The community site for and by
developmental and stem cell biologists

Postdoctoral Associate, University of Maryland

Posted by , on 18 December 2015

Closing Date: 15 March 2021

A position (#121670) is available for a Postdoctoral Scholar to contribute to our studies in neural crest and placode cells. The postdoc will conduct independent research and assist in the training of students in the laboratory of Dr. Lisa Taneyhill at the University of Maryland. Laboratory skills should include the ability to perform various molecular biology and biochemical assays, such as recombinant DNA/cloning; DNA, RNA, and/or protein blotting; immunohistochemistry; and/or in situ hybridization. Experience with microscopy and spectroscopy, chick embryology (including microdissections and electroporation), and tissue culture is desirable. For more information on the lab, please see http://www.ansc.umd.edu/people/lisa-taneyhill. Qualifications: An advanced degree (Ph.D.) in Developmental, Molecular and/or Cell Biology is required. Degree must be earned no earlier than 2010. Fluency in spoken and written English is required. Compensation: Salaries are highly competitive, negotiable and commensurate with qualifications. Fringe benefits offered. Applications will be accepted until a suitable candidate is identified. If interested, please complete the application process at https://ejobs.umd.edu/postings/search

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

Navigate the archive

Use our Advanced Search tool to search and filter posts by date, category, tags and authors.

Frontiers for Young Minds: A New Resource for Budding Scientists

Posted by , on 17 December 2015

Sara M. Szczepanski1,2, Amanda M. Baker3, Robert T. Knight1,2

1Department of Psychology, 2Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720 USA, 3Frontiers, EPFL, Lausanne, Switzerland

 

About six years ago, Dr. Robert Knight, the founding editor of Frontiers in Human Neuroscience, was attending a meeting regarding the future direction of the review process for a top-tier journal, when he suddenly had the idea of involving kids in the scientific review process. The resulting journal, titled Frontiers for Young Minds, was established by Frontiers in collaboration with Knight in 2013. Frontiers for Young Minds is a non-profit, open-access scientific journal for which young people (8-15 year olds) serve not only as the target audience, but also as critical participants in the review of manuscripts written by established researchers. Scientists either volunteer or are initially invited by an Editorial Board Member or an Editor to write research articles that reframe their own recent discoveries published in peer-reviewed scientific journals, or other core areas within their field, so that their research is put into a broader context to specifically target an 8-15 year old audience. This is meant to give scientists the opportunity to share their work with the younger public, while also ensuring that their research is portrayed as accurately as possible.

Next, a young person or a classroom of individuals may volunteer to serve as a ‘Young Minds Reviewer’ and are then paired with a Science Mentor. Together, Young Minds Reviewers and Science Mentors read and discuss articles chosen by the Associate Editors for review. Anyone between the ages of 8 and 15 is eligible to volunteer as a potential Young Minds Reviewer. Science Mentors include both early career Ph.D. students and post-doctoral fellows, as well as senior scientists and medical doctors, who are willing to serve as a direct connection between a Young Minds Reviewer and the scientific community. A Science Mentor is meant to guide his/her Young Minds Reviewer(s) in providing feedback to the authors of their chosen research article. This is similar to the peer review process that established scientists experience on a routine basis when publishing original research articles. Once the authors revise their article to address the comments and concerns of the Young Minds Reviewer(s) and Science Mentor, their article is ready for publication in Frontiers for Young Minds and our superb illustrator adds a fun and descriptive cartoon to each article (see figure below for an example illustration). The end result is a journal full of freely available scientific articles that are written by leading scientists and shaped for younger audiences by the input of their own peers.

In addition to involving individuals and their Science Mentors, Frontiers for Young Minds is also striving to involve science educators and the students in their classrooms. Science educators provide a crucial role in fostering the scientific interests of students starting at an early age. Frontiers for Young Minds is therefore beginning a program where individual classrooms of students can review a scientific article with the guidance of their teacher and a Science Mentor. For example, a seventh-grade class in Princeton, NJ recently reviewed a paper on the uniqueness of human tool use. One of our current efforts is focused on piloting this program in several inner-city schools in Oakland, California. We aim to involve UC Berkeley Ph.D. and post-doctoral fellows as Science Mentors. Other classroom efforts are planned in Rio de Janeiro and Buenos Aires, again initially targeting schools in less privileged neighborhoods. We hope this burgeoning effort will expose many more young people to cutting-edge scientific findings, to help hone their analytical skills, and to educate them on the scientific process at an earlier age. Our goal is to engage and energize young people, so that they learn science is not only fun, but could also be a viable future career option.

Frontiers for Young Minds aims to include a number of different scientific topics that are of interest to young people. Thus far, these topics include: Understanding Neuroscience, Understanding the Earth and its Resources, and Understanding Astronomy and Space Science. Each section contains articles that focus on subtopics within each of these disciplines. For example, within the Understanding Astronomy and Space Science section, potential article topics based on recent, cutting-edge discoveries may include ‘How our Solar System is Organized’ and ‘How a Black Hole Forms’. In the Understanding Neuroscience section, some interesting previous topics have included ‘How Do We See Color?’, ‘How Our Brains Communicate’, and ‘How Ventriloquism Works’.

