Today’s paper comes from the final issue of Development for 2016, and reveals a link between bioelectricity and reactive oxygen species during tail regeneration in Xenopus. We caught up with first author Fernando Ferreira and his advisor Min Zhao, Professor in Dermatology at UC Davis.

So Min, can you give me the brief history of your lab, and what questions you are interested in?

MZ The main goal of my lab is to electrically heal wounds and regenerate tissues. Demonstrated over one and half centuries ago, the minute electric signals naturally produced at wounds are very poorly understood and appreciated. Epithelial cells and many other types of cells follow the guidance of the electric signals and migrate and grow directionally. We demonstrated that in epithelial sheets, the guidance effect of physiological electric signals overrides other co-existing guidance cues.

I had medical training in trauma with Zhengguo Wang, one of the founding fathers of trauma surgery in China. I then had research training with Geoffrey Burnstock at University College London, and Colin McCaig and John Forrester at University of Aberdeen. I started my lab at the University of Aberdeen with a Welcome Trust University Award and held professor/personal chair and honorary consultant positions at University of Aberdeen and Aberdeen Royal Infirmary (Scotland), before moving to University of California at Davis to take up a professorship in the Department of Dermatology and Department of Ophthalmology.

Supported by grants from NIH, NSF, California Institute of Regenerative Medicine and other federal and state agencies, my lab is interested in answering the following questions:

1. How do cells sense and respond to physiological electric fields?
2. How are the wound electric currents/fields produced and regulated?
3. Can we exploit the “electrical signalling” to enhance wound healing and induce regeneration?

And Fernando, how did you end up in Min’s lab?

FF During my Master’s degree, my adviser and Min met in an international conference. In the discussion they mentioned me; on arrival, my adviser told me that Min’s lab would be willing to host me and that could be an opportunity that I probably should not let escape. By this time, I already knew and admired much of Min’s work and thought it could be an excellent opportunity to test some old and new ideas falling within the framework of his lab. Thus, naturally, I readily set the goal to work with him.

Meanwhile, however, I applied for other closer positions, but I was oddly satisfied or left with a bitter-sweet feeling after receiving no or negative responses; I guess that this proved that I really wanted to join Min’s lab. Things aren’t straightforward though, and after a considerable despair for not getting a 1 year long Fulbright grant to visit Min’s lab, I took a risky move and entered a PhD programme in the Portuguese university (Minho) without funding. I was working in non-scientific part-time jobs to cover the tuition fees and, simultaneously, applied for a studentship grant sponsored by the Portuguese Science and Technology Foundation (FCT). With the Fulbright denial lingering in my mind, I had low expectations. Fortunately, I got the grant and after a way too long “quarantine” process (~8 months), I finally joined the lab in the USA…

It is pressing and fair to recognise that after joining the University of Minho, I received precious encouragement and help from the PhD programme professors and especially my supervisor Andreia Gomes, who accepted me without second thought, always supported me and gifted me with wise advice. All the happiness and sorrow of this journey, allied with the sheer size of the Atlantic Ocean plus the departure delay, made the farewell from family particularly hard; it is a natural cliche to be grateful for family care and support, and undoubtedly I am.

Do you think bioelectricity outside of the nervous system is adequately appreciated in developmental and regenerative biology?

MZ Bioelectricity is not as adequately appreciated in developmental and regenerative biology as I’d wish, which I believe perhaps is due to the following. Research in bioelectricity (not the traditional electrophysiology) was restarted by Lionel Jaffe and his students Richard Borgens, Richard Nuccitelli and Ken Robinson with some wonderful results from the 1960s-1990s. This happened in an era that coincided with the revolutionary discovery of the double helix and the great advances in biology that ensued. Genetic, molecular and biochemical mechanisms are in the lime light of biology, including developmental and regenerative biology. Great advances in technologies and tools in genetics and molecular biology provided developmental and regenerative biologists with powerful tools to understand some of the most fundamental mechanisms. Research technology in bioelectricity, however, has since stayed virtually unchanged. It is also worthwhile to mention that some “charlatan claims” in bioelectricity have tarnished and discredited this field.

“Great advances in technologies and tools in genetics and molecular biology provided developmental and regenerative biologists with powerful tools to understand some of the most fundamental mechanisms. Research technology in bioelectricity, however, has since stayed virtually unchanged”

Bioelectricity is therefore off the radar of most developmental and regenerative biologists. Very few laboratories have continued the efforts in bioelectricity, for example Michael Levin at Tufts University, USA and Colin McCaig at University of Aberdeen, Scotland. Some of their research has provided very impressive results in combination with genetics and molecular biology.

Was anything known about the connection between reactive oxygen species (ROS) and bioelectricity in regeneration before your paper?

