In the future diabetics might benefit from getting insulin-regulating beta cells transplanted into their body because their own beta cells are destroyed or less functional. However, according to new stem cell research at the University of Copenhagen, the current way of producing beta cells from stem cells has significant shortfalls. The beta cells produced have some features resembling alpha cells.
Beta cells release insulin in your blood, but when you suffer from Type 1 diabetes, you hardly have any of them left in your body. This is because the immune system attacks the beta cells.
The role of insulin is to reduce and regulate the blood sugar level when it is too high. People with diabetes do not have this function, and therefore need insulin injections in order to regulate their blood sugar levels.
Researchers are trying to produce beta cells artificially with the purpose of transplanting them to diabetic patients to regulate their blood sugar. A new research result from the University of Copenhagen and Novo Nordisk recently published in the scientific journal Stem Cell Reports provides a better understanding of how to improve the production of beta cells from human embryonic stem cells.
“At the moment, we can make stem cells develop into something that resembles proper beta cells. Our research shows that the current method produces cells that resemble alpha cells a little too much. However, the research has given us a better understanding of the steps stem cells go through when they develop into beta cells. In fact, we also show that the cells can develop along different paths, and still end up making the same type of beta cells,” says Anne Grapin-Botton, professor at the Novo Nordisk Foundation Center for Stem Cell Biology, DanStem.
Cells individually examined
The researchers have based their work on human pluripotent stem cells, which are able to evolve into any cell type in the body. Using known methods, the scientists analysed about 600 different cells on their path to beta cell differentiation and individually examined the cells to find out how much they molecularly resemble the beta cells.
In doing so, the researchers acquired important new knowledge about the way in which the cells develop and which genes play a role in this development. Notably, it was important that the genes NXK6.1 and MNX1 were activated for the cells to become beta cells in the end.
“This study takes an in-depth look at the molecular mechanisms on the cell level. We are not looking at what the average cells do, as other scientists have previously done – we are looking at all the individual cells. We are doing so in the hope that we can prevent cells from developing in the ‘wrong direction’. This work sheds light on the paths which the cells take in their development and how we human beings develop in the womb,” says Anne Grapin-Botton.
Start but do not complete the process
Alpha cells have the opposite function of beta cells. They must ensure that the body secretes the peptide hormone glucagon into the blood when the blood sugar level is too low. While the alpha cells cause the blood sugar level to rise, the beta cells ensure that it falls. And when the produced cells resemble the alpha cells too much, they are not optimal for treating diabetics.
“The cells definitely start the process of becoming either alpha or beta cells, but they don’t complete it. Here, we need to carry on researching to learn even more about how we can optimise the last step in the development of beta cells,” explains Anne Grapin-Botton.
The study was conducted in cooperation with project leader Christian Honoré from Novo Nordisk, and is supported by Innovation Fund Denmark, the Danish National Research Foundation and the Novo Nordisk Foundation.
Applications are invited for a Research Assistant position in the group of Prof Daniel St Johnston at the Gurdon Institute, University of Cambridge (http://www.gurdon.cam.ac.uk/research/stjohnston). The BBSRC-funded project aims to determine how epithelial cells organize apical-basal arrays of microtubules and how this is controlled by cortical polarity factors. Responsibilities will include establishing a method for the biochemical isolation of microtubule organizing protein complexes and their analysis by mass spectroscopy in collaboration with the Cambridge Centre for Proteomics and the generation of transgenic and mutant flies using CRISPR/Cas9.
Applicants must have a Bachelors or Masters level degree in a relevant area of Biology or equivalent experience. Expertise in protein purification, molecular biology and/or Drosophila transgenesis would be an advantage, although training can be provided where necessary. The post does not require a PhD qualification.
Our paper, like so many scientific findings, was brought about by a beer – or more specifically a discussion over a beer.