We think having a scientific journal focused on content for kids and reviewed by kids is a worthy endeavor for a number of reasons. First, Frontiers for Young Minds enables young audiences to actively engage with the scientific process, connecting them with leaders of the scientific community and challenging them to ask questions and to think critically about scientific problems that at the time may be unsolved. Second, Frontiers for Young Minds is a valuable resource for educating and engaging students in science at an early age. The journal platform enables young people to find out first-hand what it is like to be a scientist. This will hopefully encourage more young people to pursue future careers in science. Finally, Frontiers for Young Minds builds a bridge to more directly connect scientists with the public. All articles are written by the scientists who conducted the initial research, but are written in a format that can be understood by the broadest of audiences. This provides young minds, educators, and the general public with a reliable resource for the latest scientific advances.

Frontiers for Young Minds is and will remain in an open-access format. This means that no one will have to pay for a subscription to access the journal content. Articles are free to anyone with an internet connection. We think this is an important model, since we want young people from all socioeconomic backgrounds to have journal access, not just those whose parents or schools are affluent enough to afford access. This is consistent with the goal of the journal to engage as many young people as possible in the scientific process.

We are implementing plans to expand the number of topics covered within the journal and our current efforts are focused on the addition of Earth and Its Resources, Astronomy and Space Science, and Health as new scientific areas. In the near future we hope to provide a link between each article that appears in Frontiers for Young Minds and the journal article containing the original scientific content from which the Frontiers article is based. This link would assist those who are interested in delving deeper into a particular topic of interest. We also have plans to create Spanish, Chinese, French, and German translations of Frontiers for Young Minds. As mentioned above, one of our key goals is to bring Frontiers for Young Minds into classrooms globally.

If you or someone you know would like to get involved as a Young Minds Reviewer, Science Mentor, Author, or Editor, please see http://kids.frontiersin.org/people for more information.

 

Funding

Frontiers for Young Minds is run with generous support from the Frontiers Research Foundation and the Jacobs Foundation of Zurich.

Frontiers for Young Minds is a non-profit, open-access scientific journal for which young people (8-15 year olds) serve not only as the target audience, but also as critical participants in the review of manuscripts written by established researchers.
Frontiers for Young Minds is a non-profit, open-access scientific journal for which young people (8-15 year olds) serve not only as the target audience, but also as critical participants in the review of manuscripts written by established researchers.

 

 

Outreach logo new squareThis post is part of a series on science outreach. You can read the introduction to the series here and read other posts in this series here.

 

 

 

Thumbs up (3 votes)
Loading...

Tags:
Categories: Outreach

From our sister journals- December 2015

Posted by , on 17 December 2015

Here is some developmental biology-related content from other journals published by The Company of Biologists.

 

CoB_DisModMech_AW_RGB

 

A mouse model for tuberous sclerosis complex

The aTSCuthors present a mouse model for tuberous sclerosis complex in which the gene Tsc1  is ablated from eye-progenitor cells, leading to the classic hallmarks of the disease. This demonstrates a role for Tsc1 in regulating several aspects of the development of the visual-pathway. Read the paper here. [OPEN ACCESS]

 

 

Roles for MAP3K1 in the development and survival of cochlear sensory hair cells

chochlear hairs MAP3K1Two papers show that homozygous mutations of the MAP3K1 serine/threonine kinase lead to early-onset profound hearing loss and degeneration of cochlear outer hair cells in mice, demonstrating the role of MAP3K1 in otic development. MAP3K1 is also revealed as a candidate gene for human sensorineural hearing loss. Read the papers here and here. [OPEN ACCESS]

 

 

Loss of TRPML1 leads to impaired myelination and reduced brain ferric iron

brains!Mucolipidosis type IV causes impaired motor and cognitive development, progressive vision loss and gastric achlorhydria, and is caused by mutations in MCOL1. Grishchuk and colleages report that Mcoln1−/− mice suffer developmental defects in brain myelination as a result of loss and deficient maturation of oligodendrocytes, possibly through impaired iron handling. Read the paper here. [OPEN ACCESS]

 

 

Journal typography

 

Lessons from yeast for regenerative biology

yeast!Dhawan and Laxman examine the key concepts underlying our understanding of stem cell quiescence that can be attributed to studies in yeast, and their implications for regenerative medicine. Read the article here.

 

 

Rop is a regulator of dendrite growth

Embedded ImageKim, Parrish and colleagues show that Rop forms a complex with the exocyst, and that this complex predominates in primary over terminal dendrites. Membrane-associated proteins, on the other hand, preferentially diffuse from primary dendrites into terminal ones, suggesting that diffusion supplies membranous material for terminal dendritic growth. Read the paper here.

 

 

The function of NRG1, ErB2 and ErB3 in human placental development

Embedded ImageErB2 and ErB3 are two receptor tyrosine kinases expressed in the extravillous trophoblast (EVT) lineage in the placenta. Fock and colleagues demonstrate that neuregulin 1 (NRG1) promotes EVT formation and suppresses trophoblast apoptosis through the activation of ErB2 and ErB3. Read the paper here. [OPEN ACCESS]

 

 

Luman is a regulator of osteoclast differentiation

Embedded ImageLuman is an ER transmembrane protein that can undergo proteolysis and whose N-terminal fragment can act as a transcription factor. This study shows that Luman can regulate expression, localisation and stability of DC-STAMP, a downstream effector of RANKL, the protein that initiates osteoclastogenesis; making Luman a regulator of osteoclast differentiation. Read the paper here. [OPEN ACCESS]

 

 

Dsor1/MEK activates Wg/Wnt signalling

Embedded ImageHall and Verheyen show that Dsor1, a Drosophila homolog of MEK that is activated by Ras, promotes transcription of  Wg target genes by interacting with Armadillo and preventing its degradation. Ras-Dsor1 activity seems to be mediated by the insulin-like growth factor receptor. Read the paper here.

