instability using Drosophila genetics and whole-genome sequencing approaches.

We are seeking enthusiastic, collaborative, and highly motivated post-doctoral candidates with good Ph.D. track records. Both biologists and bioinformaticians are welcome to apply. Experience in genetics and/or whole-genome NGS sequencing analysis would be appreciated.

Our team is situated within a new, dynamic, international department with state-of-the-art imaging, sequencing, and proteomics facilities at the Institut Curie in the heart of downtown Paris. To apply, please send your CV, cover letter, and names of two references to allison.bardin@curie.fr.

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The Zika virus is making headlines as a major world health crisis linked to a host of neurological conditions. In the cases of microcephaly and Guillain-Barre, the evidence that Zika Virus is the root of the condition is strong enough to be considered causal. Babies born to infected mothers often have microcephaly, a condition that manifests in smaller than average head size and brain development. According to the most recent estimate, the babies of pregnant women infected in the first trimester have between a 1 and 13 percent risk of microcephaly. Guillain-Barre, a condition that can affect infected individuals themselves, is a disorder where a person’s immune cells attack his or her nerve cells. The list of neurological conditions potentially caused by Zika Virus infection doesn’t stop there: there have been case reports of other brain and spinal cord infections .

A new study examines the Zika infection in the brain on a cellular level. Xuyu Qian and his team at John’s Hopkins University used a 3D model of part of the brain to get a more accurate idea of how and where Zika infection occurs in brain. Their results indicated Zika infects a specific type of brain cell.

Until recently, researchers studied cells in the lab in a flat layer on a dish. However, this method did not provide an accurate representation of the complex 3D systems inside our bodies and the bodies of other organisms. Mini-organs, or organoids in scientific jargon, are 3D models of various organs that have burst onto the research scene in the past several years. To study Zika’s effect on the brain, the researchers made mini-brains, specifically modelling the part of the brain called the ‘forebrain.’ They created this mini-brain using ‘human induced pluripotent stem cells,’ which are cells reversed back into stem cell state from adult cells.

As our brains mature, cells specify from stem cells, with stages in between, to specific types of brain cells. On this route to specification, there is a middle step called ‘neural progenitor cells.’ Qian and his colleagues’ research showed that Zika infects these neural progenitor cells more than other types.

The image above shows a mini-brain that corresponds to the first trimester of human fetal development. The image on the left is the mini-brain not infected with the Zika virus and it shows the normal defined stripes, or layers of cells. On the right it the Zika-infected mini-brain, overall loss of structure, quantified by the researchers as reduced thickness of layers.

Using a 3D as opposed to a 2D model is specifically important for studying Zika in the brain because it allows us to see the effect of the virus on properties such as the formation of layers of cells, as well as the tendency to infect certain types of brain cells.

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Postdoc and PhD positions are currently available in the Gouti Lab at Max Delbrück Centre for Molecular Medicine in the Helmholtz Association (MDC), Berlin.

The Gouti lab uses human and mouse pluripotent stem cells to model embryo development in vitro and unravel the mechanisms that regulate cell fate decisions during neuromuscular system development. During embryonic development spinal cord motor neurons are generated with high precision along the anterior-posterior (AP) axis and establish connections with skeletal muscles to control movement. We seek to understand how these two tissues are generated and interact in space and time during neuromuscular system development. 

We have recently succeeded in generating neuromesodermal progenitors (NMP) cells in vitro from mouse and human pluripotent stem cells that can be further differentiated to spinal cord neurons and/or muscle cells. The in vitro generation of NMP cells opens up new opportunities for the study and treatment of neuromuscular diseases as it gives unprecedented access to the simultaneous development of both neural and mesodermal cell types in the “dish” (Gouti et al, Plos Biology 2014; Gouti et al, Trends Genet, 2015;).

We are looking for  highly motivated, talented Postdoctoral fellows and Ph.D students to contribute to the research area of neuromuscular system development and disease. 
Our lab uses, stem cell modeling in parallel with genetic engineering techniques (Crispr/Cas9), next generation sequencing (single cell RNA-seq, ChiP-seq) and live cell imaging.

