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Two PhD positions in Regulatory Evolution, Tschopp group, University of Basel, Switzerland

Posted by , on 1 August 2016

Closing Date: 15 March 2021

The Laboratory of Regulatory Evolution (Tschopp group) at the Zoological Institute, University of Basel, is hiring for two fully funded PhD positions.

Our research interests focus on two main questions: 1. How is phenotypic diversity generated during vertebrate embryogenesis? And 2. how can developmental processes be modified to drive morphological evolution? We are particularly interested in investigating how the evolution of gene regulation is underlying these phenomena. As a model system, we are studying the development of the vertebrate skeleton with its associated neuromuscular system.

In a first project, we will investigate the gene regulatory networks underlying the generation of skeletal cell types, originating from distinct embryonic sources and in different species. This will allow us to assess the developmental and evolutionary constraints on gene regulation during cell type specification. Secondly, we are interested how cell specification and embryonic patterning are intertwined. To this end, we will study the specification of synovial joints during the embryonic outgrowth of digits, a process contributing important aspects of the patterning diversity seen in the hands and feet of vertebrates.
Both projects build on solid foundations of confirmed preliminary data. For more information please visit http://evolution.unibas.ch/tschopp/research/index.htm

We will address these questions using a range of experimental methods, including embryology in chicken, mice and fish; functional genomics (RNA-seq, ChIP-seq, ATAC-seq, STARR-seq); cell culture and viral gene delivery; genome editing (CRISPR-Cas9); bioinformatics and in silico modeling.

Successful candidates will have a background in molecular and/or developmental biology, and ideally will have a basic understanding of Unix and the R language for statistical computing.

Please send your application with a brief statement of motivation, a current CV and contact(s) for references (where applicable) to patrick.tschopp@unibas.ch
Evaluation will begin on Sept. 1st 2016 and suitable candidates will be contacted shortly after.

The University of Basel is an equal opportunity employer and encourages applications from female candidates.

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MBL Embryology Course 2016

Posted by , on 1 August 2016

“My dear, here we must run as fast as we can, just to stay in place.

And if you wish to go anywhere you must run twice as fast as that.”
L. Carroll ‘Alice Through the Looking Glass’

 

We write this while we finish the last experiments for the final Show n’ Tell on Saturday full of reluctance to finish this course. Samples fly all over the lab; solutions are changed and something blue boils somewhere in the room.

Looking back, six weeks ago we had an approximate idea of what the MBL Embryology Course was about: people doing science 24/7, lectures and a lot of organisms with names you can barely pronounce. What we did not know is that the experience was all of that and more.

The first day was weird. People hanging their posters on the walls, rushing to get ready to tell other people about what is basically their life in the lab. After a while, everybody was talking with each other about science and how much they want to try new things. Our excitement grew as we realized that we would not only get to experience a plethora of organisms, but we would also learn from peers who are expert at widely diverged backgrounds. Little did we know about what we were really in for, though!

After that, the routine was as follows:

You wake up, rush to stuff yourself with breakfast, get a coffee and run to the Speck Auditorium to hear about the nuts and bolts of a new organism. From sea urchins to worms (flat or not), through articulated arthropods, squishy jellyfish and ctenophores, hemichordates, urochordates, glowing zebrafish or little mice, we learned about how they develop. One of the first things you realize is the kind of amazing things people are doing on this crazy endeavor of understanding how life works. All organisms share common features and are different from each other, highlighting how important all of them are. The second thing you realize is how passionate people are about their work, and you cannot help but remember why you became a scientist on the first place.

After the lectures we had what’s been called The Sweat Box for many years. This consists on a freestyle Q&A session about the contents of the lecture that usually would diverge on questions about anything related to the subject. During this time, we had the opportunity to discover how much people know about their (and other) organisms, and how they have contributed to their field and biology in general. As the course went on, our confidence grew to ask seemingly the strangest and deepest of questions. These turned out to be questions of broad interest or potential projects, which may highlight the key points of developmental research for the next decade.

After lunch, we had laboratory until the (usually very, very late) evening. The laboratories consisted on a brief introduction to the organism and the available tools. Then, it was up to you which type of question you wanted to ask: Big or small, simple or complex, you were given complete freedom and the TAs and PIs would usually challenge us to try new and classic experiments. You didn’t need to have any hypothesis or rigorous experimental design, as there should be no limitation for your curiosity. You just followed your intuition to give it a try for anything jumping up from your mind. It was a great chance to examine your crazy ideas, which your advisor might not allow you to test at your home laboratory, applying new available technologies to try experiments that were not previously feasible. Looking back, this curiosity-driven science is what we think that makes being a scientist an awesome job and we encourage everybody to do it, because that’s where magic happens. What would happen if you fuse two sea urchin embryos? Would a worm develop normally if you spin it down in the centrifuge? What is the smallest piece of an animal that would regenerate? Is that experiment mentioned earlier during the lecture really impossible? These questions are also important, and we had so much fun trying to answer them. Most of our experiments did not work, but science is about that, too: What basic principle have you learned by doing that experiment?

(It is important to mention that it is great seeing how the kind of experiments we the students propose still can surprise somebody that has been working in the field for many years. This is one of the great things about science: the capacity of being amazed)

Most importantly for our research in the ‘real world’, we had the opportunity to try new techniques and explore the use of tools we had never otherwise been able to use. For each established organism*, there are usually are some common experimental skills which are not utilized by researchers studying other organisms. We had the chance to learn many interdisciplinary, useful experimental skills and tool-making methods that can be applied to different organisms to broaden the possibility and feasibility of experimental designs in each module. Moreover, the training on different types of microscopes and imaging techniques enabled us to utilize appropriate methods, generating high-resolution images for different purposes and organisms. We could even separate overlapping spectra to distinguish (up to eight!!) different fluorescent markers on one sample for co-localization studies.

