The Craft lab at Boston Children’s Hospital and Harvard Medical School is looking for an outstanding, highly motivated postdoctoral fellow to join our developmental biology and pluripotent stem cell-based team.

We established directed differentiation protocols to generate distinct articular and growth plate-like cartilage lineages from human and mouse pluripotent stem cells (Craft et al., Development 2013; Craft et al., Nature Biotech 2015). NIH and foundation funded projects in our lab include investigating mechanisms of articular chondrocyte lineage commitment and stability of this fate through deep sequencing and functional assays, specification and characterization of joint progenitor cells using newly generated fluorescent reporter lines, translational/preclinical experiments of cartilage repair in large animals, and developing iPSC models of congenital cartilage disease. Collaborative projects with Harvard faculty include studies of how modifications in regulatory elements of GDF5 impact gene expression and differentiation of joint lineages (with Dr. Terence Capellini, Harvard University), and evaluating the cartilage and tendon-inducing functions of small molecules and their associated signaling pathways (identified by Dr. Jenna Galloway, Massachusetts General Hospital, through zebrafish screens) in embryonic stem cell (ESC) differentiation cultures.

Requirements: The successful candidate will have received a PhD or MD/PhD within the past 2 years, a minimum of 3 years laboratory experience including tissue culture, at least one first author publication, and excellent communication skills in English.  Individuals with experience in one or more of the following are encouraged to apply: limb/joint/cartilage or early embryonic development, signal transduction pathways, ESC/iPSCs, single cell RNAseq/programming.

https://hsci.harvard.edu/craft-lab-postdoctoral-fellow

Apply: Interested applicants should email their CV, a cover letter describing their research background/interests, and contact information for three references to april.craft at childrens.harvard.edu

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Press release from Development. You can also read the Research Highlight for this article.

Researchers have identified the hormone that causes sex reversal of medaka fish growing in high temperatures. This study from the Instituto Tecnologico de Chascomus (INTECH) in Argentina is the first to report that the brain is involved in the masculinization of females, which has implications for fish populations as temperatures rise. The research has just been published in the scientific journal, Development.

Dr Juan Fernandino led the team investigating sex reversal, a phenomenon seen in some species whereby environmental conditions, such as high temperatures, cause genetically female fish to develop testes rather than ovaries. Now, researchers show for the first time that the brain can influence this process. “In the past, sex determination studies were specially focused on the gonad, probably because in genetic sex-determining genes are initially active in the gonad, driving the development of the testis,” explains Fernandino, “I was surprised at how long it took us to change our focus that sexual determination begins exclusively in the gonad.”

After identifying the hormone produced in fish growing in high temperatures, the researchers used CRISPR/Cas9 genome-editing technology to block the ability of cells to detect it. Importantly, this stopped genetic females developing into males, “I was happily surprised that using gene editing we obtained a complete suppression of masculinization induced by temperature” says Fernandino, “our results highlighted for the first time the participation of the brain as a transducer of environmental stressors, directing development of the testis in genotypic females.”

Identifying how sex reversal occurs has important implications for how some species of fish reproduce. Increasing temperatures and warmer waters might result in more male fish and fewer females. Not only would this affect the ability of fish to reproduce, but also the repercussions on fish populations might have knock-on effects for the ecosystem and fishing industry. “Understanding the molecular mechanisms behind heat-induced masculinization is of great importance for controlling sex ratios in aquaculture and to predict the potential effects of climate change in an important group of animals,” adds Fernandino.

The full study, “The central nervous system acts as a transducer of stress-induced masculinization through corticotropin-releasing hormone B” appears in the journal, Development.

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The Maehr Laboratory is seeking a highly motivated postdoctoral research fellow to investigate the molecular basis of immune syndromes and immune cell development.

The applicant will be taking on experimental and/or computational projects in a collaborative cross-disciplinary group. Envisioned projects integrate pluripotent stem cell differentiation approaches with applied developmental immunology approaches and functional genomics, to decipher the molecular underpinnings of human immune syndromes such as autoimmunity and immunodeficiency. In addition, the collaborative project will apply disease models, single-cell omics, and computational analysis strategies based on data-integration and machine learning.

The dynamic and collaborative Maehr lab is embedded in the cutting edge research environment of the Program in Molecular Medicine and Diabetes Center Of Excellence at the University of Massachusetts Medical School. Please visit our webpage for full list of affiliations and more information about us: http://maehrlab.net/ (web) and @MaehrLab (twitter)

Candidates should possess a Ph.D. and have a strong background in immunology, developmental and/or computational biology. Experience with stem cell differentiation, bioengineering and/or computational approaches is desirable. Excellent communication, writing, and collaboration skills are essential.