MZ & FF Strictly in regeneration, we couldn’t find studies demonstrating a direct connection between redox and bioelectric states. When we started this study we already knew – from decades old evidence – that electric currents were important for a successful regeneration, especially in amphibians; however, no evidence existed about ROS (excluding wound healing in small-scale injuries). Then, a wave of papers came, showing that ROS were also required for regeneration in widespread models, such as Xenopus tadpoles and adult zebrafish. The link between ROS and bioelectricity (membrane potential, transepithelial potential (TEP) and electric currents/fields), remained, however, elusive. In the regeneration field, our study thus appeared in a timely fashion to link the fairly old but re-emerging field of bioelectricity with the emergent field of redox biology.

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

MZ & FF The general take home message is that redox and bioelectric activities interact during regeneration. More specifically, there is a two-way regulation of bioelectric activities by NADPH oxidases: the driven electron flow depolarizes the membrane potential, whereas the produced H₂O₂ increases the magnitude of TEP (positive inside) and switches the direction of electric current (to inward) in the regeneration bud. The depletion of ROS during the regenerative period mimics the abnormally low TEP and non-reversed electric currents measured during the refractory (non-regenerative) period. The external application of H₂O₂ for a short period normalizes the bioelectric activities and, by doing so, rescues and induces regeneration. External H₂O₂ was also inductive enough to form ectopic tails in injuries severing the spinal cord during the regenerative period. Finally and molecularly speaking, H₂O₂ regulates voltage-gated Na⁺ channels in order to modulate regeneration.

Your paper ends with a model including the proposition that immediately post-amputation, an electrical signal activates the redox signal. How did you come to this hypothesis?

MZ & FF To better understand this hypothesis we need to go back a bit and point out the underlying assumptions. One of the highlights of this study is that ROS are immediately required for regeneration. Those ROS are produced from NADPH oxidases, holoenzymes with complex assembly and regulation; therefore, an ultra-fast signal must activate the enzyme to generate sufficient ROS for the task ahead.

One of the highlights of this study is that ROS are immediately required for regeneration…an ultra-fast signal must activate NADPH oxidases to generate sufficient ROS for the task ahead.

 

An electric short-circuit is an instantaneous response to amputation, which results in the so-called injury current and subsequent electric field. This immediate and automatic electric field is, according to the hypothesis, what activates the NADPH oxidases. In fact, there is some evidence showing that applied electric fields induce production of ROS in cells in vitro. We are currently designing experiments to test this hypothesis during regeneration. If true, a redox-bioelectric feedback module would exist in regeneration. This is, the injury-induced electric signals activate the upstream redox signals that regulate downstream electric signals. With caution, we think that the now hypothetical feedback module could be used as theoretical evidence, because it could allow a more tight or efficient regulation of regeneration owing to evolution.

Before speculating or designing more experiments to understand how the electric fields would activate the NADPH oxidases, it is more pressing to test whether the hypothesis is true.

How do you think your mechanism might relate to the ‘canonical’ intercellular signalling pathways that are also involved in regeneration?

MZ & FF The integration between ROS and bioelectric activities occurs very early in the regeneration process. Many of the ‘canonical’ signalling pathways, such as Wnt, BMP and Notch, appear to be activated later on. By itself, this may indicate that those pathways are regulated by ROS and/or bioelectricity, i.e., act downstream. In fact, several studies in the regeneration context have shown that ROS or bioelectricity, independently, regulate some signalling pathways (and also cell behaviours), such as Wnt, FGF and Delta.

Given the high penetrance in regeneration, we think that pathways like the ones already mentioned and others might be affected by redox and bioelectric activities; we also think that follow up studies will unveil this, aiming for a higher level of mechanistic integration in regeneration.

Why do you think the H₂O₂ treatment induced the formation of ectopic tails?

MZ & FF The induction of ectopic tails was a thrilling finding, but it is important to note that the purpose of the assay was to check whether H₂O₂ induced ectopic tails and not why; the why deserves further research. That said, studies found that fin wounds in both Xenopus tadpoles and adult zebrafish generate ROS, likely H₂O₂. Unpublished results from us show that blocking the production of ROS impairs healing in Xenopus fin wounds. Therefore, we think that a threshold of H₂O₂ could define or tune the morphogenetic outcome, meaning that if the threshold is passed we may get an ectopic tail instead of just healing.

“The induction of ectopic tails was a thrilling finding”

Mechanistically speaking, another study found that Wnt signalling induced ectopic tails in the same model as ours. H₂O₂ could thus regulate Wnt for the same purpose, a pathway that could be mediated by bioelectric activities. Not mutually exclusive, another, maybe more speculative, possibility is an analogy with the accessory limb and blastema formation in axolotls and Xenopus, respectively. To induce them, it is required extra neuronal tissue, usually a deviated nerve. The incision we made in the tail severed the spinal cord, therefore, H₂O₂ treatment could, maybe via bioelectricity, affect the neuronal tissue so it becomes inductive.

When doing the research, was there a particularly exciting result or eureka moment that has stayed with you?

FF As many have at one point or another, I had the privilege to experience both life-guiding eureka moments and exciting results. A first eureka-like moment occurred back in my last bachelor year. Anxiously to find what path to follow, I learned about ROS and the caudal regeneration in lizards came to my mind. I had a minor thought experiment: I grabbed a common lizard making it autotomize the tail; with the inner tissues now exposed to the atmosphere, I imagined the oxygen entering the amputation plane down its chemical gradient and then pictured its transformation into ROS; as the levels rose, ROS alarmed local cells that something went wrong and triggered regeneration without any delay. In my innocence at the time, I let this single moment guide me through science ever since; there is no regret!