“I had a beer with David (Drechsel)” Jochen (Rink) said to me after one of our weekly scientific social events at the MPI-CBG. Over their beers they had discussed the challenges we were having imaging planaria and David had suggested we use Iodixanol as a supplement to increase the refractive index of mounting media – a suggestion which proved to be key to our success. While this particular problem and solution were quite straightforward, getting to the point where we could even recognize the problem and thus seek a solution involved a few more people (and a few more beers!) This is the story of how our paper, which describes a simple and straight forward method to correct for spherical aberrations of live tissues thus enabling significantly improved image resolution and quality in deeper tissue layers, came to be.
Tuning the refractive index of zebrafish cell culture media to RI 1.362 leads to improved signal to noise ratios along the z-axis. (Boothe et al, eLife 2017, https://elifesciences.org/articles/27240)
During my Ph.D. training in cell biology at the University of British Columbia in the laboratory of Jim (Johnson) I became used to thinking of microscopy as a tool rather than a challenge. This changed when I started my postdoctoral work, which focused on imaging cell dynamics during regeneration in planarian flatworms, in Jochen’s lab. Jochen warned me that this would “not be an easy” endeavor and, given how few tools were available for this relatively rare model system, I believed him. Once I started the imaging experiments and realized it was not possible to see any nuclear structure beyond the outermost cell layer however, I started to understand just how difficult the task I had taken on was. I took advantage of the lab’s species collection to obtain and test an unpigmented planarian species and exhausted the resources of our well-equipped light microscopy facility but the epithelium still seemed to act like a black-out curtain. At this point in time I did not have a well-developed understanding of optics in complex tissues however with the help of MPI-CBGs Moritz (Kreysing) and his student Alfonso (Garcia) I began to understand why a lack of pigment does not automatically mean that a tissue becomes optically clear. One of Moritz’ projects had seen a similar “black-out” effect when imaging dense retinal tissue and he had been able to overcome this challenge and image the deeper tissue layers by tuning the refractive index of their mounting media. While this was a bit different from what we were looking to do, as their work focused on fixed tissues, their results did suggest that the problem we were having could be caused by a significant difference in the refractive indexes of the planarian tissue and the aqueous mounting medium we were using at this time, and that if this were the case it might be possible to improve our images by tuning the refractive index of our mounting media. What we needed to do seemed clear however we still faced a challenge – while refractive index adjustment is a core component of state of the art clearing techniques in fixed tissues we had to find a component to tune the refractive index of our mounting medium to that of the sample without harming the live specimen.
I started by trying obvious candidates such as glycerol and sucrose but their high osmolality created a lethal environment for planaria. Halocarbonoils, which we tried next, worked well in fixed planaria but their hydrophobic nature made it impractical for an aquatic model system. After many trials and even more errors, I found myself at an institute social event sharing a beer and discussing these failures with Lennart (Hilbert). Lennart was studying DNA structure by live super-resolution microscopy in Nadine’s (Vastenhouw) lab at the time, and used BSA for refractive index tuning. While BSA was a promising candidate for planaria, the rather low refractive index tuning range and the viscosity and stickiness of saturated BSA solutions limited its usefulness. Lennart also found these limitations frustrating and so, while his approach at that time could not solve my problem, I did find myself a companion in the search for a live compatible refractive index tuning media supplement.
The postdocs had rounds of beers and discussions week after week but it was not until (of course) the PI got involved that we had our next breakthrough. At the time of Jochen’s forementioned beer with David we were focusing on epithelial cell dynamics because this was really the only cell type we could image in planaria due to the “black-out” effect. David, who was leading the MPI-CBG’s protein expression facility at the time, suggested over that famous beer we should give Iodixanol a try. Like many others he knew Iodixanol as a density gradient medium. While it was widely used for cell or cell organelle isolation, David was also aware though that the stock solution has a rather high refractive index which meant it might be able to meet our particular needs.