Interested candidates should email a cover letter and CV to Dr. René Maehr (rene.maehr@umassmed.edu). 

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This interview, the 60th in our series, was recently published in Development

In development and during regeneration in adults, muscle fibres develop from muscle progenitor cells, and the proliferation, differentiation and fusion of these progenitors needs to be tightly controlled and co-ordinated. A new paper in Development studies the role of the mTOR protein in this process using genetic deletions that target either of the two protein complexes mTOR functions in. We caught up with lead author Nathalie Rion and her supervisor Markus Rüegg, Professor of Neurobiology at Biozentrum, University of Basel, to find out more about the work.

Markus, can you give us your scientific biography and the questions your lab is trying to answer?

MR Even as a young teenager I was fascinated to learn about discoveries of the molecular mechanisms underlying the formation and function of the nervous system. During my PhD studies at the University of Zurich, I characterized cell adhesion molecules that are important for axonal pathfinding, and during my postdoctoral work at Stanford University I cloned and functionally characterized splice isoforms of the protein agrin, the key inducer of neuromuscular synapses. For more than 25 years since then I have been a group leader at the Biozentrum, University of Basel.

My laboratory has also evolved during these 25 years. From initially studying mechanisms underlying neuromuscular synapse formation, we are now interested in how skeletal muscle can adapt to changes in the environment. It is well known that skeletal muscle, which makes up to 50% of the entire body weight, adapts rapidly to changes. For example, if muscle is not properly innervated, it loses muscle mass. Similarly, at old age, muscle mass is lost in a syndrome called sarcopenia. However, the molecular mechanisms driving these adaptive processes are not well understood, and we are trying to better understand them by using mice and tissue culture experiments. In particular, we discovered that changing signalling of the protein mammalian target of rapamycin (mTOR) in skeletal muscle affects the development of sarcopenia in mice. Another interest in the laboratory is to try to develop treatment options for a very severe, rare congenital muscular dystrophy, called MDC1A or LAMA2 MD. In this disease, the muscle fibres cannot withstand the mechanical load that occurs during contraction and, as a result, they degenerate. Over the years, we have developed small linker proteins that are capable of stabilizing the muscle fibres and thereby counteracting this severe muscular dystrophy in mice.

In summary, the common theme of the laboratory is the attempt to understand pathological states of skeletal muscle and its innervation by motor neurons, and to develop approaches to counteract them.

Nathalie: how did you come to join the Rüegg lab, and what drives your research?

NR As a young student, I did not have a defined plan for my future and rather followed my curiosity and my fascination with nature and what is still to be discovered. I was an undergraduate at Biozentrum, and like all students there, I was introduced to all the research groups of the institute. The course of Markus and his group instinctively drew my attention and subsequently formed my future career. He is extremely motivated and engaged in supporting and educating students. I was very fortunate to have the possibility to learn, work and develop in his lab, not only professionally but also on a personal level. My research was also greatly driven by my mentor and supervisor, Dr Perrine Castets. She is an extremely talented, hard-working and dedicated researcher and teacher who inspired and motivated me during the past 8 years. We worked very closely together in Markus’s lab and supported each other in our projects. Therefore, I would like to emphasize her great contribution to this work and thank her for all her support.

Prior to your work, what was known about the role of mTOR-and the relative roles of its mTORC1 and mTORC2 complexes in muscle development?

NR & MR Published work mainly investigated the role of mTORC1 and mTORC2 with shRNA-mediated knockdown experiments in cultured myoblasts from a mouse cell line (C2C12). These results suggested that mTORC1 had a role in muscle differentiation, but there were others who provided evidence that this function was largely mTORC1-independent and mTORC2-dependent. Another important piece of work showed that activation of mTORC1 was involved in the ‘priming’ of quiescent satellite cells for activation. This work, however, did not study its role in regeneration or in myogenesis. In addition, previous work from our laboratory using Cre-drivers specific for skeletal muscle fibres showed that depletion of raptor (an essential component of the mTORC1 complex) but not of rictor (an essential component of the mTORC2 complex) during muscle growth led to myopathy. It was thus important to understand the role of raptor and rictor during myogenesis and during regeneration in the adult muscle.

Can you give us the key results of the paper in a paragraph?

NR & MR By depleting raptor or rictor in embryonic muscle progenitors, we show that mTORC1, but not mTORC2, deficiency in developing muscle impairs embryonic myogenesis without completely abolishing it. Inactivation of mTORC1 in muscle stem cells impairs injury-induced regeneration of the adult tissue due to a delay of activation and commitment into the myogenic lineage, as well as proliferation deficits. In vitro, raptor depletion in myoblasts slows down proliferation, differentiation and fusion. Nevertheless, muscle progenitors deficient of mTORC1 signalling contribute to the formation of skeletal muscle.