 

 
Journal typography

 

Spawning behaviour of the Japanese flying squid

Puneetsquid!a and colleagues investigated the spawning behaviour of the Japanese flying squid, comparing eggs spawned in a tank with a temperature gradient with eggs spawned in a tank without a temperature gradient. Only eggs spawned in the tank with the temperature gradient survived. Paralarvae survived for ten days, allowing observation of advanced stage paralarvae. Read the paper here.

 

 

Thumbs up (No Ratings Yet)
Loading...

Tags: , , , , , , , , ,
Categories: Research

Sainsbury funded PhD studentship available: The evolution of plant body plans

Posted by , on 17 December 2015

Closing Date: 15 March 2021

The conquest of land by plants over 450 million years ago was one of the most significant events in our planet’s history, and was underpinned by a series of key innovations in plant architecture during evolution (1).

Our group aims to identify the developmental and genetic basis of two such innovations, three dimensional shoot growth and branching (2, 3) in a range of model systems representing different stages of plant evolution.

Our recently published work reports mutants with disrupted branching patterns in a moss (3-6) and ongoing work has identified mutations that disrupt 3D growth.

Your project will build on these advances to identify molecular determinants of body plan in early diverging land plant lineages.

For further information please see the Harrison lab web page (http://www.bristol.ac.uk/biology/people/jill-j-harrison/overview.html) or contact Dr Harrison directly to discuss your ideas (jill.harrison@bristol.ac.uk).

After discussion, applicants should be prepared to supply a 2-page research proposal, a CV and an academic transcript including the names of three referees.

The deadline is January 20th 2016.

International students are welcome to apply.

Further information:

Gatsby

Nature jobs

Further Reading:

[1] Pires and Dolan (2012). Morphological evolution in land plants: new designs with old genes. Phil. Trans. R. Soc. 367: 508-518.

[2] Olsen et al 2015 DEK1; missing piece in puzzle of plant development Trends in Plant Science 20: 70-71.

[3] Harrison CJ. 2015. Shooting through time: new insights from transcriptomic data. Trends in Plant Science. DOI:10.1016/j.tplants.2015.06.003.

[4] Coudert YN, Palubicki W, Ljung K, Leyser O, and Harrison CJ. Three ancient hormone pathways regulate shoot branching in a moss. eLife 4 e06808.

[5] Bennett et al. (2014a). Plasma membrane targeted PIN proteins regulate shoot development in a moss. Current Biology 24: 1-10.

[6] Bennett et al. (2014b). Paralogous radiations of PIN proteins with multiple origins of non-canonical PIN structure. Molecular Biology and Evolution (doi:molbev.msu147).

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

The Node’s DevBio Quiz!

Posted by , on 17 December 2015

How well do you know your developmental biology images? Can you tell your frogs from your flies and your limbs from your antennae? Here at the Node we’ve come up with a quiz to find out!

 

It’s very easy: we’ve collected a few images of embryonic structures, and all you have to do is guess what they are. To make it even easier we’ve given you four choices for each image.

 

Have fun and let us know what you think in the comments!

 

 

Thumbs up (4 votes)
Loading...

Tags:
Categories: Images

An interview with Nipam Patel

Posted by , on 16 December 2015

This interview first featured in Development.

 

Nipam Patel is a developmental biologist based at the University of California, Berkeley, USA, where he uses a variety of organisms to study the evolution of developmental systems, from arthropod body plans to butterfly colouration. We asked him about his career and scientific interests, his role as an editor at Development, and his growing butterfly collection.

 

Embedded Image

When did you first become interested in developmental biology?

As a high school student. The high school I went to was a public school in Texas with an amazing faculty. I actually had a course in developmental biology then, mainly vertebrate embryology taught out of an ancient little German textbook. Our teacher, Rayburn Ray, also had us doing lab experiments: he would get us chicken eggs to do embryology with. Between my junior and senior high school years I was in a summer programme at UT Austin and got into a lab that did blood cell development work in chickens, where I got to design my own project. So, in fact, my first two papers were from the work I did on chick development as a high school student. These experiences really got me hooked on developmental biology. Then, when I went to college, I was fortunate enough to go into Malcolm Steinberg’s lab as soon as I started as a freshman. From that point on, I knew I was either going to be a developmental biologist or an immunologist, and in the end developmental biology won.

 

During your PhD you worked on Drosophila, but have since moved on to a variety of other organisms. Why?

I did my PhD with Corey Goodman (Stanford University) at the time when the lab had people working on both grasshoppers and Drosophila. I started off working only on Drosophila, but by the time I left I was one of the few people working on grasshoppers in addition to a lot of other odd creatures. A fortuitous experiment led to my finding that a monoclonal antibody (made in collaboration with Thomas Kornberg’s lab) was cross-reactive to Engrailed in a variety of species. This is what got me really excited about evo devo – I realised that, with reagents like this, many of those experiments in comparative developmental biology that people had been talking about could be done relatively quickly. We still do a little Drosophila work, but it is very much the minority.

 

What are the challenges and benefits of working with non-canonical organisms (and establishing new systems, like you recently did with Parhyale)?