The MDC provides a state of the art human iPS cell core facility and the opportunity to work in an interdisciplinary environment of research excellence.

The Gouti Lab is actively involved in iMed, which includes five other Helmholtz centers in the Research Field Health besides the MDC. The program aims to interlink and coordinate the research activities of the centers in the field of personalized medicine and, through collaboration with local clinical partners, to promote the rapid transfer of research results into clinical practice.

For the Ph.D. positions interested applicants are encouraged to apply through the MDC Ph.D. program. The deadline for the current open Ph.D. call is 1st of July.  For more information please visit : Ph.D at MDC

For the Postdoc positions, interested applicants should have previous experience in stem cell biology, muscle biology, developmental biology, live cell imaging and/ or analysis of high-throughput  data. Strong publication record and ability to communicate research findings in English are essential.

To apply for a postdoc position, please send a letter of scientific interest along with your CV, publication list and contact information of 2 -3 referees to Mina Gouti (mina.gouti@mdc-berlin.de.). Closing date : 31st of August

For more information please visit: Gouti Lab, Diseases of the Nervous System, MDC

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This post was originally published as a Newsletter article from ShARM (Shared Ageing Research Models)

Scientists using animals in research have a responsibility to ensure that the studies are appropriately designed, conducted, analysed and reported so that they impartially and robustly answer the question they are intended to, and truly add to the knowledge base. Unfortunately there is a large body of evidence, including from the NC3Rs, to show that many animal studies are flawed and that this has significant implications in terms of reproducibility and the translation of findings into potential clinical benefits.

At the NC3Rs we have developed a new exciting online tool which is designed to tackle the problem – the Experimental Design Assistant (EDA).

The EDA is an online resource to help researchers improve the design and analysis of animal experiments. It complements the ARRIVE guidelines for reporting animal research and was developed in collaboration with an expert working group of in vivo scientists and statisticians from academia and industry, and Certus Technology, a team of software designers specialised in innovative software for the life sciences.

The resource is aimed at scientists who use animals in their research. Benefits include advice and feedback on the experimental plans, along with a range of functionalities providing support with the randomisation and blinding of the experiment, as well as sample size calculation. It equips researchers with practical information and knowledge, allowing them to determine the most efficient design for their experiment and understand the implications of choosing a particular design.

A central feature of the EDA is the use of a formal, diagrammatic notation to describe experimental plans and analyses. This is an approach that has been adopted by many technical disciplines to improve communications. It allows the design of an experiment to be recorded clearly and unambiguously and EDA diagrams help convey experimental plans efficiently.

The EDA is not designed to replace specialist statistical advice. For researchers who have limited access to statistical support, the feedback and advice provided by the system will be particularly pertinent, as it will provide users with information, which is specific to the experiment they are planning. For all scientists involved in the research process, the EDA is also extremely useful as a communication tool, for example, between students and their supervisors, or with colleagues and collaborators. These visual representations are far more explicit than the cursory text description traditionally included in grant applications, ethical review submissions or journal publications. Our goal is to integrate the EDA into the scientific process to facilitate better peer review of experimental plans.

We look forward to hearing what you think about the EDA. The feedback has been fantastic but this is a very new and novel system, which has to evolve according to the needs of the research community. Please contact us at eda@nc3rs.org.uk, your feedback will help us ensure that the system improves and evolves according to your needs.

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We know that cells are the building blocks of our bodies. But they are not like inert wooden blocks. They are complicated tiny machines that communicate with each other to make sure that the many simultaneously occurring processes in our bodies are in order.

Stem cells participate in many of these cellular conversations, and a particularly important dialogue is the one that turns certain stem cells into specific types of cells, while keeping others in stem cell state. Retaining stem cells ensures that our bodies can fix the wear and tear of our organs and tissues in future.