A second eureka-like moment occurred just before my arrival in the USA. When analysing a review paper, I read that the NADPH oxidases are electrogenic; this triggered a late night chain reaction that led me to the core of this manuscript. As NADPH oxidases work, they transfer electrons through the plasma membrane, so I thought that this was the origin of the membrane depolarization previously shown in regeneration. Then, I thought that since ROS are produced, these would, in turn, affect other facets of the bioelectric phenomena, namely electric currents.

“When analysing a review paper, I read that the NADPH oxidases are electrogenic; this triggered a late night chain reaction that led me to the core of this manuscript”

During the research, the exciting moments were when I was performing the critical experiments testing the redox-bioelectric crosstalk during regeneration. I blocked the production of ROS and imaged the membrane potential and measured the electric currents; during experiments, before getting the positive evidence, I was lightly sweating and my hands and belly were shivering. I know that these “symptoms” are analogous of a romantic encounter, guess that made them even more exciting!

Other unforgettable exciting moment was when, in the very first attempt, I saw a well-defined ectopic tail induced by H₂O₂. I was so impressed by it that I was childish enough to call other lab members to see an undisclosed “hopeful monster” in the microscope.

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

FF Other than now and then when, by procedural vicissitudes – for example, compromised batches of tadpoles (fungal infection, deficient animals, etc.), or all electrodes ending up breaking when touched, or readings were too noisy or strange because the earth wire was somehow disconnected – or for no obvious reason, experiments didn’t work out, I didn’t have any moments of frustration or despair worth noting. If you are surprised, so am I; not having major setbacks by the end of this manuscript surprised me and sometimes even “scared” me, since frustrations are a common theme in the research process and I really don’t want to think that the hypothesis and experimental design put forth were bullet proof. So, for modesty’s sake let’s just call it ‘beginners luck’; probably, the use of well-established techniques and methods helped. Just to highlight the surprise, we are about to submit a new study, where I had my share of despair moments, which I guess covers their absence in this paper, or at least I joke in that way! In fact, I was fortunate enough to get some serendipitous findings which we might end up following.

And finally, Min: where do you think this work will take you next?

MZ We followed an interdisciplinary approach hoping to merge apparently disparate research fields during regeneration. We think that this approach is important and potentially rewarding, and so several lines of research can be pursued with that in mind. We will have at least two exciting possible directions. One is to detail the molecular mechanisms of the redox-bioelectric interplay and to integrate them with ‘canonical’ signalling pathways in the Xenopus and other regeneration models. To help, we are currently establishing a redox and bioelectric sensor facility in the lab. The other is to take advantage of some of the cutting-edge technologies in wound healing and tissue regeneration in mammals. It appears that we are able to manipulate local electric fields and/or redox activities. A combined approach may provide promising therapies for chronic and non-healing wounds.

“I would be tempted to propose a term, “electrobiology”, hoping to suggest that electricity in biology has significant roles”

Evidence is accumulating suggesting bioelectricity as a different layer of mechanism, usually very upstream, together with the fundamental genetics and molecular/cellular processes that orchestrate during development and regeneration. I would be tempted to propose a term, “electrobiology”, hoping to suggest that electricity in biology has significant roles, in contrast to the more than the phenomenological nature of the word “bioelectricity”.

Fernando Ferreira, Guillaume Luxardi, Brian Reid, Min Zhao. 2016. Early bioelectric activities mediate redox-modulated regeneration. Development 143: 4582-4594. 

Browse the People Behind the Papers archive here. 

(4 votes)

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A post-doctoral research associate position in the Department of Zoology, located in Central Cambridge on Downing Street, is available from 1 March 2017 for up to thirty-six months. This is a Leverhulme Trust-funded post, to work with Dr. Andrew Gillis on the embryonic development of gill arch appendages in a cartilaginous fish, the little skate (Leucoraja erinacea).

Cartilaginous fishes possess paired appendages (branchial rays) that project from their gill arches, and over a century ago, Carl Gegenbaur famously proposed that such appendages represent the evolutionary antecedents of paired fins and limbs. We have recently found evidence of developmental parallels between the branchial rays of cartilaginous fishes and the fins/limbs of jawed vertebrates. We now wish to further dissect mechanisms underlying the development of skate branchial rays, in order to test Gegenbaur’s classical hypothesis of gill arch-paired fin serial homology. Duties will include the design and execution of experiments to test for shared embryonic origin, gene regulatory and patterning mechanisms between branchial rays and fins/limbs, and the preparation of results for publication.

The successful applicant should have a Ph.D., completed or completion imminent, in developmental biology, evolutionary biology, comparative anatomy or a related field, with a strong interest in evolutionary-developmental biology. Prior molecular biology and/or bioinformatic training would be beneficial. Skate brood stock is maintained at the Marine Biological Laboratory in Woods Hole, U.S.A., so willingness to travel to the MBL during summer months for experimental work with skate embryos would be beneficial. Enthusiasm, determination and the capacity to work independently are essential.

