The Blanchoud lab (University of Fribourg) and the Tiozzo lab (CNRS, Sorbonne University) are offering one year SNF funded post-doc position on a project that aims to survey horizontal gene transfers in Tunicates, the sister group of vertebrates. In particular, the candidate will perform a coherent and integrated analysis of all currently available genomic, transcriptomic and proteomic data to estimate the extent of functional foreign genetic material and their potential role in these marine chordates.
We are looking for a highly motivated bioinformatician with the following qualifications:
PhD degree in Bioinformatics, Computer Science, or a related field
Strong experience in the development of bioinformatic analysis workflows
Proficiency in suitable programming languages (e.g. Python, R)
Familiarity with HPC systems
Background in evolutionary biology and/or biochemistry would be a plus but is not required
The successful candidate will start at the latest by February 15th 2020, for a duration of 12 months. The project will be mainly held in Fribourg (Switzerland). However, short-term mobility to Villefranche-sur-Mer (France) will be considered.
Please submit your letter of interest, CV, references, and a relevant sample of code by email to Simon Blanchoud (simon.blanchoud@unifr.ch) and/or Stefano Tiozzo (tiozzo@obs-vlfr.fr).
3 year-POSTDOC + Starting grant (OPENING-SOON BEATRIU de PINOS program) to join our lab on EvoDevoGenomics in BARCELONA
We are seeking candidates to join our lab to study our favorite chordate model Oikopleura dioica, in which we are currently interested in chordate development, specially heart and muscle, and the impact of gene loss on the evolution of gene regulatory signalling networks. Click here for a tour “A day in our lab” posted in The Node
We have also engaged a new EcoEvoDevo line investigating if the developmental mechanisms of marine embryos are ready to respond to climate change, including biotoxins derived from algal blooms. Click here for a tour on this new EcoEvoDevo adventure.
Our approaches include single-cell RNAseq, Embryo microinjection, RNAi, Confocal-Microscopy, Bioinformatics and soon CRISPR
DEADLINE call: February 3rd 2020 (contact for enquiries as soon as possible canestro@ub.edu)
REQUIREMENT: to have defended the PhD within the period January 1st 2012 – December 31st 2017; 2-years of postdoctoral experience; less than 12 months living in Spain the last 3 years.
DURATION: 3 years: starting not later than February 2021 (to be confirmed)
FUNDING: 132.300€ total gross salary for 3 years + 12.000€ research funds
CONTACT: Interested candidates, please send an email to Cristian Cañestro (canestro@ub.edu), including a brief letter of interest, a brief CV, including list of publications with their impact and quartile, and technical skills (specially those related with our approaches) all together in ONE single pdf file.
The discipline “Evo-devo” studies the developmental basis of morphological evolution. In the field, some original animal models are emerging as interesting model organisms, enriching the knowledge in the field more and more.
In the DECA team (Développement et évolution du cerveau antérieur, in French) we use an Evo-devo approach to study the developmental mechanisms responsible for brain evolution. Adaptation to new environments brings along changes in brain morphology and function, and these changes are more striking in organisms adapted to extreme environments. A beautiful example that illustrates this topic is the model species used in our lab, the Mexican fish Astyanax mexicanus (teleost). Within the same species there are several river-dwelling populations (surface fish) and other populations adapted to caves (cavefish), living in absolute darkness. Evolution in the caves have led to the total loss of eyes and pigmentation, similarly to many other cave organisms. Since the cavefish embryos initially develop a small eye primordium that then degenerates at larval stages, Astyanax mexicanus has become an attractive model to study the genetic and developmental causes of eyes loss and the mechanisms of sensory compensation.
Figure 1.- Adult cavefish and surface fish morphotypes of Astyanax mexicanus (top left and right, respectively). Chica cave (bottom left) and Micos river (bottom right) in Mexico.
In our lab some hypotheses have been tested in order to explain the regression of the eyes in cavefish, including modifications of midline signaling centers important for eye induction, or “trade-offs” within the neural plate between the eye field and other neural tissues.