So how exactly do cells talk to each other? They send signals using molecules. Setting up a gradient of a certain molecule is one way cells send signals. With many molecules on the surface of cells in one area, and gradually less molecule across space, cells can receive a range of different messages depending on the density of the molecule.

Researchers from the Hubrecht Institute in Utrecht and UMC Utrecht visualized stem cell signaling in the gut for the first time. Their question was how one of the main growth signals in the gut sets up a gradient.

They used artificially made mini-guts (read more about organoids here: http://www.nature.com/news/the-boom-in-mini-stomachs-brains-breasts-kidneys-and-more-1.18064) to study this process.

The image above shows a part of this mini-gut called the crypt, which are the protrusions that give our guts high surface area to allow absorption of nutrients. In panel A, the protrusions are allowed to grow normally. In panels B, C and D, the signal that allows the cells to divide and form the gradient is blocked. Since the signal can’t spread the protrusion can’t grow.

Learning how stem cells signal is important for developing methods to help our bodies regenerate, and to stop this process when it goes awry in the formation of tumours.

Further reading:

http://www.hubrecht.eu/tissue-regeneration-in-the-gut-visible-for-first-time/

Credit

Farin, H. F., Jordens, I., Mosa, M. H., Basak, O., Korving, J., Tauriello, D. V., … & Clevers, H. (2016). Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature.

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One Postdoctoral position is available at the Institute of Biotechnology, University of Helsinki, Finland, in the laboratory of Dr. Nicolas Di-Poi. Our laboratory (http://www.biocenter.helsinki.fi/bi/di-poi/) is studying the development, evolution and regeneration of craniofacial and neural tissues in non-mammalian model organisms that reliably inform human diseases. This is a new and exciting research field, with the goal to provide an evolutionary context to the key signaling pathways of biological regeneration.

The research projects include complementary state-of-the-art methods, including cellular biology, molecular embryology, developmental genetics and phylogenomics, and they offer an interdisciplinary environment for research training (see e.g., Science 339:78-81 (2013), EvoDevo 4:19 (2013), Nature 464:99-103 (2010)). The exact topic of research projects will be discussed in detail during interview.

The successful candidate will have an excellent PhD Degree in Biology and a proven record of excellence in Neuroscience and/or Evo-Devo research. In addition, the Postdoctoral candidate will have a genuine interest in multidisciplinary research and a previous experience of work with central nervous system, brain disease models and/or non-mammalian vertebrate models.

The Institute of Biotechnology (BI) at the University of Helsinki (ranked in the world’s top 100 Universities) is an independent research institute with a mission to increase knowledge in biotechnology and multidisciplinary bioscience and use this for the benefit of society. BI has research programs in Molecular Cell Biology, Developmental Biology, Genome Biology, and Structural Biology & Biophysics. BI offers state-of-the-art facilities in imaging, model organisms, proteomics, genomics, bioinformatics and crystallography. For more information, visit the website: http://www.biocenter.helsinki.fi/bi/.

To apply, please send (in a single pdf document) a cover letter describing your previous research and motivation, your detailed CV including a list of publications, as well as contact information for at least 2 references (including PhD supervisor) to Dr Nicolas Di-Poi (nicolas.di-poi@helsinki.fi). The salary is defined in accordance with the University salary system for teaching and research personnel. The position could start as early as September 2016 or as agreed with the selected candidate. The deadline for the applications is July 31, 2016, but candidates will be considered until the position is filled.