Refractive index tuning of planarian culture media by Iodixanol supplementation leads to a significant improvement of nuclei detection in deeper tissue layers. (Boothe et al, eLife 2017, https://elifesciences.org/articles/27240)
After performing some initial tests it became clear that Iodixanol was indeed the reagent we had been looking for. We were able to image past the first cell layer in planaria and significantly improved the live imaging quality in these specimens. Since we were not aware of any compound with similar properties we were eager to test it in other model systems. The diversity of MPI-CBG provided us with access to a number of different model systems and so we tried to improve live imaging in zebrafish embryos. Although this organism is thought to be easy to image, I knew of Lennart’s frustrations thanks to our earlier beers and was happy to share that there might be something which would help. Since imaging zebrafish was so far already of high quality Iodoxanol supplementation did not lead to the clear “day and night” effect we could observe with planaria. As I am a very self-critical (some would even call it pessimistic) experimentalist I started to doubt the broad applicability of Iodixanol but luckily Lennart has a more optimistic approach to things and just said: “Of course it works, it’s Physics.” – and sure enough it did.
In the end it was the diversity of the institute and the inter-lab interactions which led us to this story. We are happy that together we could establish with Iodixanol a compound which can now compensate for spherical aberrations in vivo and we are eager to hear how it works for the community – ideally over another case of beer!
Applied research team in Cape Town, South Africa, is seeking quick assistance from an adventurous soul who is a specialist in the expansion and differentiation of hESCs into neural progenitors and, ideally, also islet progenitors and hematopoeitic cells. The project is part of a clinical trial and will start in early October. We will provide a stem cell lab (we don’t have a bioreactor) and will cover travel and lodging cost and provide a stipend.
We are looking for a highly skilled and motivated candidate to join our group for a PostDoc position. In the Payer lab (http://www.crg.eu/bernhard_payer), we study epigenetic reprogramming in the mammalian germ line and the effects of ageing on fertility. In this project, which will be performed in collaboration with a fertility clinic, the prospective candidate will study molecular links between ageing and fertility decline in women.
We are seeking a candidate with a strong background in Mammalian Cell Culture, Stem Cell Reprogramming and Differentiation, Epigenetics, Reproduction and Molecular Biology. Excellent candidates from other related fields will also be considered.
Work Environment
Our lab is part of the Gene Regulation, Stem Cells & Cancer Programme at the Centre for Genomic Regulation (CRG) in Barcelona, Spain (www.crg.eu). The CRG is a vibrant International Research Institute with Research Groups working in diverse fields such as Genomics, Cell and Developmental Biology, Systems Biology, Stem Cells, Cancer and Epigenetics. English is the working language.
Eligibility
Candidates can be of any nationality, but must undertake trans-national mobility and must not have resided or carried out their main activity in Spain for more than 12 months in the 3 years prior to the call deadline. Furthermore, applicants working at CRG for more than 3 months before the deadline will not be considered.
Candidates must have a PhD degree from a recognized university, plan to obtain a PhD degree by the time of employment, or have at least four years of full-time equivalent research experience. Candidates who already hold a PhD degree at the time of application are eligible to apply only if they passed their PhD exam (or equivalent) in the four years prior to the call deadline. Exceptions up to 3 years for maternity/paternity leaves and other documented career breaks will be considered.
Candidates must have at least one publication as first author (either in press or published) at the time of the deadline
Candidates must provide two letters of reference
Fellowship
36 months by the INTREPiD Fellowship programme.
Applications are accepted exclusively online through:
We now seek to appoint a Research Technician in Molecular and Cell Biology to complement our existing expertise and fill a vacant position for the final 4 years of the “Cellular thyroid hormone availability: regulation of development and tissue repair, and pathogenesis of degenerative disease” project.
The Molecular Endocrinology Laboratory employs state-of-the-art high-throughput imaging and functional phenotyping, together with next generation sequencing and bioinformatics, in a whole organism and systems biology approach. You will receive comprehensive training in order to provide up-to-date technical expertise in cell culture, investigation of molecular mechanisms and signalling pathways, and skeletal phenotyping. You will also contribute to general administration and management of the laboratory.