The downside is that you can’t just order antibodies for the protein you want to work on; reagents aren’t easy to come by. On the other hand, everything you do and discover is new, and you are not competing against a dozen other labs doing the exact same experiment. It is a lot of fun, but it is challenging. You need to have a certain mindset to be willing to spend a lot of time developing very basic techniques. But it pays off. After all the work that we and others in the Parhyale community have done, the techniques we can now use in Parhyale are pretty impressive (although it’s obviously still orders of magnitude more work than doing experiments in flies). Also, these days many of the techniques being developed in traditional model systems can be quickly shifted to other species. We specifically pick models that provide both evolutionary insights and have fascinating attributes that make them stand out from standard genetic model systems. There is no perfect system though. For example, Parhyale for us has a lot of wonderful properties, but one downside is that its genome is 10% bigger than the human genome. So it took a while before sequencing costs dropped enough to make it feasible for the community to tackle its genome.

 

What are the scientific questions that interest you at the moment?

We are working in three main areas. One is the evolution of the body plan, currently focusing on the function of Hox genes. Although these genes have been studied for a long time, there are still many open questions in animals outside of Drosophila – and now we can do functional experiments, for example using CRISPR/Cas9. We have been focused on understanding Hox function primarily in Parhyale, but complementing this with studies in other crustaceans and insects to better understand their role in evolution. A few years ago we also made the accidental discovery that Parhyale has the ability to replace the germline in a way that seems very different to most other animals, so this is another area of work in the lab.

Our newest area of work grows out of my butterfly collecting hobby, which started when I was 8 years old. I have always tried to do some butterfly work myself, and some people might be familiar with my work on gynandromorphs. Now, I finally have students in the lab whose projects are to study butterflies. We are really interested in structural colours. Many of the colours that you see in butterflies, like reds, yellows and browns, are generated from pigments. Other colours, especially greens and blues, are often structural, created by nanostructures of the scales. These colours have evolved over and over again, so there are many different solutions that can be found, and there are hundreds of beautiful papers from optical physicists that have worked out the physics of these structures. But, in most cases, when the physicists figure out how a particular case works they move on to try to make a man-made material that has the same properties, rather than work out how the butterfly builds these structures during development. This is a very new area of work in the lab, but it is something that I am personally very excited about.

 

Do you have a personal butterfly collection?

I do! I actually have a sizable butterfly collection. I started when I was young, and during my teenage years I collected throughout the USA, India, Africa and Europe. More recently I have been buying some old collections, so I have quite a sizeable collection of my own. This has actually proved really useful for our own experiments. For example, one of the structural colours we work on is in a group of butterflies called the Achillides swallowtails. There are 25 species, and I have 24 of them in my collection. So, if I want to look at the scales of one of the species I don’t even have to go to a museum. When I travel now, I photograph them instead of collecting, and this has also been a great way to learn more about their life histories.

 

Your research has a strong visual component. How important is aesthetics to your research?

It is very important to me. Our lab has a reputation for generating high-quality images. I have a high standard and I hope that my students and postdocs do too. When people look at our figures I want them to see things clearly, and not have to just take our word for details we claim to show. Often, what we strive for in our images is to have them look as good as the actual preparation, because we take great efforts to make our preparations as high quality as we can. But I think this is one of the beauties of the whole field of developmental biology. It is a visually stunning area to work in, and the images have a lot of impact and carry an incredible amount of information. You can convey what you are working on really simply with a couple of images. I have also always been into nature photography, and the photographic qualities of imaging really drive the aesthetic appeal for me.

 

What are the challenges of quantitative imaging?

One issue is to know what to quantitate. Nowadays you can take many images and extract a lot of numerical information, but I am not always sure it is useful. Another challenge that has become really apparent is how to capture complex spatial information. Quantitating level or timing is relatively easy, but finding automated and quantitative ways to capture patterns, for example, is a lot harder. Take the work I do on gynandromorphs. I can easily look at the wings and immediately tell you where the boundaries are, as I know the butterflies very well, but teaching a computer how to do it is a huge challenge. More and more data are in the form of images on the internet. How to mine those data easily is a different type of quantitative imaging problem.

 

In the last few years funding bodies have put an increased emphasis on translational impact. Do you think the evo devo field has been particularly affected by this?

Partially yes. I think a lot of evo devo people didn’t necessarily get NIH funding anyway, so the move towards translational research most impacted those that did. Traditionally, a lot of evo devo funding has come from the NSF, which is much more open to that kind of work. However, evo devo has been affected by the general tightness of funding. This, in addition to there being an increasing number of people in the field, has made it harder to secure funding.

 

You have been an editor with Development for several years. How has your experience as an editor been?

It has been really fulfilling. First of all it allows me to keep up with the leading edge of the evo devo field, not only through the papers that are submitted but also because, as an editor, people often approach me about whether the work they are doing is appropriate for Development. I have enjoyed trying to help out authors who have interesting stories to tell, and making sure their work gets published. It has also been fun to handle papers from more standard systems, such as Drosophila and sea urchins.

 

Is there any particular type of paper or topics that you would like to see more of in Development?

Development has published many of the very classic evo devo papers since the early days of the field, including some of mine when I was a graduate student. I would like to see us attract those very best evo devo papers in greater numbers, high-quality papers that have compelling stories to tell. The journal has very high standards, so they have to be very high-quality papers. In general, what might have been published 5 or 10 years ago isn’t going to pass the bar nowadays. Increasingly, there is the ability to conduct manipulative experiments in non-canonical systems, so in many cases we would expect it to some degree. There are, of course, exceptions, and a particularly striking descriptive paper may still be appropriate.