Further information on this vacancy may be found here.

The closing date for applications is Monday, 23 January 2017. To apply online, please visit http://www.jobs.cam.ac.uk/job/12377/ and click on the ‘Apply’ button. This will route you to the University’s Web Recruitment System, where you will need to register an account (if you have not already) and log in before completing the online application form.

Please quote reference PF10959 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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Biomedical research is experiencing what has been termed a ‘reproducibility crisis’. There is much talk about how we can improve the rigor and robustness of our research to increase its value and predictiveness. Many remedies are being discussed, such as increasing statistical power, reducing bias by improving internal validity, fostering transparency by open data policies, and publication of NULL results, among many others. In general, this debate is about increasing the quality of our research. Errors, mistakes and mishaps negatively impact on quality. In a work environment as complex as experimental biomedical research a substantial number of errors may occur on a daily basis, which can jeopardize the quality of our work, and may waste resources, or even endanger personel. Surprisingly, the issue of errors, and how to avoid them, has not yet received any attention in the current ‘biomedical research waste’ debate.

There is no way for professionals to not make mistakes from time to time. What really makes a difference is how we deal with such mistakes. Often mistakes can even teach you that a certain strategy may not be sufficient to solve a given problem. In any case, we do not want to keep repeating mistakes, so we have to learn how to avoid them. However, while this may work for the person responsible for or witnessing a mistake, this information is lost for the surrounding community if not properly communicated. While most people may consider it as helpful to learn from other’s mistakes, they may not want to admit and communicate their own mistakes in front of others. Potential reasons include just feeling ashamed or concerns that a certain mistake may put the own position at risk. So the question is: How can we facilitate the reporting of errors in an open, non-punitive manner?

Systems to report critical errors and incidents were already in place during World War II in order to improve safety for military pilots. Today, critical incident reporting systems (CIRS) can be found in the energy sector, aviation, or clinical medicine. The basic concept of such CIR systems is that they offer a way to report mistakes and (critical) incidents without the need to reveal the identity of the reporter. While CIRS are mandatory in the context of clinical medicine, structured ways to report errors are virtually unknown in the context of academic preclinical research.

We have therefore developed, tested, and implemented a CIRS for biomedical research. The Department of Experimental Neurology, with approximately 100 students, researchers, and technicians, carries out academic research in preclinical biomedicine. At the moment nine workgroups with different research focus, reaching from spinal cord injury to neuroimmunology work in our department, using techniques like cell culture, microscopy, MRI, animal behavioral studies, molecular biology or biochemistry.

We first encountered the challenge how to handle errors and critical incidents in a structured way in 2012 when we the decided to implement a quality management system to improve the quality and validity of our research. The system we choose as a framework was the ISO 9001:2008 norm, which requested a statement on how we handle critical incidents. During the implementation process we learned a lot about quality management (QM) in general, since QM is very rare in academic basic research. We therefore had to adapt and even invent many features of our QM on the go. The development of CIRS for the laboratory environment is a typical example for this learning by doing approach.

Our first version of an error reporting system was paper based, just a form sheet on our pinboard. While this form already covered all necessary questions, it was almost completely ignored by our staff. Trying to understand the reasons, we found out that the paper version was not convenient and more importantly, not confidential enough. Our colleagues were worried that the reported incident could reveal their identity and may put their position at risk. Acknowledging this obstacle, the idea was born to use an online tool, which does not require user specific information, nor requiring or logging any personal information. Since there was no out of the box system available, which met out needs (anonymous, browser based, structured, but not as complex as a medical CIRS), Sebastian Major, a member of our department designed the LabCIRS from the scratch. The source code and a documentation can be found at github.

After some fine tuning and beta testing, LabCIRS went online at the end of 2013. This is how it works for the researcher (student, technician, postdoc, etc.): First, one has to log in with a shared login for all department members which does not point to a single user. The system is bilingual (English /German), so depending on their preferences, users can choose the language they feel more comfortable with. After login, the user sees all formerly published incidents and can either search and read through them or report a new incident.

While reporting an incident the reporter can assign a date, describe what happened, and if make suggestions on how to avoid the event in the future. In addition, images can be uploaded, and as a last step, the reporter is asked if the reported incident should be available for all users of the LabCIRS, or reported just to responsible personel.

The reported incident is then checked by a “reviewer” who has privileged access to LabCIRS. This reviewer translates the reported incident and makes sure no personal information is reported. In a next step, the reported incident is internally discussed in our monthly quality meeting with the focus on how the avoid a recurrence of the same incident in the future. Then, if the reporter agreed, it is published inside the LabCIRS, via mail and in addition reported at one of our weekly department meetings.

While it is of course desirable to make all reported incidents available to the public, we found it important to leave this decision to the reporter.

