Posted by Peter Lawrence, on 14 June 2016
Closing Date: 15 March 2021
We have money from our grant to fund a PhD studentship including fees. But there is only a little time left to apply, so if you are interested in our project please look at this advertisement
http://www.jobs.ac.uk/job/ANW638/phd-studentshp-planar-cell-polarity/
José Casal and Peter Lawrence
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Posted by alebur, on 14 June 2016
Alexa Burger, Mosimann lab, Institute of Molecular Life Sciences, University of Zürich, Switzerland.
When I first heard about the “new” genome editing method in early 2013 called CRISPR-Cas9, I thought: “Never ever again will I work with targeted nucleases!” Now it’s mid-2016, we published our approaches to maximize Cas9 effectiveness in zebrafish with Development (Burger et al. 2016), and I happily changed my take to: “Never ever have I seen a system work better than this!” But in all earnest, it was a long (and sometimes bumpy) journey to establish CRISPR-Cas9 in our zebrafish laboratory with its current efficiency and wide-spread applicability. In this blog post, I want to share with you some of our experiences with this method especially for those who are still struggling with getting CRISPR-Cas9 set up in their lab. I want to encourage you to continue working on it – it will work eventually, and we had encountered every possible and impossible problem along the way!
By now, you must have heard of CRISPR-Cas9 for genome editing. In this system, the endonuclease Cas9 is guided to its target location via a short guide RNA (sgRNA or just gRNA, which is the part modified from the original CRISPR repeats) that binds 20 bp of complementary sequence in the genome with its 5’ end and is bound by Cas9 on its 3’ end. By forming this ribonucleoprotein complex (RNP), Cas9 can efficiently cut DNA at your desired locus in the genome of your preferred model organism.
In Spring 2013, I had just moved with my family to Zurich, Switzerland. I had been a postdoc at Massachusetts General Hospital Cancer Center in Boston; as part of the larger Harvard Medical School, I experienced both myself and through collaborators and friends all the ups and downs of using the more complex zincfinger nucleases and later TALENs in zebrafish (so I hope you will relate to my first reaction when hearing about yet another nuclease-based gene editing toy!). Jonas Zaugg, who performed his master thesis in the Mosimann lab, and myself first started looking into CRISPR-Cas9 in autumn 2013 to generate first mutants. As other approaches published at the time (Chang et al., 2013; Hwang et al., 2013; Jao et al., 2013), we injected in vitro-made, capped Cas9 mRNA together with one of the published gRNAs for the zebrafish gene scl24a5, mutants of which are called “golden” due to their resulting yellow-ish pigmentation (Lamason et al., 2005). To be honest, we initially obtained rather lousy results, struggled with the long Cas9 mRNA and the tiny sgRNAs, and I thought to myself “here we go again…”.
Our genome editing game changed completely once we teamed up with Martin Jinek’s laboratory: Martin had done key work on the Cas9 protein itself during his postdoc in Jennifer Doudna’s laboratory at Berkley (Jinek et al., 2012; Jinek et al., 2013), and he had started his lab on-campus around the same time as our PI Christian Mosimann. The two PIs met at a lunch event, and started chatting about their mutual interest in electric string instruments and science. This led to Martin and his graduate student Carolin Anders dropping by our lab with a liquid nitrogen container containing small tubes of (what we call) crystal-grade Cas9 protein that was either GFP- or mCherry-tagged.
Previous accounts of Cas9 protein use in zebrafish were highly encouraging (Gagnon et al., 2014). Using Carolin and Martin’s input on how they treated Cas9-sgRNA complexes in vitro and for structure analysis, we assembled 850-1000 nanograms per microliter of Cas9 with sgRNA into ready-to-use RNP complexes (mixing and incubating at 37°C for 5min, then kept at room temperature) and injected those into zebrafish embryos. A key ingredient turned out to be sufficient KCl salt to keep Cas9 happy with at least 300mM. As documented in our paper, leaving out this crucial step causes the Cas9 RNPs to clump up quickly in the injection needle, so we highly recommend checking for sufficient salt in your final injection mix! The resulting solubilization is applicable to any Cas9 source and should also work with commercial protein stocks (given it is sufficiently concentrated and has an NLS, which is not always the case…).