Do you think mTORC1 is doing the same thing in embryonic and regenerating adult muscle?

NR & MR This is a difficult but very interesting question. From our work, one can conclude that the cell-intrinsic function of raptor in the embryonic and adult stages is similar. Proliferation of raptor-depleted cells, isolated from embryonic or adult skeletal muscle, is strongly impaired, and of course proliferation is an important process in embryonic myogenesis and adult muscle regeneration. However, the extracellular environment is quite different between embryos and adult muscle. Hence, differences in extrinsic factors could also affect the dependence of satellite cells on mTORC1 signalling.

How do you think muscle progenitors that lack mTORC1 are able to form myofibres?

NR & MR Removal of raptor does not completely abolish protein synthesis. Hence, a low, basal level of protein synthesis may suffice to allow some regeneration and myofibre formation in the absence of mTORC1 signalling. Thus, non-mTORC1-dependent pathways, such as the Mnk1/Mink2 kinases, could become active. It would be interesting to investigate whether there is such a compensatory mechanism and to investigate the possible reasons for this.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

NR Thinking back, I can still remember the first time I performed FACS sorting from embryonic muscle tissue as one of my biggest eureka moments. It was so fascinating and exciting for me to see that it is possible to isolate, analyze and culture living cells from such a tiny amount of tissue, and that the cells survive such a long and harsh procedure.

And what about the flipside: any moments of frustration or despair?

NR Our embryonic work required us to set up timed-matings before the actual experiment could be initiated. Therefore, the most challenging part of this project was to deal with the long timelines and associated limitations, including the small amount of harvested muscle tissue arising from our Rptor knockout mouse model. My biggest despair was when, after these long planning phases, the females were not gestant, no Rptor knockout embryos were among the offspring, or an experiment just failed. However, I learnt from such unfortunate events, and still had a great time working with mouse models: they allowed me to analyze the role of mTOR in myogenesis at both an embryonic and an adult stage.

So what next for you after this paper?

NR I highly enjoyed doing laboratory research for the past 8 years, and I was very fortunate to work on such a fascinating project. After completing my PhD studies and this project, I wanted to change my point of view in science and learn about the journey of medicines from research and development in pre-clinical and clinical studies towards marketing authorization. Today, I am proud to be an employee at SFL Regulatory Affairs & Scientific Communication GmbH, here in Basel, in the field of regulatory affairs. I am very happy to implement my knowledge and experience from research, scientific writing and project management in the support we provide to clients, ranging from regulatory strategy and advice on the development of healthcare products to hands-on operational support during product registration and postmarketing activities.

Where will this work take the Rüegg lab?

MR The work now published in Development was the first time we looked at myogenesis per se and examined the function of satellite cells (the adult muscle stem cells). Satellite cells are also the cells that allow muscle fibres to fully regenerate after an injury, and we found that mTORC1 signalling is important for the regenerative process. Now, we would like to study the molecular processes that are involved in muscle regeneration in general, with the aim of understanding why regeneration is often hampered in the context of muscular dystrophies. Although muscular dystrophies are primarily muscle-degenerative diseases, successful regeneration of muscle is of fundamental importance to overcome some of these degenerative processes. Recent evidence indicates that in many muscular dystrophies, including MDC1A/LAMA2 MD, muscle regeneration is severely impaired.

For me, cooking and baking are quite similar to performing an experiment

Finally, let’s move outside the lab – what do you like to do in your spare time in Basel?

NR I play the piccolo (a special flute) at the Carnival of Basel, which in 2017 was added to UNESCO’s list of Intangible Cultural Heritage. Between February and March each year, Basel transforms into a large, jovial festival with costumed carnivalists, concerts and parades of fife and drum cliques, lanterns and wagons for 72 h.

Besides playing music and enjoying sports, I am a passionate baker and cook, especially in the company of my family and friends. For me, cooking and baking are quite similar to performing an experiment. Both procedures are based on the following of a ‘recipe’ with described components and processes. However, the understanding and feeling for the individual steps and ingredients determine the success of the outcome.

MR As I mainly sit at my desk during work, I need to get some physical challenges. I therefore enjoy all kinds of sports activities, my favourites being jogging, bicycling, hiking in the summer and skiing in the winter.