Every two weeks we got to present our data in the so-called Show n’ Tell. The recipe for it is a powerpoint presentation, a timer and people waiting to be amazed by the kind of data you collected in two weeks. During the time you were given, it was up to you presenting (or even dancing!) one, two or n experiments. It was very common seeing jaws dropping or people clapping, and everybody was smiling as they saw what a great time people had trying new experiments or collecting beautiful images. Our evening was spent laughing and embracing each other’s scientific creativity, an essential factor for the development of us as scientists.

Starting from first cell division, we had the opportunity to visualize the various types and patterns of cleavage processes among different organisms. We got to witness the beauty of biodiversity and how precisely it is regulated. When observing how a new life begins and grows, it is difficult to describe how deeply we were touched by the exquisiteness of life.

But not everything was about science! We had Sundays off, that we usually spent (not necessarily in this order) doing laundry, sleeping or exploring the beautiful towns of Woods Hole and Falmouth. We also had the opportunity of going Whale Watching, participating in the Independence Day costume parade and swimming in the bioluminescent ocean. During these six weeks of being awake at all hours, failing and succeeding together and enjoying our time off together, we became closer and closer to each other. With our virtues and defects, we have become friends.

Because science should be about that: whether your organism is big or small, squishy or hard, pigmented or transparent, we all are in the same boat. We all are trying to understand how life works, and we all should collaborate towards a better understanding of (in this case) embryology and development.

 

IMG_5198

 

We’d like to finish this little story thanking our Course Directors, Richard and Alejandro, who made all of this possible. We’d also like to thank all the Faculty and TAs that spent endless hours preparing all the experiments so we could have fun in the lab. We couldn’t have done any of this without our amazing Course Assistants Wes, Chris and Brittany, who took care of everything and are a fundamental part of the course. We also appreciate the endless support from outside of course: the specialists from Zeiss and Leica, teaching us how to generate amazing images, and other sponsor companies providing the latest-model equipment for us to perform fancy experiments. And last, but not least, we’d like to thank you reader, for being curious enough to read this little piece. Never stop being amazed and get out your comfort zone, and magic will happen.

 

Joaquín, Aleisha and Tsai-Ming
MBL Embryology Course, Class of 2016

 

 

Joaquín Navajas Acedo is a Grad Student from the Grad School of the Stowers Institute for Medical Research in Kansas City, Missouri (USA). He is currently working on the establishment of cell polarity using zebrafish at the Piotrowski Lab (http://research.stowers.org/piotrowskilab)

Aleisha Symon is a PhD student from Monash University in Melbourne (Australia). She is currently researching genes that are involved in the development of the mammalian testis at the Hudson Institute of Medical Research in the Harley lab (http://hudson.org.au/profile-prof-vincent-harley/)

Tsai-Ming Lu is a PhD student from Marine Genomics Unit at Okinawa Institute of Science and Technology (OIST) Graduate University, Okinawa, Japan. He is working on the genome project of dicyemid mesozoan, Dicyema japonicum, a parasite inhabiting in the renal sac of octopus, to understand the mechanisms of regressive evolution and adaptive radiation (https://groups.oist.jp/mgu)

 

PS: Some of us live-tweeted during the 6 weeks we spent at the MBL using the hashtag #embryo2016. If you want to get a good idea about what the course was like, please visit: https://twitter.com/search?q=%23embryo2016&src=typd

 

*The usage of the expression ‘model organism’ and ‘non-model organism’ was passionately discussed during one of the sessions in the Sweat Box. Since each organism can be a model, we decided that the term ‘canonical’ or ‘established’ would be more appropriate or not even adding a label. There is a recent article that discusses the matter (http://www.cell.com/current-biology/fulltext/S0960-9822(16)30604-2)

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July in preprints

Posted by , on 1 August 2016

Our latest monthly trawl for preprints. See June’s post for background, and let us know if we missed anything


This month we found preprints on various themes in developmental biology, as well as a lot of work that we hope will be of general interest to the community.

One of July’s most talked-about preprints tackled a subject felt keenly by most scientists, let alone developmental biologists: the journal impact factor. Vincent Lariviere, Stephen Curry and colleagues from Springer, AAAS, PloS, The Royal Society, eLife and EMBO presented an alternative method to generate citation distributions. July’s tranche also features zebrafish lamination and echinoderm regeneration, a hefty dose of evo-devo,  plenty of techniques and resources, and expanded genomes for humans, flies and mice.

The preprints listed below are hosted on biorxiv, arxiv and F1000Research.

Happy preprinting!

 

Developmental Biology & Related

 

Techniques

 

In Silico Modelling/Tools/Stats

 

Genomics

 

Publishing

 

 

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This month on the Node – July 2016

Posted by , on 1 August 2016

In case you missed it, here’s a round up of our July content, with lots of developmental biology research highlights (inc. microfluidics, zebrafinches and 3D retinas), as well as some art, some history, and some opinions. Happy reading!


Research

Christopher Demers wrote about microfluidic chambers and how they can be a useful tool for developmental biologists,  Carloine Dillard introduced her recent work using Drosophila neural stem cells as a model for understanding the developmental origins of tumours, and Aysu Uygur told us what chickens and zebrafinches tell us about how to pattern different-sized tissues.

 

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Avian development from Aysu’s piece

 

Marcos Simoes-Costa described how a fusion of classical and modern techniques helped to define and control the neural crest, Amelia Lane told the story of  differentiating photoreceptors from patient iPSCs and the great promise the technique has for retinal degeneration, and The DMDD wrote about how Zika has put birth defects in the spotlight.

 

Cranial neural crest cells of a chick embryo. Neural crest cells (purple/blue) can be seen migrating away from the central nervous system (red).
The neural crest from Marcos’ piece

 

Jingi Wu wrote about what ATAC-seq revealed about the chromatin landscape of the early embryo, and Wouter Masselink told us about a new cell type that orchestrates the development of the fin and sheds light on the fin-to limb transition.