The subsequent first experiments were, in retrospect, quite funny. We attempted to mutagenize EGFP, which we have abundantly available in our lab’s many transgenics. After the first EGFP targeting injection into homozygous ubi:EGFP embryos, we didn’t see any fluorescence in the embryos the next day. Thinking we messed up the cross, we repeated the experiment and this time we kept some uninjected controls – these were glowing green as usual the next day, but almost none of the Cas9 RNP-injected embryos showed any fluorescence. That’s when it dawned to us that we had mutated the EGFP ORF with such efficiency that there was no functional EGFP protein whatsoever.
Instantly, we could see the difference in all our other CRISPR-Cas9 targeting using our new tricks. And what a difference that was! From about 5 percent (tops) with Cas9 mRNA to up to 100 percent mutagenesis efficiency with the RNPs. We went on to scrutinize every single step in our sgRNA production, injection protocols, genotyping procedures, etc. Along the way, we made all the mistakes one can make: degraded RNA due to dirty pipettes, wrong storage of Cas9 protein stocks, wrong primer sequences ordered (beware of the reverse-complement!), miscalculated injection mixes…the list goes on. All this was topped in the sheer load of sequences we accumulated of targeted loci that we initially needed to analyze by hand. Another key enemy became the frequent single-nucleotide polymorphisms (SNPs) in the zebrafish genome: single SNPs in a 20bp stretch for sgRNA targeting usually abolishes all detectable mutagenesis in our hands, so we frequently sequence targeted loci before injections.
As a lab, we got together and defined some ground rules for our mutagenesis work. We developed the policy to test every new sgRNA on a denaturing MOPS gel. We asked our bioinformatics collaborators in Mark Robinson’s lab next door to code a simple online interface to calculate injection mixes that Lukas Weber coined CrispantCal, which Raul Catena subsequently also turned into a smart phone app. We developed a cloning- and purification-free sequence verification strategy for routine mutagenesis analysis and collected samples for a massive deep-sequencing verification of 40+ loci.
Most importantly, Helen Lindsay from the Robinson lab developed the R-based software tool CrispRVariants for rapid sequence analysis of mutation events (Lindsay et al., in press; preprint at http://biorxiv.org/content/early/2016/03/10/034140). In simple terms, CrispRVariants uses a smart procedure to align sequence results to the intended target locus and performs a base-by-base comparison to the wildtype reference sequence. Paired with sequence counts, CrispRVariants spits out so-called panel plots that visualize the mutagenesis results with allele details. Continuously refined through our day-to-day experiences, these panel plots became a daily discussion point in the lab as we now had a standardized visualization of mutagenesis events – and we hope the online version CrispRVariantsLite will help also you to easily grasp your mutation spectra!
CrispRVariants-based analysis rapidly corroborated that our new protocols achieved exceedingly high mutagenesis efficiencies, reaching even complete biallelic mutagenesis in individual zebrafish embryos. We also started to see previously described loss-of-function phenotypes in injected F0 embryos: we call such Cas9-based somatic mutants “crispants” in analogy to morpholino-injected embryos referred to as morphants. While we do frequently use crispants to figure out if a candidate gene is interesting enough to follow-up as stable mutant in the course of our lab’s work on mesoderm cell fates, we quickly became cautious about using this approach for actual loss-of-function analysis: sequence analysis revealed that most mutated loci have a high propensity to be repaired in a stereotypic set of alleles, including in-frame alleles or even other still functional alleles possibly involving also clonal selection during development. Such effects paired with still variable mutagenesis efficiency make crispant phenotypes for most genes too variable for reproducible, reliable phenotype studies, but nonetheless allow a first glance at the full-blown loss-of-function phenotype. We are harnessing this effect now for limited candidate gene screens for novel cardiovascular regulators and tumor modifiers, and (if space permits!) we alwaysgenerate stable germline mutants for each gene with interesting phenotypes. So beyond tool development, the focus of our endeavors was to be able to probe for new, exciting biology, and we are all enthusiastically applying our new tools to our individual projects.
But keep in mind: realistically, how often do you really need complete mutagenesis? High mutation load in injected animals can perturb their proper development, and you consequently never get adult founders. More important is that, once the Cas9 RNP mutagenesis is optimized, the injections can be titrated to allow for proper development and subsequent screening of germline transmission.