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Each year The Royal Society, the world’s oldest national scientific institution, elects a new set of Fellows (both UK-based and ‘Foreign Members’). This year, among 62 distinguished researchers from across the scientific disciplines, four developmental biology and stem cell researchers were named, and one name in particular delighted the Development office…

James Briscoe, who joined Development as Editor-in-Chief last year and who has also served as Director on the board of The Company of Biologists, is now James Briscoe FRS! James’ lab at The Crick in London works on the molecular and cellular mechanisms of embryonic development with a particular focus on the developing spinal cord. You can hear more about his life in science in Katherine Brown’s Development interview, and his plans for Development in his inaugural editorial. Congratulations James!

The 2019 list also includes:

• Richard Harland (UC Berkeley), whose lab works on early vertebrate development using Xenopus
• Elaine Fuchs (Rockefeller, NY), whose lab works on adult skin stem cells
• Hans Clevers (Hubrecht Institute, NL), whose lab works on adult stem cell-based organoids

Congratulations to all three, and the rest of the new FRS family.

(1 votes)

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Polyploidy is a conserved and frequently occurring phenomenon whose impact on organismal health and disease is poorly understood.  This first symposium focused on Polyploidy was organized by Don Fox (Duke University), Vicki Losick (MDI Biological Laboratory), and Adrienne Roeder (Cornell University), and took place at the MDI Biological Laboratory in Bar Harbor, Maine on October 13-14, 2018.  The meeting successfully appealed to a wide-range of scientists at different stages of their career from across US and abroad.

The sessions covered research using diverse model systems, including the fruit fly, worm, plant, fungi, zebrafish, and mammalian models.  The meeting topics included the role of polyploidy in organ development, tissue repair and regeneration, cell cycle and chromosome segregation fidelity, size control, and infection and disease.   The talks and posters revealed remarkable commonalities across these systems and several themes emerged.   First, although polyploidy comes in many forms, from whole genome duplication throughout the organism to increased DNA content in specialized mononucleate cells, multinucleate cells, or syncytia, it is almost universally associated with an increase in cell or organismal size.  Adding to the complexity, polyploid cells often alter genome copy number either through amplification or underreplication. The advancement of high resolution imaging and single cell sequencing are now providing mechanistic insight into how polyploid cells increase size and alter their genome.

A second theme is that polyploidization often occurs in response to wounding and tends to increase with age but depending on the organ/tissue can be either beneficial or detrimental to regenerative potential.  A third theme is that mechanical signals, likely from the extracellular environment can induce polyploid cell growth, regulating organ development and speed of wound healing.  In addition, many talks revealed that evolutionarily conserved cell cycle regulators are instrumental in producing polyploid cells and regulating their genome integrity. Polyploidy can prevent cell cycle re-entry, which can be advantageous in blocking tumorigenesis or cell death. While these are in some sense “scheduled” polyploidization events that the organism itself induces, “unscheduled” cellular polyploidy events often lead to disease. In the keynote talk, David Pellman (HHMI/Dana Farber) discussed his model that defects in the nuclear envelope of micronuclei explain how an “unscheduled” genome duplication leads to chromothripsis (a chromosome that appears shattered and randomly stitched back together), which sequencing has shown is very common in human cancers. Infections by parasitic nematodes can trigger the formation of polyploid cells in plant roots and ploidy of infectious yeast strains vary in clinical isolates. One of the conclusions the meeting, which was particularly emphasized by Jeff Doyle (Cornell University), was just how many important open questions remain about polyploidy, indicating there is plenty of exciting research to be done on this emerging field. The next Polyploidy symposium is set for 2020 or 2021.

(5 votes)

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A fundamental question in biology is how cells communicate to fashion and repair complex biological structures and tissues.  It is well established that cells communicate through biochemical cues.  However, compelling evidence suggests that cells and tissues of all types use ion fluxes to communicate electrically as well.  In addition, it is now clear that this method of communication is essential to proper development, regeneration, cancer suppression, and tissue homeostasis.  The field of developmental bioelectricity focuses on the regulation of cell-, tissue-, and organ-level patterning and function, as the result of endogenous electrically-mediated signaling events.  While endogenous ionic phenomena and the effects of applied fields have been known for decades, there has been an explosion of new molecular-level and computational work in the past 5–10 years to establish this new interdisciplinary field, which is ripe for its first focused meeting.

We are delighted to announce that there will be a satellite symposium on Developmental Bioelectricity (see https://www.developmentalbioelectricity.org/), immediately before the 78^th Annual Society for Developmental Biology Meeting in Boston, Massachusetts this summer.  This one-day symposium will take place on July 26^th, from 9:00am to 4:00pm, and individuals registered for the Annual SDB Meeting can attend this symposium without paying an additional registration fee.  Our current speakers include Emily Bates (University of Colorado), Wendy Beane (Western Michigan University), Laura Borodinsky (University of California Davis), Matthew Harris (Harvard University), Xi Huang (University of Toronto), Michael Levin (Tufts University), Kelly McLaughlin (Tufts University), Harry McNamara (Harvard University), Nestor Oviedo (University of California Merced), and Min Zhao (University of California Davis).

