We are seeking a highly motivated, organized and enthusiastic postdoctoral fellow or research associate to study embryonic kidney development and its relationship to developmental kidney diseases. We are interested in the role of Wnt signaling in shaping nephric tubules, utilizing Xenopus (frog) embryos and mammalian tissue culture as models. Current goals include: 1) Determining how junctions are formed during tubule formation; 2) Modeling how patient mutations result in human developmental kidney diseases; 3) Discovering novel components affecting nephron development; 4) Visualizing in vivo tube formation using advanced live imaging techniques; 5) Generating transgenic animals to visualize nephrogenesis in vivo
Current projects utilize developmental, molecular and cell biological approaches including imaging in living embryos. Applicants with a Ph.D., M.D. or equivalent and a strong background in Developmental Biology, Embryology, Cell Biology, Molecular Biology and/or Stem Cell Biology are highly encouraged to apply. Salary and benefits are commensurate with relevant experience. Review of applications will continue until the position has been filled.
Please send your CV, cover letter indicating current and future research interests, and the name/email address of three references to:
Registration is now open for our virtual networking event!
With COVID-19 cancelling conferences, researchers have lost one of their best ways to network. So we thought we’d try to help, aided by software that creates a virtual space for researchers to interact via video.
At this event you’ll meet other developmental biologists from across the world, discuss relevant topics and test your knowledge with a pub quiz.
The event will be split into four parts:
Speed networking – meet the other attendants
Discussion tables – topics picked by attendees, currently ranging from publishing to careers, starting your lab to promoting diversity (we welcome further suggestions and are looking for table chairs to lead the discussions – just email thenode@biologists.com)
Pub quiz – how good is your devbio knowledge? Winning table gets a real life prize. Bring your own beer or coffee
Informal hang out – once the structured sessions are over, we’ll leave the session open for people to hang out
An ERC funded research engineer position in Developmental and Cell Biology is available at the IBDM in Marseille in the group of Frank Schnorrer. The appointment will be for one year with a possible extension for up to four years.
We are looking for a highly motivated scientist, with experience in working at an English-speaking international research institute. The research project will require a particular knowledge of imaging, image processing, genetics and experience in developmental and cell biology in general.
The Schnorrer group is located at the Institute of Developmental Biology of Marseille (IBDM), an interdisciplinary research center with a strong focus on quantitative in vivo biology, microscopy and biophysics. Our group is specifically interested in how the contractile elements of muscles called sarcomeres are built during development and how they are maintained during the life of the fly.
The Tata lab in the Department of Cell Biology, Duke University School of Medicine has two openings for postdoctoral researchers to study cellular plasticity mechanisms in lung injury repair and tumorigenesis. We seek to understand the genetic and epigenetic basis of organ regeneration and tumorigenesis. We study the properties of stem/progenitor cells in diverse epithelial tissues (with a primary focus on lung) and their relationships with neighboring tissues in pathophysiological conditions. We utilize in vivo mouse genetics, live imaging, 3D organoids, genome-wide Cas9/Crispr based functional genetic screening, and next generation sequencing technologies to study the behavior of tissues at single cell level. We offer an inspiring intellectual, collaborative and multidisciplinary research environment to support your career goals and provide access to state-of-the-art facilities. Candidates with background knowledge and hands-on experience in transcriptional regulation, 3D-organoids and bioinformatics skills are particularly welcome.
Requirements
– A PhD or MD/PhD (or equivalent) in biological sciences (cell & developmental biology or a related field).
– Strong research background in transcriptional regulation, cell biology, molecular biology, mouse models of cancer, and/or biochemistry. Prior experience in stem cells, Cas9/Crispr gene editing, 3D-organoid cultures, chromatin biology and bioinformatics is advantageous.