My favorite part of this journey was the collaborative work with protein biochemists, biostatisticians, and our lab’s creative team of biologists. Several spin-off projects have developed and are ongoing in the lab, and we have instructed several outside collaborators in our techniques with hands-on demos during lab visits. Technically, our protocols should be directly applicable to any model organism that allows for injection-based delivery of Cas9 RNPs. In the end however, all comes down to understanding your genetics: once the mutagenesis works, you need to be fluent in the language of classic genetics and quirks such as maternal contribution, phenotype expressivity vs penetrance, hypomorphs, etc. CRISPR-Cas9 is only the beginning. Happy crispring!
Web Links:
CrispantCal web interface: http://imlspenticton.uzh.ch:3838/CrispantCal/
CrispantCal for iPhone: https://itunes.apple.com/nz/app/crispantcal/id1112401634?mt=8
CrispantCal for Android: https://play.google.com/store/apps/details?id=com.raulcatena.crisprcas9
CrispRVariantsLite: http://imlspenticton.uzh.ch:3838/CrispRVariantsLite/
References:
Burger, A., Lindsay, H., Felker, A., Hess, C., Anders, C., Chiavacci, E., Zaugg, J., Weber, L. M., Catena, R., Jinek, M., et al. (2016). Maximizing mutagenesis with solubilized CRISPR-Cas9 ribonucleoprotein complexes.
Chang, N., Sun, C., Gao, L., Zhu, D., Xu, X., Zhu, X., Xiong, J.-W. W. and Xi, J. J. (2013). Genome editing with RNA-guided Cas9 nuclease in zebrafish embryos. Cell Res 23, 465–472.
Gagnon, J. A., Valen, E., Thyme, S. B., Huang, P., Ahkmetova, L., Pauli, A., Montague, T. G., Zimmerman, S., Richter, C. and Schier, A. F. (2014). Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS One 9, e98186.
Hwang, W. Y., Fu, Y., Reyon, D., Maeder, M. L., Tsai, S. Q., Sander, J. D., Peterson, R. T., Yeh, J. R. and Joung, J. K. (2013). Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol 31, 227–229.
Jao, L.-E., Wente, S. R. and Chen, W. (2013). Efficient multiplex biallelic zebrafish genome editing using a CRISPR nuclease system. Proc. Natl. Acad. Sci. U. S. A. 110, 13904–9.
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A. and Charpentier, E. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science (80-. ). 337, 816–821.
Jinek, M., East, A., Cheng, A., Lin, S., Ma, E. and Doudna, J. (2013). RNA-programmed genome editing in human cells. Elife 2, e00471.
Lamason, R. L., Mohideen, M.-A. P. K., Mest, J. R., Wong, A. C., Norton, H. L., Aros, M. C., Jurynec, M. J., Mao, X., Humphreville, V. R., Humbert, J. E., et al. (2005). SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science 310, 1782–6.
Lindsay, H., Burger, A., Felker, A., Hess, C., Zaugg, J., Chiavacci, E., Anders, C., Jinek, M., Mosimann, C. and Robinson, M. D. (2015). CrispRVariants: precisely charting the mutation spectrum in genome engineering experiments. Cold Spring Harbor Labs Journals. http://biorxiv.org/content/early/2016/03/10/034140
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Posted by Allison Bardin, on 10 June 2016
Closing Date: 15 March 2021
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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Posted by jturan91, on 10 June 2016
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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Posted by Mina Gouti, on 8 June 2016
Closing Date: 15 March 2021
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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Posted by Nathalie Percie du Sert, on 7 June 2016
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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Posted by jturan91, on 7 June 2016
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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Posted by Nicolas Di-Poi, on 3 June 2016
Closing Date: 15 March 2021
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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Posted by Danstemjob, on 2 June 2016
Closing Date: 15 March 2021
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
Terms of salary, work, and employment
The employment is for 3 years and is scheduled to start October 1st 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:
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 10th 2016
Only applications received in time and consisting of the above listed documents will be considered
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Posted by Danstemjob, on 2 June 2016
Closing Date: 15 March 2021
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
Terms of salary, work, and employment
The position as research assistant is for 1 year and as PhD fellow for 3 years. Start October 1st 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
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 10th 2016
Only applications received in time and consisting of the above listed documents will be considered
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