Closing Date: Tuesday 3 October 2017 (Midnight BST)
Development often involves the asymmetric partitioning of cellular components to daughters, and this process is crucial for successful gametogenesis. Today’s paper, published in the current issue of Development, explores the cytoskeletal mechanisms of spermatogenesis in different nematode species. We met the multi-lab team behind the work, starting with Diane Shakes (The College of William and Mary in Williamsburg, VA), and then her collaborators André Pires-daSilva(University of Warwick, UK), Gunar Fabig and Thomas Müller-Reichert (Technische Universität Dresden, Germany), and Jessica Feldman (Stanford University, CA).
Diane, can you give us your scientific biography and the main questions your lab is interested in?
Diane Shakes
DS I got my start in research as a high school senior through a special program at NASA-Ames Research Center.There I was paired with a fantastic mentor, Patricia Buckendahl, who has talent for productively incorporating novice young scientists into her research quest which at the time was to understand the fundamentals of bone metabolism and why astronauts were losing bone mass in zero gravity. As an undergraduate at Pomona College, NASA-Ames continued to be my summer research home as I explored the breadth of biology in my coursework. Ultimately, I was captured by the wonders of cell biology and the big questions of developmental biology. It was also during this time that I developed an appreciation of the special insights that can be obtained by studying unusual organisms and cell types.
As a Ph.D. student at Johns Hopkins, I joined the research group of Sam Ward. This choice not only linked me not only to the early community of C. elegans researchers but also immersed me in the exciting research that was going on at the Carnegie Institution, Department of Embryology. In Sam’s lab, I worked alongside postdoctoral fellow Steve L’Hernault to isolate and phenotypically characterize a large collection of spermatogenesis-defective mutants in C. elegans. Through these studies, I developed an appreciation for genetics, a love for microscopy, and a life-long interest in the mechanisms of cell polarity. As I neared the end of my graduate studies, Ken Kemphues had just published his foundational study on the C. elegans PAR mutants, so I was excited to join his lab for my post-doctoral studies. My project was to analyze par-5, which like the other par proteins is required to establish proper asymmetries in the 1-cell C. elegans embryo, and ultimately was found to encode 14-3-3.
When I subsequently established my own lab, first at the University of Houston and subsequently at the College of William and Mary, I decided to use my combined knowledge of C. elegans sperm and oocytes to investigate a pair of C. elegans mutants that had been reported to exhibit both maternal and paternal effect defects.
Penny Sadler
Within my own lab, Penny Sadler discovered that although affected oocytes and sperm were both arresting in metaphase of meiosis I, the sperm continued to develop post-meiotically into anucleate sperm that could nevertheless crawl and fertilize oocytes.And in a fruitful collaboration with Andy Golden and a generous supply of mutants from the Bowerman and Seydoux labs, we showed that these and other mutants with the same phenotype were temperature-sensitive alleles of the anaphase-promoting complex. These studies that came out this work stimulated my interest in the interplay between the various cellular and developmental sub-programs of gamete development and drew me back into the analysis of C. elegans spermatogenesis, particularly in the stages leading up to meiotic divisions. The next set of studies – an analysis of the spermatogenesis-specific events during meiotic prophase – were carried out in collaboration with Diana Chu whose expertise in chromatin complemented my own in the cell cycle and cytoskeleton.
In addition to on-going studies in C. elegans, my group has also started using what we know about gametogenesis in C. elegans as a basis for comparative studies in other nematodes. A phone-call from André Pires da Silva got us specifically interested in the trioecious (male/female/hermaphrodite) species Rhabditis sp. SB347 (now called Auanema rhodensis), a lab cultivable nematode with strikingly non-Mendelian sex ratios. In many ways, these cross-species comparisons are analogous to studying a very informative mutant; but in this case, they help us distinguish highly conserved, fundamental processes from those that have been subject to variation over evolutionary time.
What was known about the cytoskeletal drivers of sperm development and asymmetrical positioning in worms before your study?