There is often this notion that Development is only a journal for mechanistic development, which some people interpret as only molecular mechanism. I want to make it clear that this is not the case. Those papers that have really important implications for evolutionary mechanisms are also very welcome in Development.

 

Do you have any advice for young scientists?

I think it is unfortunate how senior people sometimes start off by talking about how funding is hard. There have always been challenges. I think that if young people are very excited and passionate about what they work on, they should go for it. It is tempting to think ‘I am going to work on this because it is a hot field with a future’. This is very hard to predict, and in 6 or 7 years time it might be completely transformed and not the hot field anymore. I think that if you have a passion for something and you think you can find novel, interesting ways to approach it, that is really what you should do.

 

Thumbs up (5 votes)
Loading...

Tags: , , ,
Categories: Interview

Research Assistant (Karadottir Lab)

Posted by , on 16 December 2015

Closing Date: 15 March 2021

Department/Location: Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, University of Cambridge

Salary: £25,023-£28,982

Reference: PS07891

Closing date: 12 January 2016

Fixed-term: The funds for this post are available for 12 months in the first instance.

The Wellcome Trust – Medical Research Council Stem Cell Institute draws together outstanding researchers from 25 stem cell laboratories in Cambridge to form a world-leading centre for stem cell biology and medicine. Scientists in the Institute collaborate to generate new knowledge and understanding of the biology of stem cells and provide the foundation for new medical treatments.

We are looking for a motivated, and independent research assistant to join a research project to further investigate how neurons and glutamate signalling regulate CNS stems cells differentiation and remyelination in white matter diseases, a mechanism we recently identified as being important for myelin regeneration (Gautier et al, Nature Communications 2015). The project will involve identifying new mechanisms of how neurons regulate CNS differentiation and new drug targets that can be used to augment myelin regeneration.

Homepages of the team: http://www.stemcells.cam.ac.uk/researchers/principal-investigators/dr-ragnhildur-thra-kradttir

Requirements: We are looking for candidates, with a BSc level qualification in the field of neuroscience/biochemistry/stem cell biology/medicine, and that have experience working with animals. Candidates with experience in surgery and/or molecular biology are particularly encouraged to apply.

We are specially looking for candidates that are collaborative with effective communication skills and enjoy working in a team.

Start date is flexible but can be as early as February 2016. This position is available on a full-time or part-time basis.

This project is a collaboration between Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, Department of Chemical Engineering and Biotechnology, the Department of Chemistry, Department of Biochemistry, and the Department of Clinical Neuroscience at the University of Cambridge.

Once an offer of employment has been accepted, the successful candidate will be required to undergo a health assessment and a security check.

To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/9008. This will take you to the role on the University’s Job Opportunities pages. There you will need to click on the ‘Apply online’ button and register an account with the University’s Web Recruitment System (if you have not already) and log in before completing the online application form.

The closing date for all applications is the Tuesday 12 January 2016.

Please upload your Curriculum Vitae (CV) and a covering letter in the Upload section of the online application to supplement your application. If you upload any additional documents which have not been requested, we will not be able to consider these as part of your application.

Informal enquiries about the post are also welcome via email on jobs@stemcells.cam.ac.uk.

Interviews will be held in mid-January 2016. If you have not been invited for interview by 30 January 2016, you have not been successful on this occasion.

Please quote reference PS07891 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

In Development this week (Vol. 142, Issue 24)

Posted by , on 15 December 2015

Here are the highlights from the current issue of Development:

 

New markers for human endoderm differentiation

Embedded Image

The generation of mature cell types from pluripotent stem cells (PSCs) relies on lineage-specific markers to track and enrich for distinct cell populations. During hepatocyte differentiation, the induction of the definitive endoderm is a crucial step; however, to date there are no markers that exclusively recognise differentiating human endoderm, nor any that can select for hepatocyte-fated cells from within this population. Now, on p. 4253, Gordon Keller and colleagues report on the identification of two antibodies that can be used to identify and select for cells undergoing human endoderm differentiation from PSCs. The authors name the antibodies HDE1, which exclusively marks the entire endoderm population as it emerges, and HDE2, which marks emerging hepatic progenitors and mature hepatocytes. The authors show that the extent of HDE1 reactivity correlates with hepatic potential, and, importantly, that the two antibodies work across numerous different human PSC lines. This exciting breakthrough enables the individual monitoring of both endoderm induction and hepatic specification, leading to a more efficient protocol for directed differentiation of human hepatocytes from PSCs.

 

Local mechanism for decline in stem cell proliferation

Embedded Image

As tissues age, the rate at which endogenous stem cells proliferate is known to decline, leading to prolonged periods of quiescence and fewer stem cell progeny. Nutrient status is a key regulator of stem cell proliferation; however, it remains fairly constant across all tissues in the body, whereas rates of stem cell proliferation can vary widely among tissues. In order to explain this phenomenon, there must be a mechanism for the local regulation of stem cell proliferation, but so far this has remained elusive. Now, on p. 4230, Jean-Claude Labbé and colleagues uncover a process that mediates a local decline in germline stem cell (GSC) proliferation in C. elegans. The authors show that an accumulation of differentiated progeny, in this case oocytes, causes a decrease in GSC proliferation rates. Interestingly, this induced GSC quiescence is caused by local inhibition of insulin/IGF-1 signalling mediated by DAF-18/PTEN, but not DAF-16/FOXO, signalling downstream of oocyte accumulation. Since insulin/IGF-1 signalling operates in all animals including humans, these results represent an exciting breakthrough in our understanding of how stem cell proliferation and quiescence can be regulated in a tissue-specific manner, and may have important implications for disease.