Recently we started to wonder how early in embryogenesis we were able to find differences between the two eco-morphotypes. We decided to compare the process of gastrulation in the two Astyanax morphs, to look at the establishment of the axial signaling centers important for brain development. By comparing systematically the expression of key genes involved in gastrulation we found important heterochronic differences in terms of internalization and migration of the precursors of axial mesoderm, the embryonic organizer. At this point we were very proud of ourselves, because we were able to discriminate between surface fish and cavefish embryos already at the onset of gastrulation, just by looking at in situ hybridizations.
We realized that at the end of gastrulation the anterior axial mesoderm, also called prechordal plate, was different in several aspects, particularly when we looked at the expression of dkk1b (an inhibitor of the WNT pathway). In cavefish embryos, expression of dkk1b occurs in cells that were more dispersed than in surface fish, with lower levels of transcripts and with an earlier off-set of expression, suggesting a globally reduced repression of WNT compared to the surface morphotype. In vertebrates, WNT repression is fundamental for the normal development of the forebrain, including the eyes. Through functional test we showed that modified WNT modulation is indeed implicated in the cavefish eye phenotype.
Next, we reasoned that if at the onset of gastrulation there is already a morphotype-specific embryonic patterning, there might be something different even before this step. Since embryogenesis before gastrulation, including the induction of the organizer, is controlled by determinants present in the oocyte before fertilization occurs, we made the hypothesis that differences from gastrulation onwards are could be due to modified synthesis of maternal determinants. Thus we decided to compare through RNAseq the transcriptomes in embryos just after fertilization, when only maternally-provided mRNAs are present (maternal transcriptomes). When we got the first results we were quite surprised: more than 30% of the maternally-expressed genes were differentially expressed in the two morphs, and around 6600 different loci were de-regulated!
Figure 2.- Schematic diagram of Astyanax mexicanus embryonic development (top). From left to right: 2 cell stage, onset of gastrulation, mid-gastrulation, tailbud, somitogenesis, hatched larvae. Comparative analyses during Astyanax mexicanus embryogenesis (bottom). From left to right: volcano plot showing the distribution of differentially expressed genes relative to cavefish, downregulated in blue, upregulated in red (first panel), expression of dkk1b during gastrulation (second panel), expression of dkk1b at the end of gastrulation and somitogenesis (third panel), expression of hcrt in the hypothalamus at 24hpf and pax2a in the optic fissure at 48hpf (fourth panel, top and bottom respectively).
Then of course we wanted to test the maternal contribution to the cavefish phenotypic evolution. One of the greatest advantages of Astyanax mexicanus as a model is the interfertility between the different populations. In fact, in nature there are some geographic spots where hybridization of cave and river populations occurs nowadays. This unique feature allowed us to test the maternal contribution to a given phenotype by comparing F1 hybrids obtained by reciprocal crosses (hybrids obtained from surface fish eggs versus hybrids obtained from cavefish eggs). If the phenotype under study in the hybrids resembles the phenotype of the female morphotype, then we can say that there is a maternal effect on that trait. The results obtained here were also striking. We found that the patterns of gene expression in hybrids up to the end of gastrulation were exactly the same as those of their maternal morph. These results show first, that the morphotype-specific pattern of gastrulation is determined by maternal factors, and second, that maternal determinants influence embryonic development until stages much later than the maternal-to-zygotic transition.
After gastrulation, as development continues, all phenotypes analyzed became progressively similar between the reciprocal hybrids, and intermediate between the two pure eco-morphotypes. However, some of these morphotype-specific phenotypes at larval stages (hypothalamic patterning and eye regionalization) showed clear differences in the reciprocal hybrids, with a tendency towards the maternal morphs. This indicates that, when the zygotic genome (in a hybrid condition) takes over the control of development, it tends to homogenize the phenotypes, making less clear the full maternal effect observed at earlier stages.