DS A conserved feature of sperm development in all organisms is that, following the meiotic divisions, sperm become streamlined by discarding unnecessary cellular components. In the early 1980s, Sam Ward’s group had shown, that in C. elegans, these unnecessary components included both actin and microtubules. This is only possible because nematode sperm motility is driven by a completely different cytoskeletal protein, the major sperm protein (MSP). Subsequent experiments with actin and microtubule inhibitors suggested that actin was more important than microtubules in this process of asymmetric partitioning. Subsequently, the L’Hernault and Titus labs showed that proper partitioning required the non-conventional myosin (myosin VI). Yet, no one had ever gone back to study the stepwise progression of events that underlies this wholesale swap of the cytoskeletal system during sperm development in C. elegans. Were there aspects of the process that could be better understood in light of new studies of asymmetric partitioning? Was the unusual partitioning event in R. sp. SB347 completely novel, or an informative variant of events that happen in all nematode sperm?
André – how did your collaboration with Diane come about, and why are different nematode species such useful models for the evolution of sex and reproduction?
André Pires-daSilva
APS Sex determination is a developmental switch prone to rapid evolution, but the causes and consequences for this pattern of evolution are poorly known. The existence of species with three sexes caught my attention because they are supposed to be extremely rare. In 2004 Marie-Anne Félix published a paper mentioning the free-living nematode strain SB347 (now named Auanema rhodensis), which produces males, females and hermaphrodites. Until that time, other free-living nematode species producing three sexes were not available in culture, or were parasitic nematodes difficult to work in the laboratory. Back in 2009, I contacted Diane Shakes to help me in characterizing the cytology of SB347 spermatogenesis, because we were trying to understand why males of this species generate so few males. This was especially puzzling, since heterogametic XO males should produce XX and XO progeny in equal proportions. However, we observed mostly XX progeny only. I contacted Diane because of her expertise in cell biology of C. elegans spermatogenesis and her recent interest in comparative work.
Gunar – I understand that an interest in C elegans sperm mutants brought you, Anna and Thomas into the collaboration?
Gunar Fabig
GF As a PhD student, I am working in the lab of Thomas’ on chromosome segregation in C. elegans male meiosis. Our lab has a strong expertise in live-cell imaging and electron microscopy. So, some years ago I started to image living C. elegans males by fluorescence microscopy to analyze the dynamics of meiotic chromosome segregation. We also started to characterize wild-type spindles of various stages at the ultrastructural level using electron tomography. During the initial phase of my project, I started to think about a comparison of wild-type and mutant data to study situations of impaired chromosome segregation. At the time, I was aware that Diane had a very interesting paper together with André, in which they characterized male meiotic spindles in Rhabditis sp. SB347 (now A. rhodensis). In this paper, they reported about a skewed sex ratio that was most likely caused by a changed meiotic “program” during male chromosome segregation. So we contacted Diane and André to ask whether they would be interested in collaborating with us on the ultrastructure of male meiotic spindles in Rhabditis sp. SB347.
Thomas Müller-Reichert & Anna Schwarz
TMR At the same time Anna started in my lab to work on her Master’s thesis and I proposed to her that an EM analysis of males of this species would be a very exciting project. She did a terrific job in preparing and analyzing SB347 males. Anna discovered the interesting patterns of organelles partitioning to the respective daughter cells.
Jessica – how did you get recruited, and how did your previous work on non-centrosomal microtubules fit into the story?