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Post Doctoral Fellowship(s)

‘Deciphering the link between adhesion and pluripotency,”

University of Copenhagen, Denmark

The Danish Stem Cell Center (http://danstem.ku.dk/) is seeking one or two postdoctoral fellow(s) to join the Brickman Lab/DanStem & Michael Lund Nielsen Lab/Centre for Protein Research (CPR)

The post-doctoral positions will initially be supported by a grant from the Lundbeck Foundation and seek to probe the link between pluripotency and cell-cell adhesion. They will follow up recent observations on that focus the gene regulatory network (GRN) sustaining pluripotency on adhesion. The first project, based in the Brickman lab, will follow up the means by which the GRN regulates adhesion and the second, in the Nielsen lab, will focus on deciphering the nature of the adherns junction complex in pluripotent vs differentiating cells

Project description

Embryonic Stem Cells (ESCs) are genetically normal, immortal cell lines with the capacity to become any cell type in the future organism. This project will explore the role of cell-cell adhesion supporting a pluripotent state, both in vivo and in vitro. We recently found that the evolutionarily conserved gene rergulatory network (GRN) downstream of one of the central pluripotency regulators, Oct4, was primarily concerned with regulating cell-cell adhesion (Livigni et al Curr Biol. 2013). Moreover, we found that force expression of E-cadherin could partially block differentiation in response to reduced Oct4 levels in both ESCs and embryos.  These projecst will follow up these observations on at a transcriptional and post-transcriptional level, using a combination of genetic models and mass spectrophotometry.

Qualifications

• Candidates should have experience in embryonic stem cells, developmental biology (mouse and Xenopus) or mass spectrophotometry
• Must be eligible for and prepared to write fellowship applications with in 12 months of being in the laboratory
• Experience with bio-informatics would be considered an advantage

Terms of salary, work, and employment

The employment is for 3 years and is scheduled to start October 1^st or upon agreement. Place of work: DanStem and CPR, University of Copenhagen, Blegdamsvej 3B, Copenhagen. Terms of employment are in accordance with the collective agreement between the Danish Government and the Danish Confederation of Professional Associations

Questions Contact professor Joshua Brickman; Joshua.brickman@sund.ku.dk

Application must include:

• Motivation letter

• Curriculum vitae incl. education, experience, previous employments, language skills and other relevant skills

• Copy of diplomas/degree certificate(s)

• Other information for consideration, e.g. list of publications (if any), letters of recommendationThe University of Copenhagen welcomes applications from all qualified candidates regardless of personal backgroundHow to apply:

• The application, in English, must be submitted electronically. Go to: http://danstem.ku.dk/join/jobs/

The application will be assessed according to the Ministerial Order no. 284 of 25 April 2008 on the Appointment of Academic Staff at Universities

Application deadline: July 10^th 2016

Only applications received in time and consisting of the above listed documents will be considered

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Research assistant position for subsequent appointment as PhD fellow

to the project Deciphering the link between adhesion and pluripotency

The Danish Stem Cell Center (http://danstem.ku.dk) at Faculty of Health & Medical Sciences, University of Copenhagen seeks a Research assistant subsequent appointed as PhD fellow

Job description

Embryonic Stem Cells (ESCs) are genetically normal, immortal cell lines with the capacity to become any cell type in the future organism. This project will explore the role of cell-cell adhesion supporting a pluripotent state, both in vivo and in vitro. We recently found that the evolutionarily conserved gene regulatory network (GRN) downstream of one of the central pluripotency regulators, Oct4, was primarily concerned with regulating cell-cell adhesion (Livigni et al Curr Biol. 2013). Moreover, we found that forced expression of E-cadherin could partially block differentiation in response to reduced Oct4 levels in both ESCs and embryos. This project will follow up these observations. We seek to understand how Oct4 regulates cell-cell adhesion, both at a transcriptional and post-transcriptional level. The project will explore how Oct4 regulates E-cadherin dynamics and how Oct4 targets regulate signaling.

Qualifications

• Master’s degree in biology, biochemistry, medicine or human biology, or similar, and a general understanding of developmental and/or stem cell biology
• Strong motivation and very good scientific skills are essential
• Publications and practical experience are an advantage
• Good communication skills oral and written

Terms of salary, work, and employment

The position as research assistant is for 1 year and as PhD fellow for 3 years. Start October 1^st 2016 or upon agreement.

The employment as a PhD student is conditioned upon a positive assessment of the candidate´s research performance and enrolment in the Graduate School at the Faculty of Health and Medical Sciences. The PhD study must be completed in accordance with the ministerial orders from the Ministry of Education on the PhD degree and the University´s rules on achieving the degree.