 

AFIC infiltration into the AER controls fin fold induction. AFICs have a shared somitic origin with the muscle progenitor pool (green) and migrate into the AER (yellow). Upon infiltration into the AER, the AER folds onto itself and forms the AF (red). This infiltration event is absent in tetrapods such as mouse and chicken. AFICs have a dual role in inducing fin fold formation and secreting collagens needed for actinotrichia formation.
Wouter’s model for fins and limbs

 

Lab life

In our latest ‘Day in the Life’ series, Yoshimasa Hamada gave us an insight into what life is like in a cricket lab, Ngang Heok recounted his time in Singapore thanks to a Development travelling fellowship, and Rachna Narayanan wrote a report from the joint BSCB-BSDB Spring meeting in Warwick.

 

fig1
Crickets from Yoshimasa’s lab

 

History and Art

Máté Varga told the fascinating story of George Streisinger, Hungarian founding father of zebrafish research and social activist (really worth setting aside twenty minutes to read this!)

 

Streisinger
Geogre Streisinger

 

Mark Hintze (developmental biologist) and Diana Gradinaru (artist) introduced their wonderful animation about the questions of developmental biology. The piece really gives wonderful context to the video:

 

 

Brexit

Gary McDowellVicki Metzis and Wouter Picture4Masselink gave us three quite different takes on what Brexit means for them and for science. A month on, all we know is that the uncertainty surrounding the UK science’s future is not going to be short lived.

 

Publishing

We started a new feature: this month in preprints, which aimed to collate and promote the latest devbio & related work deposited in preprint servers in the last month. Look out for July’s selection later today.

 

Jobs

Over on our jobs page, we had postdocs come up in Florida and Cologne, and PhDs in Groningen and Charleroi Brussels.

 

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BSCB BSDB Joint Spring Meeting Report

Posted by , on 28 July 2016

The BSDB had its joint Spring Meeting with the BSCB earlier this year in April (10th -13th). It was my first time at the Meeting, which had been enthusiastically sold to me as “a good one, a fun one – they have a pub quiz!” and although I had been ‘sent to Coventry’, I have to confess, I had a great time. It was a busy 3 days, brimming over with interesting talks and stellar plenary and medal lectures. The concurrent sessions were on topics of interest for both cell and developmental biologists and so I ended up flitting between the talks of the concurrent sessions each day. Unfortunately, due to the impossibility of being in two places at once, there were excellent talks that I did miss and I apologise to these speakers for my non-attendance. I also want to say a big thank you to the speakers who have very kindly given me permission to write about the unpublished work they presented.

The meeting started, for me, with a Career Workshop on the Sunday afternoon. It was organised as a series of roundtable discussions with lecturers, group leaders, and people in industry, science publishing and communication. I got to speak to Paul Conduit, a Henry Dale Fellow at the University of Cambridge, Anne Wiblin from Abcam who provided the perspective of science life in industry, and Catarina Vicente from the Node, with whom I discussed the power of Twitter (and cakes) for communicating science.

Sunday evening’s plenary lectures were given by stalwarts – Mark Kirschner gave the BSDB Plenary Lecture and Ruth Lehmann the BSCB Plenary Lecture.

Mark Kirschner’s lecture sought to give quantitative answers to a fundamental question – “what is the economy of RNA and protein in embryonic development?’ with impressive technology and precision. By examining the dynamics of RNA and proteins on a single cell level, the Kirschner group has been able to show that while the correlation between the mRNA and protein levels is 0, the protein synthesis rate correlates with the mRNA synthesis and decay rates (Peshkin et al. 2015).

Jordan Raff, while introducing Ruth Lehmann, mentioned that he remembered her work, where injecting nanos mRNA into the anterior of the embryo caused the formation of an embryo with “essentially 2 bums”. Co-incidentally Ruth Lehmann came back to the “2 bums” embryo in her talk in the context of mitochondrial segregation in primordial germ cells. A second research story she presented was of mitochondrial maturation during germline cyst formation – developmentally regulated folding of the inner mitochondrial membrane into cristae is dependent on ATP-synthase dimer formation (Teixeira et al. 2015).

In a break with tradition, the student and post-doc social did not have a pub quiz, but instead we were put into random pairs and teams to build spaghetti towers and play science Pictionary. It was an excellent way to meet fellow attendees and bond over our total lack of talent at either drawing or building design (or complete mastery of, in a few cases).

WP_20160410_004

WP_20160410_009

Monday was a day packed with scientific goodness – 4 sessions of talks, 2 medal lectures and 2 poster sessions! The sessions of the morning were Cell and Tissue Architecture and Evolution. In the Cell and Tissue Architecture session I listened to Val Wilson talk about neuromesodermal progenitors (NMPs) – bi-fated cells at the caudal end of the mouse embryo who contribute either to the spinal cord or paraxial mesoderm, depending on their position in the progenitor region. She talked about NMP behaviour during the formation of the mid-trunk (Wymeersch et al. 2016). Olivier Hamant went on to talk about the role mechanical forces play in providing growth cues – microtubule dynamics in response to stress give the characteristic shape of sepals in Arabidopsis (Hervieux et al. 2016). Yara Sanchez Corrales showed how tube morphogenesis in the embryonic Drosophila salivary gland occurs. Cell division does not occur during the process and tube formation is driven entirely by cell shape changes and rearrangements. Their live cell imaging approach allows for the cell shape dynamics to be analysed in 3D.