Jessica Feldman
JF One of the interests of my lab is to understand the mechanisms underlying non-centrosomal microtubule organization. C. elegans is a particularly good model in which to study this question as microtubule organizing center (MTOC) activity is completely reassigned from the centrosome in dividing cells to another site following mitotic exit. I had been exploring this switch in MTOC activity in a number of different cell types in C. elegans and started to focus on the germline, where MTOC activity is at the plasma membrane of non-dividing germ cells, and at the centrosome of mitotically dividing germ cells or meiotically dividing spermatocytes. I started to film this transition and found that microtubules and microtubule minus end proteins remarkably appeared to move from the centrosome of dividing spermatocytes to the residual body. This behavior appeared to mimic a similar movement of microtubules and microtubule regulators that I had previously seen in embryonic intestinal epithelial cells during their polarization, but due to the geometry of the movement in spermatocytes was much easier to visualize there. I presented this work at a conference that Diane was also attending. I think my live imaging data helped shed light on some of the observations Diane had been making about microtubules in fixed samples. In an incredibly gracious act, Diane contacted me to see if I would like to incorporate my data into this manuscript.
Can you give us the key results of the paper in a paragraph?
DS We knew from our earlier paper that the meiotic divisions of R. sp. SB347 male spermatocytes yielded a 50:50 mix of functional X-bearing sperm and residual bodies containing the other chromosomal complement. However we didn’t understand much about the details of the process or whether this pattern was an oddity of a single species. In fact, no one had described the stepwise process by which C. elegans sperm partition into residual bodies, not only unneeded cellular organelles but also their entire pool of actin and microtubules. In this study, we address all of these questions using the combined approaches of immunocytology, transmission electron microscopy, and live-imaging of GFP constructs. We show the first time that in C. elegans, the microtubules redistribute with their gamma-tubulin ring complexes intact from the centrosome to the sperm-residual body boundary in a process that resembles microtubule shifts in differentiating cells. At the same time, in a variation of normal cell division, actin reorganizes through a combination of cortical ring expansion and clearance from the poles. Relative to these cytoskeletal changes, organelles appear to partition in at least two phases; most partition just after the completion of anaphase chromosome segregation while others partition as the sperm detach from the residual body. In the much smaller spermatocytes of both R. sp. SB347 and its near relatives, the cytoskeletal remodeling events are restricted to the pole of the X-bearing chromosome set. Consequently, a partitioning process that is normally bipolar with two haploid sperm generating a central residual body becomes unipolar and generates one functional sperm and one DNA-containing residual body. Intriguing, this unipolar partitioning process also occurs in the XX spermatocytes of SB347 hermaphrodites. In contrast, partitioning is bipolar in the large spermatocytes of R. sp. SB347’s closest known male/female relative. Taken together, this study reveals two major insights. First, the process by which nematode sperm discard actin and tubulin into their residual bodies may be variations of common cellular and developmental processes. Second, constraints related to spermatocyte downsizing may have contributed to the evolution of a sperm cell equivalents of female polar bodies.
Fixed male gonad from C. elegans, from Figure 2 in the paper
What did the TEM bring to the story?
GF & TM Spermatocytes had to be visualized in whole worms, so we had to perform serial sectioning for this project. Anna mastered this without any difficulties. The beauty about electron microscopy is that one can get very detailed images of cellular organization (e.g. about centrioles, microtubules or the Golgi apparatus). For electron tomography, we prepared whole males of Rhabditis sp. SB347 by applying high-pressure freezing. Males were ultrarapidly frozen to liquid nitrogen temperature, freeze-substituted and embedded them in Epoxy resin. We took overview images of serial sections of several worms and counted the number of different organelles in numerous cells as worms contain many spermatocytes. This information enabled us to quantify the distribution of organelles during various stages of meiotic cell divisions in males.
Thin section EM and 3D models from serial electron tomographic reconstructions, from Figure 3 in the paper
What are the key open questions about the role of microtubules in the asymmetric cell division that makes nematode spermatocytes?
JF To me the most interesting questions about the microtubules in nematode spermatocytes are, 1) how is the centrosome inactivated as an MTOC?, 2) how are microtubules transported to the RB?, 3) what organizes microtubules inside the RB?, and 4) in Rhabditis sp. SB347, what controls the selective inactivation of MTOC activity at only one of the centrosomes? The answers to these questions will not only teach us about spermatogenesis, but will also answer major questions in the field of microtubule organization.