At the very beginning, only about half of the reported entries were cleared by the reporter to be openly published in the department. Over time, however, when it became evident to the reporters that reporting is appreciated and the idea is not to blame anyone, but to learn from mistakes and, if possible, to avoid them in the future, the mindset slowly changed. For more than one year now, all of the reported incidents are cleared for publication. This demonstrates a change in error culture, away from hiding mistakes towards an open discussion and prevention.

Clearly, it is not software which makes people change their minds about quality and error culture, but for us, the LabCIRS was and is a helpful tool helping us in this process.

If you would like to give it try for yourself to check out if this could be useful for you as well, feel free to check it out under http://labcirs.charite.de and download it (or even commit something) at github.

You can find a more detailed report on our LabCIRS in our publication in PLOS Biology.

(2 votes)

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Here are the highlights from the new issue of Development…the last one of the year!

SETting chromatin state through transcription

Setd5 is a poorly characterised murine member of the SET domain family, generally associated with histone methyltransferase activity. However, the closest homologues of Setd5 are thought to be catalytically inactive, and have instead been associated with the regulation of histone acetylation levels at genes. On p. 4595, Anna Osipovich and colleagues generate Setd5 mutant mice and embryonic stem cells (mESCs). Setd5 homozygosity is lethal, with mutant embryos failing to survive beyond E10.5. Phenotypically, mutants display multiple defects, most notably in the cardiovascular system. Globally, cell proliferation is impaired and apoptosis increased. The mESC system reveals phenotypes consistent with the in vivo observations, including impaired differentiation down the cardiac lineage, while RNA-seq analysis shows that over 10% of coding genes are dysregulated in mutant cells – including key genes involved in cardiovascular development. Setd5 interacts with members of the polymerase-associated factor 1 complex (PAF1C) and NCoR co-repressor complex, the latter of which mediates gene silencing through histone deacetylation. Although the precise developmental consequences of Setd5 ablation have yet to be fully understood, this work suggests that this protein might cooperate with PAF1C and NCoR to mediate co-transcriptional regulation of histone acetylation and gene activity.

A new view on implantation

Implantation of the blastocyst into the uterus is obviously a critical step in mammalian development, yet we understand very little about the three-dimensional environment into which the embryo implants. It is known that, in mouse at least, blastocysts attach in uterine crypts, but how these form and whether such structures are also found in human is unclear. Here (p. 4749), Diana Laird and colleagues seek to provide new insights into uterine architecture before, during and after implantation. The authors develop sophisticated imaging and computational tools to characterise the 3D structure of the mouse uterine luminal and glandular epithelium, showing that the pattern of folding alters dramatically prior to implantation, giving rise to folds that overlap with structures described as crypts. Moreover, uterine glands reorient towards the site of implantation and show structural changes. This technology is able to detect architectural defects in mutant animals (such as aberrant luminal folding in Wnt5a mutants) and can also be applied to human uterus samples – as well as, potentially, other organs. This work provides an unprecedented view of the environment into which the embryo implants, and opens up avenues for further analysis of the mechanisms underlying uterine restructuring during early pregnancy.

Sparking regeneration with ROS

During regeneration, multiple signalling pathways act to coordinate the various processes required to regenerate an injured organ or body part. Both reactive oxygen species (ROS) and electric currents have been shown to modulate regeneration, but how they exert their effects, and whether their activities might intersect, is poorly understood. Here (p. 4582), Fernando Ferreira, Min Zhao and colleagues set out to address the potential interplay between ROS and bioelectric phenomena using the Xenopustadpole tail regeneration model. They uncover a dual role for NADPH oxidases in regulating bioelectric activities: NADPH oxidase-driven electron flow induces membrane depolarisation, while the hydrogen peroxide produced leads to activation of sodium channels in cell membranes of the regeneration bud, with consequent effects on transepithelial potential and electric currents that mediate regeneration. Moreover, external application of hydrogen peroxide can induce tail regeneration during the refractory period in the tadpole’s life – when regeneration is normally blocked – as well as the formation of ectopic tails at injury sites during the regenerative period. Although the mechanisms by which bioelectric activities might modulate the cellular processes required for regeneration still require further investigation, this work links two previously unconnected regulators of regeneration and provides convincing evidence for redox-bioelectric integration in this context.

Robust transcriptional control of multiciliogenesis

Multiciliated cells (MCCs) are found on various epithelia where they drive fluid flow – such as in the airways, the brain ventricles, and the skin of Xenopus embryos. Their differentiation is known to be coordinated by transcriptional regulators such as Multicilin and Gemc1, as well as by the key transcription factor Foxj1, which is also required for cilium formation in cells that produce just a single motile cilium. On p. 4654, Chris Kintner and colleagues identify another transcription factor required for proper differentiation of MCCs – Foxn4. Through an elegant combination of morpholino and CRISPR-based loss-of-function technologies, they show that loss of foxn4 disrupts docking of basal bodies to the cell surface – an essential prerequisite for cilium extension. This phenotype is reminiscent of the foxj1 phenotype, except that it largely recovers over time and that foxn4 has no apparent effect on cells with a single cilium. Through RNAseq and ChIPseq analyses, the authors find that Foxn4 promotes expression of a subset of Foxj1 targets. They propose that Foxn4, acting downstream of Multicilin, might be required to promote high-level expression of Foxj1 target genes that may be necessary for efficient generation of multiple cilia.