In the Evolution session, I took in the talks of Marie-Ann Felix, Andrew Gillis and Marty Cohn. Marie-Ann Felix presented work aimed at understanding the effect of random mutation at the phenotypic level. They assayed the sensitivity of the vulval precursor cells of C. elegans to fate changes after the accumulation of random mutation and find that the P3.p vulval cell fate is most affected and is sensitive to mutations in many loci. This means that mutational effects can produce altered responsiveness to signalling pathways and, in this view, the P3.p cell fate is evolving the fastest. Andrew Gillis showed that Sonic hedgehog is required for gill arch anteroposterior polarity and for the branchial ray development in the gills of sharks, skates and rays (Chondrichthyans). This finding parallels paired fin development, giving traction to the hypothesis that there is serial homology between paired fins (and tetrapod limbs) and Chondrichthyan gill arches. Marty Cohn talked of the origin of cartilage – while true cartilage is considered to be unique to vertebrates, invertebrates like cuttlefish show cartilage-like tissue that develops via a deeply conserved gene regulatory network (Tarazona et al. 2016).

The afternoon sessions were Hijacking Cell and Developmental Processes and Polarity. In the Hijacking session, Shuchen Zhang presented her work trying to understand the genetic interactions of Sox2 that underpin its dual functions as a regulator of pluripotency in human embryonic stem cells and as a key factor in neural differentiation. Steve Jackson presented work on how cell-based screens in his lab have identified novel drug targets for cancer therapies, focussing on a PARP inhibitor that is now used in chemotherapy to treat hereditary ovarian cancers. In the Polarity session, Takashi Hiiragi showed that the apical domain of cells is instructive for the initial symmetry breaking in early mouse embryonic development by some fantastic live imaging. Nate Goehring showed us how through the use of novel small molecules, his lab has manipulated the activity and localisation of kinase PKC to understand the PAR polarity network in the C. elegans embryo. Ray Keller talked of the “mechanome” and the game plans – convergent extension, epithelial to mesenchymal transition and convergent thickening (driven by changes in cell affinity) – that tissues use to generate the forces required to drive morphogenesis in amphibians (Pfister et al. 2016).

The evening was host to BSCB’s Hooke Medal and BSDB’s Waddington Medal lectures. Tom Surrey was the recipient of this year’s Hooke Medal. He presented 3 facets of his lab’s research into understanding microtubule dynamics. Through impressive time-lapse fluorescence microscopy movies, we were shown the dynamics of microtubule growth, catastrophe (Duellberg et al. 2016) and nucleation (Roostalu et al. 2015) in in vitro reconstitutions. Tom Surrey’s medal lecture (and all other medal lectures of the meeting) can be watched here:

All movies of the 2016 BSCB/BSDB Spring Meeting

The recipient of the Waddington Medal was completely shrouded in secrecy until just minutes before the lecture, Ottoline Leyser (the BSDB president) even engaging the audience in a little guessing game to introduce him. It was Enrico Coen! He started his talk with a series of sketches of bulls by Picasso and posed the question – what is harder, describing something with every detail or capturing its essence? In a very cinematic presentation with beautiful images and movies, videos of collaborations with potter and glass-blower friends set to a lush soundtrack and a live demo of growth conflicts with melting plastic, Enrico Coen gave us the essence of his obsession – the snapdragon flower. The talk strongly resonated with the conference. References were made to it in almost every subsequent session and he might just have convinced everyone to drop everything they are doing and start studying snapdragons and bladderworts. I have it on good authority that he believes a good talk is like the movie High Noon. I know what you’ll be doing at your next lab meeting…

On Tuesday morning I attended the Growth and Cell division session. I heard Anja Geitmann talk about the mechanisms the pollen tube uses to grow towards the ovaries in plants and it genuinely seems a bit of a wrecking ball. Using a microfluidic device her group has been able to measure the pressure the pollen tube can exert – it is about 150kPa. That’s the pressure in a car tyre! Shane Herbert presented data showing that asymmetric cell divisions and Notch-Delta mediated lateral inhibition establishes the hierarchy of motility in the endothelial tip cells that allows for the leader-follower mode of cell migration in angiogenesis and Silvia Santos brought the session to a close by shedding some light on the temporal control of the cell cycle. Mitosis time is typically short and constant and insulated from the timing of early cell cycle phases. This seems to be regulated by the positive feedback of Cdk phosphorylation. Breaking the feedback leads to longer, more variable mitosis that is coupled to the interphase time.

The Graduate Student Symposium was held on Tuesday afternoon. Despite being fraught with technical difficulties, it was one of the most enjoyable and engaging sessions of the meeting. Kudos to the speakers for their quick thinking and improvisation in face of the ‘your-presentation-won’t-play’ challenge! We heard about (and saw, when the computers co-operated) Mycobacterium infection, cell divisions in motile cells and stretched tissues, centrosome clustering in cancers, neuroretinal self-organising aggregates, neural tube lumen formation, neuromesodermal progenitors, segmentation in spiders and flies, zebrafish cilia formation and calcium signalling in angiogenesis.

Uri Alon provided a brief and unexpected (i.e. not in the schedule) interlude titled the ‘The Life Scientific’ before the Woman in Science Medal talk. With a flip chart, a guitar, witty and tuneful songs that required back up singing by the audience, Uri Alon highlighted the need to acknowledge and discuss the emotional and subjective nature of the scientific process. Feeling lost, stuck and being in “the cloud” is all part of doing innovative science. Please, please watch his TED talk on YouTube, whether you are lost in “the cloud” or not. It is Game of Thrones-level essential viewing.

The Woman in Science Medal was awarded to Lidia Vasilieva for her work in understanding mechanisms of gene expression. Lidia began by highlighting the progress made in science to help women achieve their goals and then focussed on her work in understanding the regulation of gene expression. Her lab has discovered that exosome mediated RNA degradation, in co-operation with the splicing machinery, can regulate levels of mRNA (Kilchert 2015).