– Evidence of successful completion of a research project (publications)
– Ability to work independently; interpret, present and discuss experimental data
– Excellent communications skills
My mentor, Bruce Appel, emphasizes the importance of communicating science clearly and precisely. Consequently, I have watched my peers and myself deliver ever-improving talks, posters, and manuscripts during our time in the lab. I think that many people in science appreciate that clear communication is essential for others to be able to interpret findings and effectively build upon what has been done. A corollary lesson that I wasn’t expecting to learn from our latest project, published recently in Nature Neuroscience (Hughes and Appel, 2020), is how imprecise language can muddle and confound understanding, obstructing progress.
Our lab studies oligodendrocyte lineage cells using zebrafish as a model system. In the central nervous system, oligodendrocytes wrap neuronal axons with myelin, a lipid-rich membrane that increases conduction velocity. Zebrafish are both genetically and optically accessible, allowing us to image cellular interactions during myelination in live larvae. A live-imaging experiment can catch oligodendrocytes extending numerous, arborizing processes that search for and begin to wrap axons with myelin membrane. Some of these nascent wraps continue to grow and mature, whereas other wraps appear to be eliminated. How are myelin sheaths eliminated?
Many structures that also are studied by live-imaging, like neuronal neurites, undergo similar deformations during development. Neurons elaborate and occasionally withdraw neurites, and this latter process is termed “retraction”. Oligodendrocytes generate processes that branch similarly to neurites. Like neurites, these processes withdraw, and these events have been described as “retraction”. But oligodendrocyte processes also do something very different than neurites: upon contacting a target axon, an oligodendrocyte process can deposit a reservoir of myelin lipids that spreads like a liquid droplet as the process begins wrapping the axon (Nawaz et al., 2015). Can fluid-like myelin sheaths, like the simple processes that gave rise to them, also be withdrawn? Live confocal microscopy doesn’t show us sheaths unraveling or processes reeled in by the cell body. Instead, sheaths merely reduce in size and disappear. By using the word “retraction” to describe all oligodendrocyte process disappearances, an untested mechanism was invoked to account for all myelin sheath elimination.
If myelin sheaths aren’t retracted, what alternative mechanisms could remove sheaths? Many structures in the developing nervous system, including synapses, neuronal precursors, and neurons, are overproduced and can be pruned by microglia, the resident immune cell type of the CNS. We had previously found a number of similarities between the formation of myelin sheaths and neuronal postsynapses (Hughes and Appel, 2019), raising the possibility that these structures might also be eliminated similarly.
Admittedly, I spent a lot of time thinking about microglia before they constituted a reasonable suspect in sheath elimination. Early in grad school, I had read a paper that found that microglia regularly survey the zebrafish spinal cord and quickly swoop in to clear laser-ablated neurons (Morsch et al., 2015) and I was really curious to see if these cells interact with oligodendrocytes during normal development. Something I particularly like about working with zebrafish is how easy it is to casually pursue these types of side-curiosities. I lost no time to generating the construct to label microglia, because I did it in parallel with other cloning I needed to do; I injected the construct to generate a microglia reporter transgenic line after I had performed my priority injections for experiments that week. A few months later, I had a microglia reporter line and was ready to find out if microglia and oligodendrocytes interact during myelination.
A microglia (yellow) engulfing nascent myelin sheaths (magenta) in the spinal cord of a zebrafish. Scale bar, 10 um.
The first time I timelapse imaged microglia interacting with myelin, to my surprise and delight I found microglia engulfing nascent myelin sheaths. I presented a video at lab meeting and was encouraged by the enthusiasm and questions raised by my labmates. How many microglia are there and how many sheaths are they eating? Do oligodendrocytes die when their sheaths are eaten? What regulates sheath phagocytosis? These tractable questions started to crystallize the phenomenon into a project.
At this stage, our recognition that myelin sheath development shares numerous similarities with synapse development was pivotal. Work by Dorothy Schafer, Beth Stevens, and Marie-Ève Tremblay had previously shown that microglia contact and phagocytose synapses in a neuronal activity-regulated manner (Schafer et al., 2012; Tremblay et al., 2010). Inspired by this work, the hypothesis and predictions that would form the foundation of the project emerged by analogy. Like synapses, do microglia phagocytose myelin in an activity-regulated manner? Will preventing pruning cause extra myelin to persist? With a path laid out, experiments moved swiftly. We found that microglia do survey and phagocytose myelin sheaths, and neuronal activity spurs microglia to trade-off between interacting with neuronal somas and phagocytosing myelin from myelinated axons. We further found that this program is robust enough that blocking it (via microglial ablation) caused excessive and ectopic myelin to develop.