Size matters: lessons from the planarian on organ scaling

Embedded Image

Despite many advances in understanding stem cell regulation and growth signalling, the developmental mechanisms controlling organ size attainment remain elusive. How does an organism know when the appropriate number of cells in an organ has been reached, either during development or regeneration? In this issue (p. 4217), Christian Petersen and Eric Hill describe a novel system to investigate whole cell number control during organ regeneration in the planarian. In their study, the authors report how a specific ratio of brain neurons to body size is maintained during periods of organismal growth, shrinking and regeneration. Using this foundation, the authors demonstrate how wnt11-6 (expressed at the posterior of the brain) and the Wnt inhibitor notum (expressed at the anterior of the brain) co-regulate each other and ultimately determine brain size. Further, the authors show this is not through cell proliferation or death, but through a pathway involving canonical and non-canonical Wnt signalling that influences neural progenitor numbers. Taken together, these results illustrate a genetic mechanism for the loss of cell number during regeneration and show how stem cell regulation can be responsible for organ size reduction.

MAP(K)ping out binary fate decisions in ESCs

Embedded Image

One of the earliest events in mammalian development occurs when the inner cell mass segregates into two distinct cell populations: the epiblast (Epi) and the primitive ectoderm (PrE). Much is known regarding the molecular and signalling pathways that regulate this early fate decision, but what remains unclear is how these inputs are integrated into the molecular circuitry in order to regulate precisely the temporal and spatial emergence of these two cell lineages. Now, on p. 4205, Alfonso Martinez Arias and colleagues investigate this question using multicolour single-cell quantitative assays and mathematical modelling, and demonstrate a dual role for FGF/MAPK signalling in the decision between PrE and Epi cell fates. Firstly, the authors show that in order for GATA factors to activate the PrE gene expression programme, the FGF/MAPK pathway must be inhibited. Secondly, the authors demonstrate that MAPK signalling also sets the threshold level of GATA transcription factors required to specify the PrE lineage, and thereby controls the proportion of PrE cells. These data are used to parameterise a binary switch network model that describes the mechanism and predicts how MAPK input is incorporated into the network.

On the origins of organ-specific vessel formation

Embedded Image

Every organ must be properly vascularised in order to receive nutrients and signals, and to remove waste. Although it is clear that some blood vessels show features specific to their organ of origin, it is not yet understood how organ-specific vessels arise during embryonic development, nor what the molecular mechanisms are that regulate their formation. In this issue (p. 4266), Karina Yaniv and colleagues use the zebrafish subintestinal plexus, a vascular bed that gives rise to the vessels of the gut, liver and pancreas, to dissect the early cellular and molecular events of organ-specific vascularisation. The authors show a common origin for all cells within the subintestinal plexus: a pool of specialised angioblasts located in the floor of the posterior cardinal vein. The authors demonstrate that these specialised angioblasts undergo two rounds of migration and differentiation, which are regulated by BMP and VEGF, respectively. Interestingly, Notch is required only during later stages of subintestinal plexus development, and not earlier. These results provide new insights into the origins of organ-specific blood vessels and showcase the zebrafish subintestinal plexus as a powerful model for characterising this phenomenon.

 

PLUS…

 

Tendon development and musculoskeletal assembly: emerging roles for the extracellular matrix

DEV4191Tendons are ECM-rich structures that interconnect muscles and bones. Here, Subramanian and Schilling review how intrinsic mechanisms as well as extrinsic factors, such as mechanical force, regulate the ECM to control tendon development and maturation. See the Review on p. 4191

 

 

Featured movie

 

Our latest feature movie shows ESCs expressing a H2B-Cerulean transgene under the control of the CAGS promoter. Read the paper by Martinez Arias and colleagues, where they use mouse ESC lines to study the mechanism underlying the decision between the Epi and the PrE fate, on p. 4205

Thumbs up (No Ratings Yet)
Loading...

Categories: Research

Postdoc on transgenerational epigenetic inheritance (TEI) in C. elegans

Posted by , on 15 December 2015

Closing Date: 15 March 2021

The lab of Mihail Sarov atThe Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany is offering a 3 year

as part of a HFSP funded project to explore the mechanisms of transgenerational epigenetic inheritance (TEI) in C. elegans.

project summary:

Epigenetics adds a fundamentally important layer of gene expression plasticity that can improve the ability of cells and organisms to adapt to the constant changes in their environment. Importantly, studies in multiple systems have demonstrated that epigenetically encoded states of gene activity can be maintained and transferred across generations. When C. elegans is exposed to exogenous double-stranded RNA (dsRNA) genome loci of cognate sequence are silenced by RNA interference (RNAi). If selective pressure is applied for a few generations the silenced state of targeted genes becomes stable without further selection, a process accompanied by heritable changes in the local chromatin structure. Hence, an animal can acquire stably inheritable phenotypic traits by exposure to RNAi triggers. This research program will probe the extent of TEI impact in animal epigenetic plasticity and environmental response, define its underlying mechanisms, and generate a predictive and quantitative model for RNAi-mediated TEI.