Abigail Tucker was the recipient of the first Cheryll Tickle medal. The Cheryll Tickle medal is being awarded by the BSDB to a mid-career female scientist for outstanding contributions to her field. And Cheryll Tickle herself was present to award the medal to Abigail Tucker. She quipped that she was rather glad that the BSDB went with her full name for the medal as “the Tickle medal” might suggest an award for something else (but the medal does feature a feather (!)). Abigail Tucker’s talk was a simultaneous career and life retrospective. She presented a career timeline, talking briefly about her PhD and postdoc work before taking us through the current activities of her lab studying the development of opossums, pit vipers and cobras. I imagine that this is the kind of work Indiana Jones would do, if he were a scientist. She also highlighted personal events of great significance on her career timeline. It is both inspiring and heartening to know that it is possible to have a thriving scientific career alongside a family.

Wednesday morning was a bit of tough start thanks to the late-night/early-morning revelry and dance floor antics that followed the conference dinner. But, I did manage to make it for Wendy Bickmore’s opener for the information processing session at 9.30am (!) about enhancer-promoter interactions studied by chromatin conformation capture and single molecule FISH. She was followed by Stefano De Renzis who showed how he can reconstitute invagination in embryonic Drosophila tissues that normally wouldn’t by optogenetically modulating the local actomyosin contractility.

I then caught the last 2 talks of the ageing and regeneration session. Yves Barral showed us how the bud lineage in budding yeast stays immortal – a diffusion barrier made of phytoceramides separates the mother and daughter preventing exchanging of membrane proteins and allows age to accumulate in the mother cell. Allison Bardin talked about mechanisms causing instability of the genome in adult stem Drosophila intestinal stem cells and how this affects homeostasis. Using an X-linked Gal80 construct she showed that mitotic recombination promotes loss of heterozygosity. She also showed that genomic rearrangements in these cells could lead to the spontaneous development of neoplasias in male flies (Siudeja et al. 2015).

Elena Scarpa, recipient of the Beddington medal for the best PhD thesis, presented her work in Roberto Mayor’s lab before Uri Alon brought the conference to a close. Elena showed the role of cadherins and the interplay of intracellular and external forces in contact inhibition of locomotion in migrating neural crest cells (Scarpa et al. 2015). Uri Alon spoke about how quantitative thinking could be brought into discussions of morphology and showed work from his lab where phenotypes had been studied using Pareto optimality. The approach is based on the logic that no phenotype can be good at all tasks and there is a trade-off with respect to the tasks to ensure maximal fitness, leading to optimal phenotypes. These phenotypes fall into simple shapes such as lines and triangles (Pareto fronts), the vertices representing an archetype – phenotypes that are specialised at a single task (Hart et al. 2015).

To sum up my experience at Warwick – I had spent 3 days being inspired by great talks, fascinated by all the new science I had heard, making new friends, having interesting discussions about my project and science in general. I discovered I am as hopeless at art as I am at origami and have no future at all as an architect. I was also strangely buoyed by the knowledge that most of my experiments are destined to fail. I returned home and fell into the dreamless slumber of a happy and exhausted child and woke up refreshed and ready to get lost in “the cloud”.

 

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Molecular mechanisms of neurogenesis in the developing forebrain and peripheral nervous system

Posted by , on 27 July 2016

Closing Date: 15 March 2021

The laboratory of Developmental Genetics is looking for a PhD student to study the molecular mechanisms of neurogenesis in the developing mouse nervous system. The student will have to apply for a FNRS FRIA fellowship (http://www.fnrs.be/index.php/news-fnrs/517-fria-fresh-2016). The deadline for the application is the 30th August 2016.

The unit is located in the Biopark Charleroi Brussels South (http://ibmm.biopark-it.be/bced/), about 25 miles south of Brussels, in the Institute of Molecular Biology and Medecine (IBMM), a leading multidiciplinarity Institute from the faculty of Science and Medecine of the ULB (http://www.ulb.ac.be/rech/inventaire/unites/ULB578.html). The unit is part of the ULB Neuroscience Institute (http://uni.ulb.ac.be/groups/developmental-genetics/). The group is studying the molecular mechanisms that control the transition from neural stem cell to neurons in the developing vertebrate nervous system. The focus is on the role of some transcription factors in the molecular mechanisms that control neural progenitor maintenance, differentiation, and the generation of neuronal diversity. Major ongoing researches focus on the role of Dmrt transcription factors in cerebral cortex development and of Prdm transcription factors in pain perception, in health and diseases.
The laboratory uses in vivo genetic approaches in the mouse as well as gain- and loss-of-function experiments in the frog to approach gene function in the developing embryo.

The candidate will be involved in one of the two following projects:

Project A:

Pain perception has evolved as a warning mechanism to alert organisms to tissue damage and dangerous environments, and is therefore essential for survival. In human, erroneous activation of the pain-sensing system, as in chronic and neuropathic pain, represents a major health burden with insufficient treatment option. New therapeutic options have recently been developed from studies of a small number of individuals with Congenital Insensitivity to Pain (CIP). The majority of these have Mendelelian disorders of painlessness, where disruptive mutations in a single gene are responsible for their inability to sense pain.
Prdm12 has recently been identified as mutated in individuals with CIP (Chen et al., Nature Genet 47, 803-808, 2015). In our laboratory, we have obtained evidence that Prdm12 is crucial for the generation of the nociceptors, the type of neurons that sense noxious stimuli and transfer nociceptive information to the CNS (Nagy et al., Cell Cycle 14, 1799-1808, 2015). Prdm12 belongs to a family of evolutionarily conserved epigenetic regulators that control neuronal specification (Thélie et al., Development 142, 3416-3428, 2015). It is highly and selectively expressed in differentiating nociceptors and remains expressed in these cells post-natally, suggesting that modulating it may be a new route for pain control.
In this project, our aim is to elucidate Prdm12 mechanism of action in nociceptor differentiation during mammalian embryonic development and determine whether its activity also influences nociceptive function in the adulthood. These objectives will be approached through the detailed characterization of Prdm12 null knock-out and transgenic mice and cell lines available or under construction and using state-of-the art genomics, epigenetic, proteomic and electrophysiological approaches.