γ-tubulin localization during the separation phase of spermatogenesis in C. elegans. Movie 1 from the paper
What do you think the main evolutionary implications of the work are?
APS Three-sexed species are interesting, because they are probably evolutionary transitions between male/female and male/hermaphrodite mating system as known in C. elegans. They may help us understand in how mating systems evolve, a long-standing question in Evolutionary Biology. In this paper, we showed the mechanisms of ‘how’ males generate non-functional nullo-X sperm. This is one of the few examples in the literature describing cellular mechanisms of how heterogametic animals generate progeny of a single karyotype. There are examples for other nematodes and animals in other phyla in which crosses between XX and XO individuals generate mostly only XX progeny. Perhaps they use similar mechanisms as SB347, and this paper provides the foundation for testing this hypothesis. At the moment, however, we do not understand ‘why’ SB347 males get rid of their ‘male-making sperm’. According to evolutionary theory, this would happen if sibling matings are common. Unfortunately, we do not know much about the ecology of SB347 to test this.
DS From my perspective as a cell and developmental biologist, I think that this work highlights how a conserved set of cellular and developmental sub-programs can be co-opted for different outcomes. This study suggests that highly unusual process of partitioning microtubules into a residual body is not a novelty of nematode spermatogenesis but rather a variation of a common process during which differentiating cells lose their centrosomal microtubules as they establish a distinct population of non-centrosomal microtubules. Similarly, we show that the step-wise progression by which nematode sperm partition actin into the residual body exhibits many similarities to actin remodeling during the transition from anaphase to cytokinesis. Thus I predict that much of the underlying molecular machinery will be evolutionarily conserved with the notable exception of a novel regulator or altered feedback loop. Yet because these processes within nematode sperm are indeed a bit extreme, their analysis will yield important insights into related cellular and developmental processes.
Actin changes in R. axei spermatocytes, from Figure 5 in the paper
What next for the Shakes lab?
DS Our on-going analysis of R. sp. SB347 continues to surprise and delight us. There is still much to be learned about the molecular mechanisms of this partitioning event as well as other oddities of SB347 meiosis. For example, we also have a paper coming out this month in Developmental Biology, in which we describe how this clade evolved a distinct solution for acquiring hermaphrodite self-fertility, namely the simultaneous rather than sequential production of oocytes and sperm. So in the R. sp. SB347 realm, we have many interesting avenues to explore. At the same time, the C. elegans focused cohort in my lab are hard at work gleaning new insights from the existing collection of spermatogenesis mutants, some of which have been languishing in our liquid nitrogen tanks since my graduate days.
Any plans for future collaborations?
Yes, Andre and Diane’s lab are collaborating on a project that describes differences in meiosis in SB347 males, females and hermaphrodites, and the labs of Andre, Diane and Thomas are collaborating on a project to identify the signal that determines the directionality of the asymmetric division of the SB347 male spermatocytes.
Anything else you would like to add?
Ethan Winter
DS One voice that is missing in this interview is the lead author Ethan Winter, a former undergraduate honors student in my lab who helped spearhead this project through his cytological studies of R. sp. SB347 and its near relatives. Ethan continued on to Harvard to pursue a Ph.D. in Chemical Biology. Not only was he brilliant, hard-working, and tenacious, but he was also kind, patient, and possessed a wonderful quirky sense of humor. We all predicted that he was on track to develop into a beloved professor. Sadly, Ethan passed away last October (2016). I hope that this paper serves at least in a small way as a tribute to his scientific accomplishments and his too-short life.
We are seeking a highly motivated and collaborative Laboratory Research Scientist in the area of human embryology and stem cell biology to join Dr. Kathy Niakan’s laboratory. The lab has identified several signalling pathways that may be operational in the human embryo to regulate the establishment or maintenance of pluripotent epiblast progenitor cells that can be coaxed to self-renew indefinitely as embryonic stem cells in vitro. The role will involve further characterising the function of these signalling pathways in the human embryo and testing their sufficiency to establish alternative human embryonic stem cells.