We wrote up and submitted a much shorter version of our paper, concurrent with deposition to the preprint server BioRxiv, in summer 2019. In review, it became clear that microglia-mediated myelin pruning was incompatible with our field’s understanding that sheaths are solely eliminated by retraction. At first, I saw this as a purely semantic problem: myelin sheaths disappear, and the word “retract” has been used to describe this observation but oversteps into a mechanism that hasn’t been tested. I was resistant to confronting retraction but was persuaded by a reviewer’s argument that it would be informative to know what fraction of sheath elimination is contributed by microglia. Figuring out how to quantify sheath loss in an unbiased way took longer than any other experiment in the paper and pushed my image analysis forward in new ways. These data were the very last addition to the paper, but they appear inconspicuously in the middle of Figure 2! Ultimately, we found that sheaths are both phagocytosed by microglia and disappear independently of microglial contact, with phagocytosis accounting for the majority of sheath loss. This latter, microglia-independent category of lost sheaths might be called “retraction”, as we do in the paper.
How many sheaths are eliminated by microglia? Method to detect changes in myelin over time (cyan) allowed us to determine how many disappearing sheaths are engulfed vs disappear without microglia contact (“retract”). Arrowhead marks an engulfed sheath; open arrowheads mark engulfed myelin shuffling within microglia. Scale bar, 10 um.
I still have some reservations about “retraction”. Prior to labeling microglia, we accepted that sheaths were solely eliminated by retraction: when oligodendrocytes were the only cell type visible, it was easy to grant cell autonomy to all visible changes and to forget that other cell types are lurking in the dark. Similarly, it’s possible that additional unlabeled cell types might engulf the microglia-independent subset of disappearing sheaths.
References
Hughes, A. N. and Appel, B. (2019). Oligodendrocytes express synaptic proteins that modulate myelin sheath formation. Nat. Commun.10, 4125.
Hughes, A. N. and Appel, B. (2020). Microglia phagocytose myelin sheaths to modify developmental myelination. Nat. Neurosci. in press.
Morsch, M., Radford, R., Lee, A., Don, E. K., Badrock, A. P., Hall, T. E., Cole, N. J. and Chung, R. (2015). In vivo characterization of microglial engulfment of dying neurons in the zebrafish spinal cord. Front. Cell. Neurosci.9, 321.
Nawaz, S., Sánchez, P., Schmitt, S., Snaidero, N., Mitkovski, M., Velte, C., Brückner, B. R., Alexopoulos, I., Czopka, T., Jung, S. Y., et al. (2015). Actin Filament Turnover Drives Leading Edge Growth during Myelin Sheath Formation in the Central Nervous System. Dev. Cell34, 139–151.
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A. and Stevens, B. (2012). Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner. Neuron74, 691–705.
Tremblay, M.-È., Lowery, R. L. and Majewska, A. K. (2010). Microglial Interactions with Synapses Are Modulated by Visual Experience. PLoS Biol.8, e1000527.
The University of Lyon is a worldwide academic site of excellence. Labelled IDEX in 2017, it is located in the heart of the Auvergne-Rhône-Alpes region, in the Lyon Saint-Étienne basin. Structured around 12 members, the University of Lyon has three major ambitions:
· To design a large, attractive, responsible university with a reputation for excellence and innovation and a strong international reputation;
· Propose a training and research program of excellence, in line with the expectations and changes in society;
· Develop and enhance the dynamics of the Lyon Saint-Étienne site, in conjunction with all the players in the area: citizens, associations, businesses, local authorities (Lyon and Saint-Étienne metropolitan areas, Auvergne-Rhône-Alpes Region, other local authorities).