Projet B:

Understanding the mechanisms that control the generation of distinct types of neurons from multipotent progenitors constitute a major challenge in developmental neurosciences. Transcription factors are at the core of the programs that control cortical development. Two members of the Dmrt family of zinc finger transcription factors, Dmrt3-5, are expressed by cortical progenitors in a similar high caudomedial to low rostrolateral gradient. Our laboratory has shown that Dmrt5, whose mutation in human has been recently associated with microcephaly (Urquhart et al., Clinical Genetics, 2016) is essential for the development of the caudomedial part of the cerebral cortex including the hippocampus and that it plays a direct role in neocortical progenitors in the control of their specification (Saulnier et al., Cereb. Cortex 23, 2552-2567, 2013 ; De Clercq et al., submitted). Recent results of the laboratory indicate that Dmrt3 also contribute to cortical patterning. Despite their importance, the mode of action of Dmrt5 and Dmrt3 in the specification of cortical progenitor identity and in the control of cortical growth remains largely unknown.
In this project, our objective is to understand these mechanisms through the characterization of the phenotype of Dmrt5-/-;Dmrt3-/- double mutant mice and the identification of their in vivo genomic binding sites (using chromatin immunoprecipitation). These studies should provide important insights into the transcriptional mechanisms controling early cortical development.

PhD candidates should be highly motivated and have previous experience in mouse handling, neurobiology or molecular biology. Interested candidates should send their CV including a motivation letter and contact information of at least two previous supervisors able to recommend their research ability to ebellefr@ulb.ac.be

For more information, see our recent work:

Saulnier et al. (2013). The Doublesex Homolog Dmrt5 is Required for the Development of the Caudomedial Cerebral Cortex in Mammals. Cerebral Cortex, 23, 2552-2567.

Nagy V, Cole T, Van Campenhout C, Khoung TM, Leung C, Vermeiren S, Novatchkova M, Wenzel D, Cikes D, Polyansky AA, Kozieradzki I, Meixner A, Bellefroid EJ, Neely GG, Penninger JM. The evolutionarily conserved transcription factor (2015). PRDM12 controls sensory neuron development and pain perception. Cell Cycle. 14, 1799-808.

Thélie et al. (2015). Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus. Development 142, 3416-3428.

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Life’s symphony: a fusion of art and science to display the beauty of development

Posted by , on 26 July 2016

Mark Hintze and Diana Gradinaru introduce their collaborative animation about the wonders of developmental biology.  

How are you built?  How do you become the shape and form that you are? How are your arms the same length?  These questions and many others lead me to study for a PhD in developmental biology. Yet, during my PhD I was often explaining the fundamental ideas about developmental biology to my parents and friends. Having a huge passion for the wonder of the developing embryo, I thought it would be great if this science was more accessible to everyone.

YouTube videos from channels including minutephysics, veritasium and smarter every day do an amazing job of explaining complex phenomenon in an easy and fun format.  I thought a similar format would be a great way to showcase developmental biology and how it attempts to answer the question of how are you formed.

Kings College London runs a scheme providing a grant for a cultural collaboration with an artist to fuse science and art. I applied to this scheme and won a small grant to collaborate with an artist to create an animated video. This scheme put me in collaboration with the brilliant artist and animator Diana Gradinaru. Her amazing creativity helped push the idea from my head into the wonderful animation that you see in the video. Below the video, she tells us how she approached and applied the creative process to animating Life’s Symphony. MH



 

I remember being a pupil at school loving biology. We had the most wonderful collection of hand-painted large-size illustrations of plants and animals (all handsomely dissected on the page). This was in 90s post-communist Romania when illustration was a craft honed by many working-class men and women trying to do their bit for schools. There was so much clarity in the way these artists had represented the simplified world of science for the benefit of our young minds, but they equally reminded me of Victorian studies I had stumbled upon in art history books.

There was a certain effectiveness to the interactivity between the teacher coming to the front of the class explaining these wonders to us; using these studies, the microscope and the ability to render a perfect depiction of the digestive system on the black board.

I was thrilled when Mark proposed a collaboration revolving around his practice. Animation lends itself effectively to science. It is a time-based medium which can implement a range of intriguing drawing styles and can represent abstract concepts with humour and panache. It can draw the viewer in by alternating the delivery of information with moments of ease and laughter.  As I advanced through the ranks at school, the science books we had become more and more rigid and bare. If only science was rendered with more wit and charm, then people would feel less daunted by it and understand that science, far from being an enclosed subject with a clear-cut trajectory, is actually a bewildering realm, constantly evolving and permeating all aspects of our life.

The animation illustrates a journey through developmental biology. Showcasing how species have evolved to use many of the same genes in different ways and at different times to create the shapes and patterns we see in the world before us. We hope that it displays how the formation of the embryo and adult form is much like a symphony. Where many parts must play together at the right moments to create a concordance and harmony allowing development to occur. DG

 


Diana is an animator and illustrator at the Royal College of Art. http://dianagradinaru.tumblr.com/

 

Mark is a postdoc in the Department of Craniofacial Development & Stem Cell Biology in King’s College London

 

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Categories: Education, Outreach, Science Art, Video

How fish grew limbs and moved onto land

Posted by , on 25 July 2016

Fin to limb transition was a crucial evolutionary adaptation necessary for the vertebrate land invasion in the late Devonian around 400 MY ago. Without this key event, I would not be writing this blog, we as a species would definitely not exist, and neither would any other tetrapod. While the gross morphological changes for this process are fairly well understood, the cellular and molecular mechanism controlling these changes remained a total mystery. In our recent publication (Masselink et al, 2016) we identified a unique and novel lineage of cells within the pectoral fins that have been gradually lost throughout tetrapod evolution and regulate the fin to limb transition by modulating FGF8 and FGF24 expression in the Apical Ectodermal Ridge (AER) and the underlying fin bud mesenchyme.