Figure 3.- Schematic diagram of the crosses performed to test the maternal effect (first row). Expression of dkk1b at 50% epiboly (second row), expression of notail at 70% epiboly (third row) and expression of pax2a at 48hpf (fourth row).
Our work provided clear evidence that changes in the composition of the oocytes can modify the developmental trajectories, thereby contributing to phenotypic evolution. In this sense, the maternal transcriptome could react under specific environmental conditions, modifying subsequent interdependent developmental events, leading finally to a particular phenotypic outcome, in a way similar to a domino effect.
This work offers a new field for us to dig in. There are some questions we started to ask ourselves, for example could maternal genes be under selective pressure? Which mechanisms could account for their regulation within the ovary? How different is the maternal-to-zygotic transition in Astyanax morphs?
Research done by Jorge Torres-Paz, Julien Leclercq and Sylvie Rétaux at the Paris-Saclay Institute of Neuroscience, CNRS UMR9197, Université Paris-Sud, Université Paris-Saclay, France.
Due to the Coronavirus, Translational Immunology and the satellite BIS meeting were postponed from 26-27 March 2020 to the end of the year. We are happy to confirm the new date: 8-9 December 2020.
The aim of this conference is to bridge the translational gap in immunopathology, bringing together clinicians, research scientists and industry partners to discuss prominent advances from the bench to the clinicimmune The different sessions will have a particular focus on precision medicine in general, starting from disease-oriented cases and lessons learned. Innovative and alternative therapeutic strategies in immune-mediated disorders will be presented, besides the regulatory challenges that companies and researchers are dealing with.
Deadlines:
Abstract submission: 5 October 2020
Early Bird deadline: 27 October 2020
Late Registration deadline: 24 November 2020
Speakers:
Rosa Bacchetta- Stanford Medicine, US
Dirk Elewaut- VIB-UGent Center for Inflammation Research, BE
Alain Fischer – Assistance publique – Hôpitaux de Paris, FR
Martin Guilliams – VIB-UGent Center for Inflammation Research, BE
Pleun Hombrink – Sanquin, NL
Bengt Hoepken – Clinical Program Director, UCB Pharma, DE
Isabelle Huys – KU Leuven, BE
Christophe Lahorte – National Innovation Office & Scientific-Technical Advice Unit – (Famhp), BE
Bart Lambrecht – VIB-UGent Center for Inflammation Research, BE
Antonio Lanzavecchia – Institute for Research in Biomedicine, CH
Sophie Lucas – de Duve Institute, UCLouvain, BE
Bénédicte Machiels – FARAH Center, ULiège, BE
Melanie Matheu – CEO, Founder at Prellis Biologics, Inc., US
Massimiliano Mazzone – VIB-KU Leuven Center for Cancer Biology, BE
Kathy McCoy – University of Calgary, CA
Eoin McKinney – University of Cambridge, UK
Fiona Powrie – Kennedy Institute of Rheumatology, University of Oxford, UK
Federica Sallusto – Institute for Research in Biomedicine, CH
Georg Schett – Friedrich-Alexander University Erlangen-Nürnberg, DE
Marvin van Luijn – Erasmus MC, University Medical Center Rotterdam MS Center ErasMS, NL
Suzanne Eaton, Professor at the Technical University Dresden and Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, tragically died on 2 July 2019. Suzanne was a remarkable person, both as a scientist and as a human being. Having worked closely with Suzanne for many years, I remember here some of her key scientific contributions.
Suzanne truly loved science and was driven by a deep curiosity for nature. She was an exceptional scientist with a taste for profound and fundamental problems in biology, and she embraced novel, original and interdisciplinary approaches. Indeed, Suzanne was a pioneer in quantitative approaches to tissue morphogenesis and a leader in the field, bridging scales from cell biology to tissue dynamics. With her fast wit and broad knowledge, she inspired colleagues, co-workers and students alike. Working with her was always a joyful experience, playful and deeply enlightening. Suzanne was also a sophisticated piano player and she had a black belt in Taekwondo. As one of Suzanne’s close collaborators over the past 15 years, it has been a true privilege for me to have interacted with her on a number of exciting problems and to have had weekly joint group meetings with a broad and interdisciplinary spirit.