Work place: DanStem, University of Copenhagen, Blegdamsvej 3B, Copenhagen. Terms of employment accord to the agreement between the Ministry of Finance and The Danish Confederation of Professional Associations on Academics in the State

Questions Contact Professor Joshua Brickman joshua.brickman@sund.ku.dk.

The application must include

• Cover Letter, detailing your motivation and background for applying for the specific PhD project
• CV
• Diploma and transcripts of records (BSc and MSc)
• Other information for consideration, e.g. list of publications (if any),
• Full contact details of 1-3 professional referees

The application, in English, must be submitted electronically. Go to: http://danstem.ku.dk/join/jobs/

The application will be assessed according to the Ministerial Order no. 284 of 25 April 2008 on the Appointment of Academic Staff at Universities

The University of Copenhagen welcomes applications from all qualified candidates regardless of personal background

Application deadline: July 10^th 2016

Only applications received in time and consisting of the above listed documents will be considered

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Emergence of functional polarity in a tubular epithelium

Applications are invited for a PhD project in the laboratory of Dr. Barry Denholm in the School of Biomedical Sciences at Edinburgh University, UK.

This exciting scholarship scheme provides a unique framework for postgraduate research students to undertake research training and development, together with experience of teaching and mentoring in an international context. Each scholarship covers the UK/EU rate of tuition fee as well as a stipend of £14,296 per annum. Subject to satisfactory progress, the scholarships are awarded for 4 years.

For more information: http://www.ed.ac.uk/biomedical-sciences/postgraduate-studying/phd-research/university-of-edinburgh-career-development-phd/emergence-of-functional-polarity-in-a-tubular-epit

To apply for the position:

http://www.ed.ac.uk/biomedical-sciences/postgraduate-studying/phd-research/university-of-edinburgh-career-development-phd

For informal enquires please contact: Barry.Denholm@ed.ac.uk

Applications due by Friday 17^th June

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May was most notable for the departure of the Node’s brilliant Community Manager, Cat Vicente. Cat said her goodbyes here, but we’d like to take this opportunity to thank her again for her great work over the last 3 years.

And Cat still found time to keep posting right up to the end – both with the latest in our Forgotten Classics series, and her reflections on the inspiration behind Eric Satie’s piano composition ‘Desiccated Embryos‘.

In Cat’s absence, the community has been fantastic at keeping the Node full of content – we’ve had a particularly busy month on the jobs page, and lots of other really interesting content. Thanks to all of you for posting!

Research

Lei wrote about her recent work on the lineage and connectivity of mouse germ cell cysts – and the similarities and differences with Drosophila  oogenesis.

Elizabeth posted on sex determination in flies, and how this translates into sexual dimorphism in body size and in gut physiology.

Hernan and colleagues recently published a software platform for quantitative analysis of tissue organisation. He told us more about the pipeline and its potential applications.

Meetings

Erin and Matthias were at the Inaugural Sainsbury Lab Symposium on Induced Plant Development. They tell us all about the latest advances in this fascinating field.

The latest Company of Biologists’ Workshop “Metabolism in Development and Disease” brought together a diverse group of researchers, including Carlos and Patricia – who give us their reflections on the meeting.

Development is hosting a meeting this September, focussing on the use of stem cell technologies to understand human development. Find out more here, and register soon to secure your place!

Also on the Node

The recent Kumamoto earthquakes devastated the Institute of Molecular Embryology and Genetics. Find out about their recovery efforts.

Nestor got involved with the recent ‘Science Saturday‘ event with The Rockefeller University’s outreach team.

And the SDB is offering the John Doctor Education Prize for the best video explaining ‘Induction’ to a lay audience. Get your thinking caps on and enter for the chance to win $1000!

We hope you enjoy these and all the other posts featured on the Node in the past month. June sees the arrival of our new Community Manager – find out more in a couple of weeks!

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