PLUS

An interview with Doug Melton

Doug Melton is Xander University Professor at Harvard University, co-director of the Harvard Stem Cell Institute and a Howard Hughes Medical Institute Investigator. His lab investigates the development of the pancreas, and uses insights from this process to direct the production of insulin-producing beta cells from stem cells. We met Doug at the 2016 Society for Developmental Biology-International Society of Differentiation (SDB-ISD) joint meeting in Boston, USA, where he gave the Jean Brachet Lecture. See the Spotlight article.

Fox transcription factors: from development to disease

Forkhead box (Fox) transcription factors regulate diverse biological processes both during development and throughout adult life. Mutations in many Fox genes are associated with human disease and, as such, various animal models have been generated to study the function of these transcription factors in mechanistic detail. In their Primer, Maria Golson and Klaus Kaestner review these studies and provide an overview of the Fox family, highlighting several key Fox transcription factor families that are important for mammalian development.

The many faces of hematopoietic stem cell heterogeneity

Not all hematopoietic stem cells (HSCs) are alike: they differ in their physical characteristics, they respond to different extrinsic signals, and they have different lineage outputs following transplantation. This  raises questions as to why HSC subtypes exist, how they are generated, and whether HSC heterogeneity affects leukemogenesis or treatment options. In their Review, Mihaela Crisan and Elaine Dzierzak provide a developmental overview of HSC subtypes during embryonic, fetal and adult stages of hematopoiesis and discusses the possible origins and consequences of HSC heterogeneity.

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Department/Location: Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, University of Cambridge

Salary: £29,301-£38,183

Reference: PS10876

Closing date: 08 January 2017

Fixed-term: The funds for this post are available until 30 June 2022 in the first instance.

The Cambridge Stem Cell Institute is a world-leading centre of excellence in stem cell biology and regenerative medicine, supported by the Wellcome Trust and the Medical Research Council (www.stemcells.cam.ac.uk). The Institute comprises over 300 scientists whose research spans fundamental science through to clinical applications. Our vision is to develop a deep understanding of stem cell biology for the prevention and treatment of human disease.

Public Engagement (PE) is an essential part of our work. We seek to provide opportunities for the public to explore and question research developments and for researchers to improve their understanding of public views. The purpose of the PE Manager role is to create and support a community of scientists who recognise the importance of dialogue with the public and who have the skills and opportunities to undertake PE activities. Overall, the CSCI aims to have highly visible public engagement that is woven into all aspects of scientific research and the PE Manager is envisioned to develop this ethos across the institute.

The PE Manager is responsible for the implementation and development of the PE Programme, which includes a wide variety of public events for different target communities, as well as digital engagement activities and professional development training for researchers. The post holder will also be responsible for developing a reward and recognition framework for researcher-led public engagement that aligns with institutional public engagement priorities. The role involves both long-term, strategic planning and detailed event management (see further particulars). The PE Manager will manage one part-time (50%) Events Administrator and there may be opportunities to expand the team from 2018 onwards.

We are seeking an innovative and self-motivated public engagement professional to lead the programme through an exciting phase of growth. As we plan for our move to custom-built premises on the Cambridge Biomedical Campus in 2018, you will need to take the lead on multiple large-scale, innovative projects in order to cement PE in the working culture of our institute.

You will be educated to degree level (or equivalent), ideally in a scientific subject. You will have had experience in a similar role, preferably having managed a small team. You must demonstrate a proven track record in relationship building, event organisation, report writing, and data management. You will have outstanding organisational and administrative experience and be comfortable working to tight deadlines with minimal supervision. You should have demonstrable experience in web-based/social media communication and you should have excellent written and verbal communication and negotiation skills.

The post will work in close collaboration with senior roles in the Admin team, with supervision from the PE steering committee and SCI Administrator and will report to the Institute Director.

To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/12282. This will take you to the role on the University’s Job Opportunities pages. There you will need to click on the ‘Apply online’ button and register an account with the University’s Web Recruitment System (if you have not already) and log in before completing the online application form.

Please upload your current CV and cover letter with your application by Sunday 08 January 2017.

Interviews will be held on the morning of Monday 23 January 2017.

Informal enquiries are also welcome via e-mail to David Kent at dgk23@cam.ac.uk.

Please quote reference PS10876 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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Postdoctoral Research Associate

Craniofacial Biology – University of Southern California Health Science Campus

We are seeking a promising postdoctoral research associate, with expertise in molecular biology and bioinformatics. The program’s goal is to create the next generation of cutting-edge dental and oral health researchers in the U.S. and to shape independent scientists who are able to initiate research programs that will ultimately improve world health.  This appointment provides a broad, interdisciplinary experience preparing postdoctoral researchers to generate new discoveries that identify, prevent, treat and cure diseases of the craniofacial complex. The ideal candidate seeks advanced training in all aspects of molecular and oral biology, bioinformatics and oral pathology.