 

Comparative embryological studies by Thorogood and others suggested that a gradual delay and eventual complete disappearance of the AER to Apical Fold (AF) transition was a driving force of evolutionary fin to limb transition (figure 1, Thorogood, 1991). More recent work by Yano experimentally confirms Thorogood’s hypothesis (Yano, 2012). The Apical Ectodermal Ridge, an ectoderm derived structure that covers the underlying mesenchyme of both the fin and limb bud, secretes pro-proliferative factors such as FGF8 to provide cues for distal outgrowth of the underlying mesenchyme. While in tetrapods the AER perdures and eventually undergoes apoptosis, in fish the AER transitions into the AF, which eventually gives rise to the fin paddle and are populated by actinotrichia, non-ossifying collagen ridge fibrils which provide rigidity to the embryonic fin paddle. Thus a gradual delay and eventual complete disappearance of AER to AF transition would not only allow for the disappearance of the fin paddle but the prolonged presence of the AER would also allow for increased distal outgrowth of the underlying mesenchyme.

 

Thorogood’s clock model suggest that the gradual delay and eventual complete disappearance of AER to AF transition during embryonic development is an important step in fin to limb transition.
Thorogood’s clock model suggest that the gradual delay and eventual complete disappearance of AER to AF transition during embryonic development is an important step in fin to limb transition. (Modified from Thorogood, 1991)

 

We identified a novel lineage of fish-specific AER infiltrating cells that control AER to AF transition that also secrete the collagens required for actinotrichia formation (figure 2). We have thus termed these cells Apical Fold Inducing Cells (AFICs). Using 3 different methods (confocal time lapse microscopy, photoconversions, and somite transplantation) we conclusively show these cells have a somitic origin, a lineage which despite decades of lineage tracing experiments was never identified in tetrapods, suggesting that this is indeed a process unique to fish. Metronidazole and laser mediated ablation were used to selectively ablate AFICs, resulting in fins to form with certain limb-like characteristics. Specifically we observed phenotypes consisting of an expanded mesenchyme, a disruption in AF formation, and a loss of actinotrichia, we also observed an increased expression of FGF8 in the AER and a delay of FGF24 translocation from the mesenchyme to the AER. Inhibition of FGF signalling by treatment with the FGF inhibitor SU5402 completely blocks the increased proliferative response in the mesenchyme, and thus provides a molecular basis for the fin to limb transition.

 

AFIC infiltration into the AER controls fin fold induction. AFICs have a shared somitic origin with the muscle progenitor pool (green) and migrate into the AER (yellow). Upon infiltration into the AER, the AER folds onto itself and forms the AF (red). This infiltration event is absent in tetrapods such as mouse and chicken. AFICs have a dual role in inducing fin fold formation and secreting collagens needed for actinotrichia formation.
AFIC infiltration into the AER controls fin fold induction. AFICs have a shared somitic origin with the muscle progenitor pool (green) and migrate into the AER (yellow). Upon infiltration into the AER, the AER folds onto itself and forms the AF (red). This infiltration event is absent in tetrapods such as mouse and chicken, which have an AER until much later in development until it apoptosis away. The continued exposure to AER derived pro-proliferative signals, allow for the expansion of endoskeletal and myogenic tissue.

 

The induction of the fin fold and actinotrichia formation are two distinct processes, both controlled by AFICs. We have shown AFICs to consistently localize to the distal edge of the actinotrichia, and secrete actinotrichia-associated collagens. The loss of actinotrichia -by knockdown of Actinoidin 1 and 2- results in a fin fold defect but not an expansion of the underlying mesenchyme (Zhang, 2010). Thus while AFICs are essential for actinotrichia formation they play a second role in blocking the expansion of the fin bud mesenchyme, likely through fin fold induction and the subsequent modulation of FGF8 and FGF24.

 

To interrogate the function of AFICs in key phylogenetic representatives of the jawed vertebrate (gnathostome) lineage, we took advantage of the Collagen1a1a antibody that detects zebrafish AFICs. The extant gnathostome lineage is broadly made up of sharks, ray-finned fish and lobe-finned fish. Species within each group were selected based on availability. An active breeding facility of the small benthic Epaulette shark was established providing access to embryonic tissue, while frozen tissue sections of embryos from both the American paddlefish (basal ray-finned species) and the Australian lungfish (lobe-finned species) were fortunately available. We found that both the timing of residency and number of AFICs are gradually reduced throughout evolutionary representatives. While the epaulette shark contains a large number of AFICs in the AER at an early stage of embryonic development, this is already delayed in timing and reduced in number in the American paddlefish. Most strikingly the Australian lungfish, a species that abuts the tetrapod lineage contains very few AFICs, which infiltrate at a late stage, and are lost all together at later stages of development. The total number of AFICs and their timing of residence is in line with the phylogenetic sampling these species present and support Thorogood’s clock model.

 

While our results reinforce the validity of Thorogood’s clock model, and provide a cellular framework for the changes that had to occur during fin to limb transition, they open many new questions. What controls AFIC infiltration, and what controls its timing? At this point we can only speculate. AFICs migrate in a pool of muscle progenitors into the embryonic fin bud. Here they migrate through the basement membrane into the AER. While active migration through the basement membrane is very likely to be important, this does not in and of itself explain the temporal differences observed between species. Muscle progenitors are spread throughout the zebrafish fin bud mesenchyme, coming into direct contact with the basement membrane that separates the AER from the underlying mesenchyme. In contrast, in both chicken and mice the muscle progenitors in early limb buds are restricted to the proximal region of the mesenchyme and do not come into direct contact with the basement membrane. As such, it is possible to imagine that the time between fin/limb field establishment, and muscle delamination and subsequent migration might be essential.