Born in Oakland, California, Suzanne did her PhD at UCLA in the group of Kathryn Calame. During her PhD, Suzanne worked on the transcriptional regulation of immunoglobulin heavy chain genes (Eaton and Calame, 1987). She then moved to the lab of Tom Kornberg at UCSF, where she worked on the fruit fly Drosophila melanogaster and began to investigate fundamental aspects of Hedgehog signalling. Suzanne discovered that Hedgehog is a membrane-associated signalling molecule and that its expression is confined to posterior compartment cells (Tabata et al., 1992). In 1993, Suzanne moved to EMBL in Heidelberg to the lab of Kai Simons. There, she investigated planar cell polarity in epithelial tissues and revealed how Rho family GTPases play a role in polarizing the actin cytoskeleton and regulating cell shape changes in the fly wing epithelium (Eaton et al., 1995).
In 2000, Suzanne moved to Dresden to help set up the newly founded Max Planck Institute of Molecular Cell Biology and Genetics. In this environment, her research flourished as she became a leader in a new field that brought together cell and developmental biology. She was curious about how morphogens such as Hedgehog and Wnt/Wingless that spread in a tissue over distances could be found tightly associated with membranes. She discovered that these morphogens travel while associated with membranous particles, which move between cells and act as vehicles for morphogen transport (Greco et al., 2001). She further established that these membranous particles are lipoprotein particles (Panáková et al. 2005).
Suzanne then became fascinated by the geometry of cell packing, which appears to be random but at the same time exhibits different types of order and structural features. She thus investigated the mechanisms that govern cell neighbour numbers and the establishment of hexagonal packing in epithelia, revealing a role for planar cell polarity proteins in this process (Classen et al., 2005). This interest in cell packing geometries and cell polarity patterns triggered stimulating discussions about the role of forces and cell mechanics in morphogenesis, which in turn brought about a fruitful, long-lasting and inspiring collaboration between our research groups. A first step in this collaboration was the development of vertex models that capture the forces that define cell shapes. By comparing experiment and theory, key parameters that characterize biophysical properties of cells could be inferred and a general mechanism for the emergence of hexagonal cell packing was identified (Farhadifar et al., 2007). Live imaging over extended periods of time then permitted Suzanne to quantify cell movements, cell flow patterns and dynamic patterns of planar cell polarity over time during Drosophila pupal development. These observations revealed that planar cell polarity patterns in the tissue are reoriented by cell flow and tissue shear. This provided new insights into the role of cell flow in shaping patterns during morphogenesis (Aigouy et al., 2010). Looking at cell polarity patterns at early and late time points in the wing imaginal disc revealed how planar cell polarity patterns that are aligned over large distances could emerge in a tissue. At early time points, cell polarity is oriented in random directions. Groups of cells then locally align their polarity with the help of signals at compartment boundaries, while the tissue is still small. This aligned pattern is then extended over larger scales by tissue growth (Sagner et al., 2012).
Another key question that Suzanne addressed is how the fly wing takes on its final shape. Interestingly, mutants of the protein Dumpy, which links the tissue to the extracellular matrix, exhibit strongly misformed wings. Live imaging of wing development in dumpy mutants revealed that mechanical attachments at the tissue margin have a direct and strong influence on final tissue shape. It was shown that the wing is shaped inside the pupa by an active mechanical process that involves tissue contraction and tissue flow, which depend on patterns of mechanical boundary attachments (Etournay et al., 2015).