The MPI-CBG provides highly competent and well-organized services and facilities and excellent mentoring and career development opportunities. You will have the freedom to develop your own research direction within the framework of this project.  The project is a close collaboration with 2 other labs – Eric Miska (Cambridge, UK) and Thomas Duchaine (McGill University, Canada) and will provide ample opportunity for exchange of ideas and techniques, including short-term visits to the partner labs.

requirements: 

We are looking for an ambitious and highly motivated scientist with experience in the fields of epigenetics, nuclear organisation, and/or RNA mediated gene silencing mechanisms. Experience with Chromatin IP, ATAC-seq, Single Molecule FISH or single cell genomics methods will be highly beneficial.

To apply please send your CV including the contacts of 3 researchers who can be approached for reference letters and one page motivation letter outlining your prior experience and future plans. Please use our online application system

The position is available immediately. There is no deadline for this application.

We especially encourage women to apply. The Max Planck Society is committed to employ more people with disabilities and actively seek their applications.

The Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, is a highly visible and international research institute focused on cell and developmental biology. Currently about 500 employees are working at the institute, where half are from abroad with 53 nations represented. MPI-CBG has twice been awarded the title “Best Place to Work” (Academia and postdocs) by the journal “The Scientist”. It tops the list of the top ten research institutions outside the United States in 2009, and is the only German institution listed. Further information on the research environment at MPI-CBG Dresden can be found at our website www.mpi-cbg.de.

Max Planck Institute of Molecular Cell Biology and Genetics
Code: 2015-PostDoc-4181
Pfotenhauerstr. 108
01307 Dresden, Germany

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

High-speed imaging of entire organisms at sub-cellular, isotropic resolution

Posted by , on 14 December 2015

A microscope has long remained a biologist’s favorite tool, and for obvious reasons, as it has been the tool to continually grant us deeper access into the elusive world that has always remained close and yet, typically, out of sight. Recent advancements in light sources, detectors, opto-mechanical components, and powerful computing frameworks have collectively accelerated the field of bio-imaging. So, what once was a qualitative and curious glance into the microscopic world beneath us is now a quantitative field of imaging the micro- and the nano- world.

Ventral and lateral views of a gastrulating Drosophila embryo imaged with IsoView.
Ventral and lateral views of a gastrulating Drosophila embryo imaged with IsoView.

More recently, recording live specimens in three-dimension over an extended period of time has been made possible with the application of light-sheet microscopy in imaging fluorescently-tagged biological specimens [1,2]. Despite affording the flexibility to gently assess a live specimen with reduced photobleaching and phototoxicity, a majority of high-end light-sheet microscopes available today still suffer from anisotropy in spatial resolution, in much the same way as a wide-field microscope. The resolution along the direction sampled by the objective for depth-sectioning tends to be much worse than that in the plane viewed by the objective. In other words, the axial (z- or depth) resolution is much worse than the lateral (x- and y-) resolution. This glaring anisotropy in spatial resolution stems from the way an objective collects the emitted photons from a fluorescent object. Although a fluorescent object emits photons in all directions, a detection objective only captures photons that are emitted within a cone of its viewing angle (defined also by a parameter called the numerical aperture or NA). Even high-NA lenses in immersion media fail to capture the entirety of the photons emitted by the sample, and as such, much less information is gathered about the axial content of the object compared to the lateral content. Thus, the anisotropy in the spatial resolution isn’t an artifact of under-sampling in the axial direction, but rather a physical limitation imposed by the very way an objective collects the emitted photons.

In light-sheet microscopy, the anisotropy in spatial resolution can be mitigated by either making the light-sheet quite thin as in a lattice light-sheet microscope [3] or collecting the image data along multiple viewing angles [4,5]. The first approach however limits the overall coverage of the sample we can image and also takes longer to scan across a relatively large sample. In the context of imaging large specimens at a high temporal resolution, this approach thus tends to be limiting. The second approach of acquiring volume stacks from multiple viewing angles does indeed offer a solution to the problem of resolution anisotropy, but the implementation has either been through the rotation of the sample at various angles to acquire multi-view image-stacks [4] or, more recently, via a pair of shared illumination and detection objectives as in the dual-view plane illumination microscope (diSPIM) [5]. Rotating the sample in multiple orientations for the acquisition of multi-view image-stacks penalizes the overall acquisition time, and thus limits imaging to processes that don’t have a stringent temporal sampling requirement. Using a pair of shared illumination and detection objectives to sequentially capture the image-stacks along two orthogonal directions, as in the now commercial diSPIM microscope, offers a user-friendly implementation for use in a laboratory workbench, but this method is limited to small, transparent samples such as C. elegans embryos.

Today, the frontiers of live three-dimensional imaging has also reached the domain of recording neuronal activities across the whole-brain of a live animal [6,7], which places high demands on the spatio-temporal resolution to reliably discern neuronal activities from within an ensemble of densely packed neuronal population. To make accurate predictions of the temporal and spatial dynamics of such processes, there has indeed been an immense need for an imaging tool that not only captures three-dimensional images at an isotropic, sub-cellular resolution, but also does so at a high temporal resolution and over an extended period of time in large and non-transparent animal models such as Drosophila and zebrafish, for which a plethora of genetic tools are already available and are constantly being updated.