The University of Lyon is looking for a research engineer (IR) in bioinformatics for the LabEx CORTEX. The LabEx CORTEX brings together 22 research teams in Neuroscience who conduct multiscale research, from molecular and cellular bases of neuronal physiology to cognitive functions in normal and pathological contexts. It is an exciting international multidisciplinary research environment. The LabEx activities are divided according to three axes: research, education and dissemination.
JOB DESCRIPTION
A full-time position is available for a period of 2 years (renewable) to establish a bioinformatics platform within the LabEx CORTEX of the University of Lyon.
We are seeking highly motivated candidates with a PhD in biological sciences (ideally in Neurosciences) and strong experience in Bioinformatics, in particular with next generation single cell RNA-Sequencing analysis. The candidate will have a published track record within this field and strong knowledge of up to date bioinformatics tools. She/he will have good communication skills in French and English, strong capacity to develop networks (e.g. a previous experience in managing a platform or a common facility). Finally, the candidate will have the task of developing/establishing new protocols and teaching/sharing them to the CORTEX community.
The selected candidate will work closely with local genomic facilities in order to lay the foundation of a bioinformatics platform to assist LabEx CORTEX teams in performing single cell RNA-Sequencing experiments. Hence, she/he will be involved in:
Facilitating the planning of new single cell RNA-Sequencing experiments.
Assisting teams in the analysis of currently available datasets, either directly or by the training/supervision of students/staffs from the participating teams.
Establishing new techniques or procedures of general interest, e.g. establishment and comparison of adult CNS tissue dissociation protocols… gradually evolving to integrate complementary datasets (e.g. Chip-Seq, Slice-Seq)
PROFILE
Competences:
– PhD in biology/neurosciences
– Expertise in bioinformatics analysis
– Advanced expertise in data collection, processing and analysis
– Good knowledge of programming languages (R, Python…)
– Technical English
– Teaching and knowledge transfer competences
– Build and manage databases
Soft skills:
– Excellent communication skills
– Proactive, autonomous and versatile
– Strong ability to work in a team
APPLICATION
Send resume, reference (name, email, address, phone) and application letter to jennifer.beneyton@inserm.fr
A postdoc position is available within the Conduit lab at the Institut Jacques Monod in Paris. See job advert attached and get in touch if you’re interested in studying microtubule nucleation in Drosophila (paul.conduit@ijm.fr).
In this episode, Kat Arney takes a look at the world of epigenetics to find out if more than DNA passes on to the next generation, whether Darwin was wrong and Lamarck was right, and how to pimp your genome. Plus, we meet the Mickey Mouse Mice – a strange (but cute!) example of transgenerational epigenetic inheritance.
If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip
Happy to share the latest manuscript by André Castro @castro_neuro from the @HCuntz with @GTavosanis labs! We show how a temporal arrangement of stochastic developmental processes achieves efficient dendritic trees both in terms of wire and function. #Drosophila#comp_neuro
One PhD student and one postdoc position will be available in the @GTavosanis lab starting from September 2020.
The two planned projects will focus on:
The cellular mechanisms that support the differentiation of neuronal dendrites (see Stuerner et al., Development 2019). This project will combine the generation of molecular tools for acute manipulation of protein activity with high-resolution in vivo microscopy. We will closely cooperate with neuronal morphology modelling groups.
The circuit mechanisms that support the consolidation of memories in the adult fly brain. Combining detailed anatomical insight and refined genetic tools to manipulate identified neurons, you will investigate how experience and learning modify a circuit’s output. This project is embedded within the frame of the DFG-funded Research Unit FOR 2705 that includes highly interactive groups with complementary expertise (https://www.uni-goettingen.de/en/601524.html ).
All infos and application: https://jobs.dzne.de/en/jobs/50580/phd-student-fmd-and-postdoc-fmd-182520206-182620206
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In this episode, Kat Arney takes a look at the world of epigenetics to find out if more than DNA passes on to the next generation, whether Darwin was wrong and Lamarck was right, and how to pimp your genome. Plus, we meet the Mickey Mouse Mice – a strange (but cute!) example of transgenerational epigenetic inheritance.