Suzanne’s discovery that signalling molecules such as Hedgehog are transported over distances by lipoprotein particles, which are also carriers of lipids, led her to bridge the field of morphogenesis with that of metabolism. She therefore started a research programme to investigate metabolic regulation and the complex interplay between metabolism, growth and development. She discovered that Drosophila lipoproteins generated in the fat body (a structure playing a role similar to that of the liver) provide signals about the nutritional status of the organism that are sent to the brain where they accumulate. In the brain, in turn, insulin-like peptides are secreted to regulate insulin signalling. Surprisingly, lipoproteins accumulate in the brain if the fly is on a yeast diet but not when it is on a plant-based diet. In this case, flies develop and grow more slowly, and live longer, as a consequence of different insulin signalling despite the calorimetric food content being the same. This work thus provided fascinating insights into the regulation of metabolism under varying diets (Brankatschk et al., 2014).
What could be the adaptive roles of different diets? In a very beautiful paper, Suzanne and her team investigated the effects of plant food compared with yeast food on the survival of Drosophila larvae and adults at different temperatures (Brankatschk et al., 2018). They showed that whereas flies growing in warm temperatures prefer yeast food, they prefer plant food when they are maintained at cold temperatures. Furthermore, flies on a plant diet can survive cold temperatures at which flies that are kept on a yeast diet will die. Thus, the choice of the appropriate food is important for survival during winter periods in temperate climates. A key difference between plant and yeast food is the ability of plants to produce polyunsaturated fatty acids. Suzanne and colleagues showed that the difference in diet leads to different lipid composition of membranes. Membranes of larvae on a plant diet maintain fluid properties and exhibit disordered membrane organization at lower temperatures, suggesting that these membrane biophysical properties are modulated by nutrition and are important for survival in the cold.
Remembering her contributions reveals the immense breadth of Suzanne’s work and her ability to bridge different fields and disciplines when addressing important questions in biology. Her work is characterized by very original and deep studies using strong quantitative approaches. She always looked at fundamental problems from new angles and thus made important and surprising discoveries. Her loss leaves a gaping void, and her sharp intellect and warm personality are missed tremendously.
The Blythe Lab at Northwestern University seeks to recruit a motivated postdoctoral fellow to investigate chromatin dynamics in early Drosophila embryogenesis.
Research in the Blythe Lab focuses on a critical period of embryogenesis termed the maternal-to-zygotic transition (MZT). During this time, embryos establish an initial ‘ground state’ of chromatin structure that defines the initial cis-regulatory landscape underlying the embryo’s first cell fate decisions. We are interested both in how the initial state is established and how this constrains the interpretation of developmental cues during pattern formation. To study this question, we apply a combination of genetic, genomic, and quantitative imaging approaches to understand the mechanisms that shape the embryonic chromatin landscape.
Projects are available in three major areas at the interface of developmental biology, epigenetics, and systems biology: 1) Temporal control of zygotic genome activation; 2) Patterning-dependent chromatin remodeling and gene regulatory network function; 3) Conflicts between DNA replication and transcription.
We are particularly interested in candidates with experience in genomic approaches (RNA-, ChIP-, or ATAC-seq), analysis of genomic data, quantitative confocal microscopy, biophysical approaches, and/or Drosophila genetics. The position available immediately.
We have two fully funded PhD positions in the Wheeler lab at University of East Anglia, Norwich, UK.
NEUcrest is an Innovative Training Network (ITN) project, funded by the European Union Horizon 2020 Programme. The neural crest (NC) is an essential stem cell population of the vertebrate embryos that gives rise to various tissues in the body such as the cranial facial cartilage, peripheral nervous system and the Adrenal Medulla. NEUcrest focuses on integrating academic, clinical and industrial research for a better understanding of neural crest development and neural crest related diseases called Neurocristopathies. These pathologies are a major group of congenital diseases in human, and a heavy societal concern. The NEUcrest network comprises 20 partners in academia, industry and hospitals from seven European countries, gathered in a synergistic effort to advance knowledge and outreach about these diseases.