We still have a few spots left for talks from graduate students and post-doctoral fellows!  If you are interested in giving a short talk at this Satellite Symposium on your research/on the work you are presenting at the poster session of the Annual SDB Meeting, please contact us at bioelectricity@tufts.edu

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We are seeking potential candidates with an impressive track record and a compelling vision for independent research in the broad area of stem cell and developmental biology. DanStem’s current mission is to achieve a quantitative understanding of cell behavior during development, homeostasis and disease, and we particularly encourage letter of interests from scientists who have quantitative or computational facets to their future plans.

The Novo Nordisk Foundation Center for Stem Cell Biology (DanStem) addresses fundamental research questions in stem cell and developmental biology and has activities focused on the translation of promising basic research results into new therapeutic strategies for cancer and chronic diseases. While opportunities exist for translation, the primary criteria for membership in DanStem is excellence in fundamental basic research. DanStem is a vibrant, internationally diverse and ambitious research center with state-of-the-art facilities located at the Faculty of Health and Medical Sciences, University of Copenhagen. The setting is ideally suited for seamless collaboration and exchange with other centers and departments of the Faculty and Copenhagen science community. Learn more about DanStem at https://danstem.ku.dk/.

As a group leader, you will initiate a new independent research program within the field of stem cell and developmental biology. DanStem provides a generous support package for the group leader, which includes salary of the group leader, support to other personnel, consumables and modern laboratory and office facilities. The group leader is expected to complement this budget through other national or international grants and/or industrial collaborations. In addition, the group leader is expected to engage in multidisciplinary research collaborations with other DanStem research groups other research groups within the Copenhagen area.

Your background includes a PhD or equivalent degree, postdoctoral training and an experience-appropriate track-record of publications in top journals. International mobility, such as training in high-quality institutions and universities globally will be valued.

We offer

• A generous package, including salary, support to other personnel, consumables.
• Access to cutting edge technologies through shared-resource platforms and staffed expertise in flow cytometry, genomics, imaging, stem cell culture and data analytics.
• A vibrant scientific community, with strong internal synergy, situated for easy collaboration and exchange with other centers and departments at the University of Copenhagen and the greater Danish scientific and clinical communities.
• Opportunities for the development of basic research discoveries into translational research
• Affiliation to the Copenhagen Bioscience PhD Program for international PhD student recruitment and training
• Support from management and DanStem fora with regard to career path and development.
• A local Administration and Research Support unit to support with economy, HR, Research and Innovation.

Inquiries are welcome to Henrik Semb (semb@sund.ku.dk).

Letter of interest

Letters of interest should include a cover letter summarizing the applicant’s career, past research accomplishments (max 1 page) and future plans (max 5 pages), a CV and a list of publications (with up to five of the most significant publications indicated), and names of three references.

The University of Copenhagen International Staff Mobility Office offers assistance and guidance with regard to relocation, e.g., housing, spouse program, pension, taxes, etc. For more information, visit the ISM website:  https://ism.ku.dk/.

DanStem highly values diversity and encourages people of all backgrounds to submit letter of interest, in English to GL-2019@sund.ku.dk.

The closing date for letters of interest is August 1, 2019

Founded in 1479, the University of Copenhagen is the oldest university in Denmark. It is among the largest universities in Scandinavia and is one of the highest ranking in Europe. The University´s six faculties include Health Sciences, Humanities, Law, Science, Social Sciences and Theology. www.ku.dk

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A postdoctoral position is available in the Bush lab bush.ucsf.edu at the University of California, San Francisco to study the cellular basis of morphogenesis using live imaging, mouse genetic, and iPSC and ESC approaches. Our dynamic team focuses on understanding basic mechanisms of signaling control of morphogenesis particularly as related to human structural birth defects. The position is in the collaborative UCSF Department of Cell and Tissue Biology and Program in Craniofacial Biology, located at the UCSF Parnassus Heights campus, in the center of San Francisco. UCSF offers an outstanding developmental biology community, access to cutting edge technologies and a supportive working environment. Candidates with a Ph.D. degree in a biological science and research experience in molecular biology, genetics, biochemistry, or live cell or live embryo imaging should submit a C.V. and names of at least 2 references via email to: jeffrey.bush@ucsf.edu

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