Postdoctoral associates will thrive in an integrated curriculum that includes mentoring, scientific advancement, career development, publication and grantsmanship.  The curriculum is taught through symposiums, seminars, clinical research centers and collaborate research.  Mentors are committed to helping students transition from scholar to independent investigator in an academic or industry environment.

Position Accountabilities:

• serves as a research associate for the purpose of enhancing and developing research competencies. Participates in planning, designing and conducting highly technical and complex research projects under the direction of a supervising mentor/ personal investigator (PI). May or may not work independently.
• Identifies, researches, compiles and evaluates data sources, background information and/or technology related to area of specialization.
• Analyzes and evaluates research data utilizing computers and provides interpretations requiring significant knowledge of a specialized area of research. Searches literature, utilizing all available resources including electronic, regarding new methodology and designs experiments accordingly.
• Contributes to the development of research documentation for publication and/or prepares technical reports, papers and/or records.
• Operates and maintains sophisticated laboratory/scientific equipment.

Minimum Education: Ph.D. or equivalent doctorate within previous five years

Minimum Experience: 0-1 year

Minimum Field of Expertise:  Education in Molecular Biology, Bioinformatics and/or Biostatistics research with advanced knowledge of equipment, procedures and analysis methods.  US citizenship required.

Preferred Education: Ph.D. in Molecular Biology with experience in Bioinformatics

Preferred Experience: Directly Related Research. Publications in peer-reviewed journals in the same or related field.

Skills: Analysis
Assessment/evaluation
Communication — Written and Oral Skills
Conceptualization and Design
Organization
Planning
Problems identification and Resolution
Project Management
Research
Statistical analysis

Special Instructions to Applicants: A copy of the doctoral diploma or other certification that indicated that the terminal degree has been completed satisfactory is required. If the doctoral candidate has not yet obtained a degree, he/she should provide evidence that a thesis has been approved together with a documented indication of the expected date of formal graduation. It is the responsibility of the faculty mentor to verify documentation. The documentation is to be filed with the Office of Postdoctoral Affairs.

For immediate consideration, please email CV to: Janice Bea (jbea@usc.edu)

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November turned out to be  a bumper month on the Node with posts on research (current and historical), meetings and new resources, as well as interviews and a meeting report. Plus some beautiful science-inspired art. Here are some of our highlights, as well as our pick of the best of the web this month.

Research, resources, and advocacy

We heard about recent research on what a pluripotency transcription factor does during mitosis, how sea stars build their nervous systems, and how fruit flies make blood.

We heard about the 3D atlas of human development, a resource that includes histology sections and interactive 3D PDFs of the stages of human development,  and the team behind the eMouse Atlas told us about their new eLearning resource. We also continued our monthly rounds up of preprints of interest to developmental biology.

Andreas Prokop wrote about why advocacy is crucial for the survival of developmental biology, and why all of us should have our elevator pitch ready. He is keen to hear thoughts on ideas on this issue!

People and places

We got to know a whole bunch of developmental biologists this month, in Development interviews with Paola Arlotta, Kathryn Anderson and David McClay, and in our People Behind the Papers series featuring James Nichols on craniofacial development in zebrafish, and Kristian Franze, Amelia Joy Thompson and Sarah Foster on how the mechanical environment influences axon pathfinding in brain development.

Our latest in the ‘Day in the Life…’ series came from Yuuri Yasuoka in Okinawa, who gave us an insight into working with coral.

We also got to hear an account (by me) of the Spanish Society for Developmental Biology’s annual meeting in beautiful Girona, and about another trip by one of the Company of Biologists’ Travelling fellows, Alessandro Donada, from Paris to Cambridge.

Art and history

We heard from two scientist-cum-artists, Mia Buehr and Beata Edyta Mierzwa, about how cell and developmental biology influenced their art.

Our latest post in the Forgotten Classics series featured two papers from Rosa Beddington, with insights from two people who worked with her, Patrick Tam and Virginia Papaioannou.

Beyond the Node: some internet highlights

• Nipam Patel promoted his beautiful video on squid development, compiled from a decade of Woods Hole Embryology Courses
• In the week of the official opening of The Crick, James Briscoe gave an inside perspective on their hiring policy
• Alfonso Martinez-Arias wrote about the promise of preprints in biomedical sciences, and about what stem and developmental biologists have in common with engineers.
• Brooke Morriswood gave a short guide to writing scientific manuscripts
• A set of papers reported failure to replicate the NgAgo gene-editing method
• An event at the Harvard Law School brought together scientists and ethicists to discuss the 14 day rule for human embryo research
• In the ASCB Newsletter, Peter Walter and Dyche Mullins talkes about the problem with commercial publishing
• Following Theresa May’s announcement of £2billion/year investment in research and development, the RCUK welcomed the news,  and Scienceogram took a look at the numbers
• Ewa Paluch of the MRC LMCB at UCL has been announced as the winner of the BSCB Hooke Medal 2017
• Fredrik Lanner of the Karolinska Institute was named a Wallenberg Academy Fellow
• The FASEB BioArt competition winners were announced, and included some beautiful developmental biology!
• The Allen Institute for Cell Science announced the release of five publically available tagged cell lines
• Over on PLoS Biologue, Jamy Pang gave the story behind his recent work on small non-coding RNAs and fertility
• Paul Knoepfler interviewed Michael Werner about the 21st Century Cures Act
• Oh, and there was an election.