Modelling Neurocristopathies in Xenopus, mechanisms and drug screening
Micro RNA regulation of neural crest development
Please follow these links for more information:
https://euraxess.ec.europa.eu/jobs/447869
https://www.euraxess.fo/jobs/461086
Or contact Dr. Grant Wheeler for more information: Grant.Wheeler@uea.ac.uk
In this episode we’re bringing you highlights from the Society’s Centenary Conference, held up in Edinburgh last month.
We’ve got stories of sneaky sheep, substandard racing stallions, the Vikings of the Scottish Isles and a ceilidh with a scientific spin. Plus, news from the front lines of the sperm wars.
If you enjoy the show, please do rate and review and spread the word. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip
In this episode from our centenary series exploring 100 ideas in genetics, we’re uprooting the tree of life – asking whether we should believe our eyes or our sequencing machines when it comes to deciding what makes a species.
Plus, the greatest comebacks of all time – we look at the science of de-extinction and find out whether Jurassic Park could ever become a reality.
If you enjoy the show, please do rate and review and spread the word. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip
Two weeks ago, we had the opportunity to attend the Company of Biologists Workshop, “Understanding Birth Defects in the Genomic Age”. This workshop brought together a diverse collection of basic developmental biologists, human geneticists and clinicians to discuss the current challenges and opportunities in the field of birth defects research. We can almost guarantee you that none of the groups of attendees would normally overlap at any other meeting. And yet, what quickly became apparent was that there was so much in common between everyone in attendance.
The setting for the meeting was stunning. Set at Wiston House in the English countryside not too far from Brighton, history oozed from every corner of the building. From the delicious catering, to the beautiful (but rainy) countryside walk, to the very interesting talk on the history of the house, this venue provided an epic background for what would be an extremely stimulating three and a half days.
The meeting was unique right from the start. It was definitely the smallest meeting we had ever attended. There were only about 33 people total, and we each had the opportunity to introduce ourselves to the group on the first day. We were asked to give a few slides introducing ourselves as well as a “problem” (a topic that we would like help with) and “solution” (something that we were good at/could use to help others). Right away this encouraged discussion and it became quickly apparent how each of our skillsets would be able to help not just each others’ research, but contribute a unique perspective to the group.
Participants at the Workshop
In addition to traditional scientific talks, we had the opportunity to sit down and talk amongst the group about some of the issues which we would like to address. Collectively, birth defects are the number one cause of infant mortality in the USA, but it is sometimes challenging to justify studying individual rare developmental defects. Many of our discussions centred around how to increase public awareness of our research and to emphasize the huge impact of return of results to families – even if a genetic diagnosis doesn’t lead to a treatment, patients and families can be hugely comforted to know more about the underlying cause. John Wallingford gave a stirring talk about the disturbing history of society’s (including the medical profession’s) poor treatment of individuals with congenital anomalies. There was unanimous agreement amongst the group that we needed a new term for birth defects that was both more sensitive and more inclusive. There was much discussion, but the group was not able to come to a consensus as to a better term moving forward. One of our favourite suggestions was that perhaps we needed to create a new word entirely!
One of the goals of the workshop was to generate actual concrete steps to address the above issues. Working groups were established to draft a white paper, review articles, social media campaigns, and other methods to increase the awareness of this very important field of research. One of they key action items became bringing together a similar group of people again to build on the ideas started at this workshop. The Company of Biologists is already planning a meeting on developmental disorders for 2021; hopefully this will provide another opportunity for a meeting of minds to continue to forward the cause.
As two early career researchers funded by the Company of Biologists to attend the workshop, we gained great insight into the diverse approaches being used to study birth defects research. In addition, it provided a unique opportunity to discuss and learn about larger scope projects such as impacting public awareness and advocating for increased funding for a particular area of research.
At the conclusion of the meeting everyone left inspired and ready to act. We are looking forward to 2021!
Find out more about The Company of Biologists’ Workshops, including our 2020 schedule and details of how to apply for funded places, here:
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