The development of isotropic multi-view (IsoView) light-sheet microscopy overcomes the spatio-temporal resolution and physical coverage limitations of earlier approaches and now allows isotropic, sub-cellular resolution imaging of large, non-transparent samples at a high temporal resolution [8]. The IsoView design utilizes an orthogonal arrangement of four shared illumination and detection objectives surrounding a sample. Thus, the axial dimension along two opposing views becomes the lateral dimension along the orthogonal views, and the fusion of the image content from all four views and the subsequent deconvolution of the multi-view images results in a spatially isotropic three-dimensional representation of the sample. Additionally, IsoView enables simultaneous four-view imaging by spatially offsetting the orthogonal light-sheet scans in the vertical direction and equally offsetting the active row of pixels in the orthogonal cameras. As such, although all four light-sheets and all four cameras are operated simultaneously, neither the illumination beams in the orthogonal illumination arms nor the active row of camera pixels in the orthogonal detection arms cross paths with one another. In this manner, the simultaneous acquisition of four views doesn’t sacrifice the volumetric acquisition speed for spatially isotropic imaging and allows one to follow fast, dynamic processes with sub-second temporal resolution. In characterizing the IsoView system performance, we measured the isotropic resolution to be approximately 450 nm using fluorescent beads embedded in agarose. Furthermore, we measured the effective isotropic resolution to be 1-2 microns in vivo by characterizing fluorescent beads injected at various depths in a Drosophila embryo, which better mimics the actual performance in an optically challenging biological environment.

As our first demonstration, we performed IsoView imaging of an entire 1st instar Drosophila larva expressing cytoplasmic GCaMP throughout its nervous system at a rate of 2 volumes/sec over a period of over 8 hours— an illustration of a functional imaging experiment performed at developmental timescales. To the best of our knowledge, this is the first demonstration of whole-animal functional imaging performed in a higher invertebrate. The IsoView images from this recording show cellular and sub-cellular morphologies with unprecedented details along all viewing angles, thus constituting an accurate three-dimensional representation of the sample that no longer suffers from spatial resolution bias along any preferred direction. We also demonstrated isotropic, sub-cellular resolution functional imaging at a sustained rate of 1 volume/sec in a 3-day old zebrafish larva expressing GCaMP throughout its nervous system. To the best of our knowledge, this constitutes a first demonstration of spatially isotropic, sub-cellular functional imaging of a whole-brain in a vertebrate. The images from this recording show the power afforded by IsoView in unambiguously discerning single neurons even from within a dense ensemble of neurons located deep inside a large specimen such as a zebrafish larva, the size of which is approximately 400-fold larger than C. elegans embryos. Lastly, a demonstration of simultaneous two-color imaging was also performed in a gastrulating Drosophila embryo expressing nuclear-localized RFP and membrane-localized GFP. The entire volume of the embryo was acquired from four views in both color channels every 4 seconds, which offers good temporal resolution to capture in detail key events during gastrulation, such as ventral furrow formation, cephalic furrow formation, movement of pole cells, and germ-band extension (Figure). Owing to the isotropic micron-level resolution, we were able to reliably distinguish neighboring cells and resolve morphological features at the subcellular level across the entire embryo in the 2-color recording of the gastrulating Drosophila embryo.

The above discussed demonstrations of 2 Hz whole-animal imaging in a Drosophila embryo (and eventually, larva) for over 8 hours, 1 Hz whole-brain imaging in a 3-day old zebrafish larva, and simultaneous two-color imaging of a gastrulating Drosophila embryo show the breadth of imaging IsoView microscopy allows. Importantly, IsoView affords us the ability to perform truly three-dimensional analysis of fast cellular dynamics and neuronal activities across an entire animal and yet preserve sub-cellular resolution and temporal precision to key in on individual cells locally. With the combination of high temporal resolution, high spatial resolution, and large physical coverage, we anticipate that IsoView imaging will open doors to an array of live-imaging applications ranging from developmental systems biology to systems neuroscience.

Explore further:

IsoView video: Whole-animal functional imaging of a Drosophila embryo

IsoView video: Long-term, high-speed timelapse IsoView recording of Drosophila embryo development

Fore more information:

Chhetri, R. K. et al. Whole-animal functional and developmental imaging with isotropic spatial resolution. Nat. Methods 12, 1171–78 (2015), doi:10.1038/nmeth.3632

References:

1. Huisken, J., Swoger, J., Del Bene, F., Wittbrodt, J. & Stelzer, E. H. K. Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305, 1007–9 (2004).
2. Keller, P. J., Schmidt, A. D., Wittbrodt, J. & Stelzer, E. H. K. Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science 322, 1065–9 (2008).
3. Chen, B.-C. et al. Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution. Science 346, 1257998 (2014).
4. Swoger, J., Verveer, P., Greger, K., Huisken, J. & Stelzer, E. H. K. Multi-view image fusion improves resolution in three-dimensional microscopy. Opt. Express 15, 8029–42 (2007).
5. Wu, Y. et al. Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy. Nat. Biotechnol. (2013).
6. Ahrens, M. B., Orger, M. B., Robson, D. N., Li, J. M. & Keller, P. J. Whole-brain functional imaging at cellular resolution using light-sheet microscopy. Nat Methods 10, 413–420 (2013).
7. Lemon, W. C. et al. Whole-central nervous system functional imaging in larval Drosophila. Nat. Commun. 6, 7924 (2015).
8. Chhetri, R. K. et al. Whole-animal functional and developmental imaging with isotropic spatial resolution. Nat. Methods 12, 1171–78 (2015).

Thumbs up (8 votes)
Loading...

Tags: , ,
Categories: Research