The successful candidate is likely to be collaborative, energetic, focused, and productive individual. Excellent organisational, analytical, and communication skills are essential.
Dr Niakan’s laboratory focuses on understanding the mechanisms of lineage specification in human embryos and the derivation of novel human stem cells. The post holder will report directly to the Group Leader, Kathy Niakan. Details of research projects currently being undertaken can be seen at: http://www.crick.ac.uk/kathy-niakan
PROJECT SUMMARY
The pluripotent epiblast of the early human embryo has the unique potential to give rise to the entire fetus in vivo and can self-renew indefinitely as embryonic stem cells (hESCs) in vitro. Understanding how this lineage is established is of fundamental biological importance and has significant clinical implications for both infertility treatment and the use of hESCs to treat various diseases. We have identified several components of key signaling pathways that are highly expressed in the epiblast, and whose activity leads to the proliferation of these pluripotent cells in vivo. Based on our preliminary data, we have been awarded an Insight to Innovate Grant to follow up these observations, in collaboration with commercial organisations.
The aim of this project is to further characterise how these factors regulate human pluripotency and embryogenesis. We also seek to establish novel culture conditions for human pluripotent stem cells by modulating these signaling pathways during stem cell derivation. In collaboration with our commercial partners, we will evaluate if these conditions better maintain pluripotency of existing hESCs, and how this may translate to improved derivation of induced pluripotent stem cells (iPSCs) or more efficient directed differentiation protocols.
Please note: all offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.
A postdoctoral research position is available starting in the first half of 2018 for a biologist to work with Asst. Prof. Timothy Saunders’ group at the Mechanobiology Institute, Singapore (http://labs.mbi.nus.edu.sg/mod/). The Saunders lab studies the fundamental processes shaping organs and tissues during development.
One major focus in the lab is myogenesis in the developing Zebrafish embryo. We are part of a major five-year grant focused on understanding non-canonical roles of receptor tyrosine kinases in cell regulation, including in vivo. The project will involve live-imaging myogenesis on confocal and light-sheet microscopes and developing detailed four-dimensional maps of myotome development. Reagents, including optogenetic and novel live-markers, will need to be created as part of the project.
Candidates should have extensive experience in at least two of: (1) Zebrafish genetics and general fish capabilities; (2) Biochemistry and construct design; and (3) Quantitative imaging methods and image analysis. The candidate must be prepared to learn the necessary skills to perform this challenging project.
The project is in collaboration with Prof. Philip Ingham, at the Living Systems Institute, Exeter, UK and Nanyang Technological University, Singapore. Opportunities are available for lab placements in Prof. Ingham’s lab as part of the project. This offers an opportunity for a dedicated researcher to develop a truly interdisciplinary collaboration.
Interested candidates should contact Timothy Saunders (dbsste@nus.edu.sg), including a CV.
Location: Institut Curie, located in the center of Paris, is an internationally renowned institution bringing together physicists, chemists, biologists, bioinformaticians and clinicians.
Position:
Jean-Leon Maitre, head of the “Mechanics of mammalian development” team (science.institut-curie.org/team-maitre/), is seeking a motivated postdoc with a strong interest in interdisciplinaryresearch.
The candidate will study the morphogenetic events occurring before implantation of the embryo, which requires an approach at the interface between biology and physics (Maître et al, Nat. Cell Biol., 2015; Maître et al, Nature, 2016; Maître, Biol. Cell, 2017). The candidate’s work will include developmental biology techniques with recovery, culture and manipulation of mouse embryos; biophysical techniques such as high-resolution microscopy and micropipette manipulation of embryos; data and image analysis.
Skills:
Prior experience with mouse, advanced microscopy, molecular biology and/or image analysis will be extremely valuable, but on-the-job training will be additionally provided. The ideal candidate should feel comfortable working in an interdisciplinary and international environment.
The position is funded by the ERC for 24 months initially.
Interested candidates should contact jean-leon.maitre@curie.fr
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