 

References:

  1. Masselink, W. et al. A somitic contribution to the apical ectodermal ridge is essential for fin formation. Nature doi:10.1038/nature18953 (2016)
  2. Thorogood, P. in Developmental Patterning of the Vertebrate Limb (eds Hinchliffe, J. R. et al.) 347-354 (Springer US, 1991).
  3. Yano, T., Abe, G., Yokoyama, H., Kawakami, K. & Tamura, K. Mechanism of pectoral fin outgrowth in zebrafish development. Development 139, 2916-2925 (2012).
  4. Zhang, J. et al. Loss of fish actinotrichia proteins and the fin-to-limb transition. Nature 466, 234-237 (2010).
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Categories: Research

From our sister journals – July 2016

Posted by , on 25 July 2016

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


CoB_DisModMech_AW_RGB

 

 

 

 

Aging zebrafish an ideal model

fishMice have been the traditional model of choice
for investigating telomere shortening in aging, but zebrafish provide an upcoming complementary system with well-conserved physiology. Ferreira and colleagues discuss how fishes have helped our understanding of how telomere attrition contributes to cellular senescence, organ dysfunction and disease. [OA]

 

Diverse phenotypes in neurofibromatosis models

neuro modelNeurofibromatosis type 1 is characterised by nerve sheath tumours but also has significant clinical heterogeneity. Robert Kesterson and colleagues show that two mouse models carrying NF1 patient-specific mutations have distinct effects on embryonic development, neurofibromin function and plexiform neurofibroma formation, with implications for therapeutic studies. [OA]


CoB_BioOpen_AW

 

 

 

bridgeMaternal effects of chromosomal abnormalities

Early emerging problems during oogenesis, such as DNA double-strand breaks, can affect chromosome duplication and segregation in embryogenesis in Drosophila, Andreas Kegel and
colleagues report. Moreover, environmental cues including temperature are important for proper oogenesis. [OA]

 

 

Antibodies light up membranemembrane antibodyies traffic

Sean Munro and
colleagues report the generation and
characterisation of a toolkit of
monoclonal and polyclonal antibodies for labelling the major compartments of the secretory and endocytic pathways in flies, and demonstrate their applicability in multiple cell types. [OA]


Journal typography

 

 

 

 

SXen spindleperm centrosomes defines spindle assembly

Isabelle Vernos and colleagues use a Xenopus egg extract system to analyse how the first embryonic spindle is formed, and find that the duplicated sperm centrosomes define the kinetics of spindle bipolarization, ensuring their own inheritance to the daughter cells.

 

 

Probing chromatin in living cellschromatibody

Gladys Mirey and colleagues present Chromatibody, a
genetically encoded single-domain antibody that binds in a non-invasive manner to the heterodimer of H2A-H2B histones across eukaryotes. This tool allows real time chromatin imaging across eukaryotes, as well as a means to target proteins to chromatin. [OA]

 

 

An overview of Myosin-I motors

In their Cell Science at a Glance poster and article, Betsy McIntosh and Michael Ostap illustrate the proposed functions of metazoan myosin-I molecular motors, examining structural, biochemical, mechanical and cell biological evidence.


Journal typography

 

 

 

 

 Smaller broods promote quicker endothermybluetit

Jan-Åke Nilsson and colleagues show that the ability of blue tit chicks to generate their own body heat is influenced by the size of the brood they grow up in, with chicks from smaller broods becoming endothermic earlier than those from larger broods.

 

 

 

 

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Categories: Research

Postdoc: Comparative epithelial morphogenesis

Posted by , on 23 July 2016

Closing Date: 15 March 2021

From autumn 2016, a postdoctoral research position is available in the Panfilio lab to investigate morphogenesis of the insect extraembryonic (EE) membranes. These simple epithelia are highly dynamic in their role as transient, protective covers for the embryo. The aim is to understand how EE morphogenesis works at multiple levels of biological organization, from cellular ultrastructure to coordination between tissue sheets. The primary research species for the project is the red flour beetle, Tribolium castaneum, an excellent model for studying interactions between developing epithelia via fluorescent live imaging and sophisticated genetic approaches (see the lab’s recent publications in eLife 5:e13834, and Development doi:10.1242/dev.133280).

 

extraembryonic morphogenesis
extraembryonic cell shape changes during tissue remodeling

 

The lab is in the Institute for Developmental Biology, University of Cologne, Germany (lab web page: http://tinyurl.com/c24gpte), and has research and collaboration links with other evolutionary, developmental, and insect labs across the Biology Department of the university. With one million inhabitants, Cologne is an international, vibrant city that is well connected within western Europe.

 

Successful applicants will have a strong interest in developmental genetics and imaging, demonstrated by holding a Ph.D. degree and at least one first author publication in a relevant field. Required skills include standard developmental genetics techniques associated with RNAi, tissue staining, and conventional light microscopy. Experience with electron microscopy, quantitative analysis of multidimensional imaging data, transgenesis, and/or transcriptomics is desired. Depending on expertise and interest, there are possibilities for the applicant to develop his/her own research program among the topics of dynamic tissue adhesion, remodeling of the extracellular environment, and comparative transcriptional profiling. The working language of the lab is English, and strong oral and written communication skills are expected.

 

The position is for one year in the first instance with the possibility for annual extensions. The University of Cologne is an equal opportunity employer in compliance with German disability laws. Women and persons with disabilities are strongly encouraged to apply.

 

To apply send a research statement, CV, starting date availability, and contact details (including e-mail address and phone number) for two references as a single PDF file to Kristen.Panfilio@alum.swarthmore.edu. Informal enquiries to further discuss the position are welcome. All applications will be considered until 20 August 2016.

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