The best tweets

First cell divisions of a C. elegans embryo. Stack rotation in post-processing. His-GFP & Gtub-GFP #lightsheet #celegans pic.twitter.com/TAqeOaTzUv

— Loïc A. Royer 💻🔬⚗️ (@loicaroyer) November 28, 2016

Two color adaptive lightsheet timelapse #adaptive #lightsheet https://t.co/gKleMSDP6w

— Loïc A. Royer 💻🔬⚗️ (@loicaroyer) October 31, 2016

Happy Thanksgiving! Yes, we CT scanned our turkey, and like any good dinosaur biologist, prepared and accessioned the skeleton (OUVC 10789). pic.twitter.com/V2YbF6mF22

— WitmerLab (@WitmerLab) November 24, 2016

Happy Birthday Alfred Henry Sturtevant! From 1913-1928, he determined linear arrangement of Drosophila genes. https://t.co/WwoEvqWHYi pic.twitter.com/Sm73LOZXg3

— A. Sánchez Alvarado (@Planaria1) November 22, 2016

The first issue of @Nature was printed today in 1869. In opening article Huxley writes on obsolescence of theories but permanence of poetry. pic.twitter.com/rNXy5mbyAD

— A. Sánchez Alvarado (@Planaria1) November 4, 2016

~30,000 people are now an author on a bioRxiv preprint :-) #preprintsworking

— Richard Sever (@cshperspectives) November 3, 2016

https://twitter.com/Alexis_Verger/status/803543211146964992

This is one of the simplest and most eloquent quotes about science anywhere…. We'll miss you, @Sue_Lindquist pic.twitter.com/A3qDOmIVzr

— Hunt Willard (@hwillardX) November 1, 2016

We're open! Today @TheCrick opens its doors to the public. Come along and see us opposite St Pancras #insidetheCrick #howdowelook pic.twitter.com/GAb5YfCeuc

— The Crick (@TheCrick) November 2, 2016

We're all aglow about this wonderful infographic by @eleanor_lutz on #bioluminescent creatures: https://t.co/PUWOr8BB9M via @compoundchem pic.twitter.com/z8u7Vcgrsu

— Max Planck Society (@maxplanckpress) November 23, 2016

If Andy Warhol did Zebrafish…. pic.twitter.com/bkrqKNGNPJ

— Cardiff Bioimaging Hub (@CUBioimagingHub) November 21, 2016

ZF skin is beautiful pic.twitter.com/G0TUYobJHt

— MadScientist (@MadS100tist) November 27, 2016

#NHLBI-funded study in zebrafish shows that color-coded stem cells can help shed light on blood disorders, cancer: https://t.co/viCg2EoO34 pic.twitter.com/eylYSUyVEA

— NIH NHLBI (@nih_nhlbi) November 23, 2016

Impressions from a long weekend: the Church of Haeckel. pic.twitter.com/2RlVLwwfZB

— Yogi Jaeger 💙 @yoginho@spore.social (@yoginho) November 1, 2016

Making prizes for the #sciPoet meeting. Seeing some old friends. pic.twitter.com/6NOQVYNvU5

— Adam P. Summers (@Fishguy_FHL) November 13, 2016

https://twitter.com/albertcardona/status/798817679159083009

Just one of the rather brilliant designs from @The_Big_Draw – behold our time-lapse video of the Big Cell being made https://t.co/MIgeMWdw4S pic.twitter.com/aShLsGTA5d

— The Royal Society (@royalsociety) November 9, 2016

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

Chisato Kitazawa and colleagues uncover diversity in the morphological changes of early embryogenesis in closely related sea urchin species.

Ben Steventon and colleagues describe how crainial placode formation in Xenopus involves directional and persistent cell movements

Also using Xenopus, Karl Matter and colleagues identify a link between tight junctions and JNK signalling pathways in eye development.

Staying underwater, Uwe Irion and colleagues link heterotytpic, gap junction-mediated cell interactions with cell morphology during zebrafish skin patterning.

Above ground, Laura Buttitta and colleagues show how a steroid hormone induces two phases of cell cycle exit in Drosophila.

The JCS team featured Celeste Nelson as a Cell Scientist to Watch, whose lab is “focused on studying how groups of cells physically position or turn themselves into tissues.”

R. Kelly Dawe and colleagues investigate chromosome dynamics during meiosis in maize, and show that the process self-corrects as meiosis proceeds.

Graydon Gonsalvez and colleagues demonstrate that a new isoform of Tropomyosin interacts with kinesin to promote RNA localisation.

Martin Humphries and colleagues give an overview of the complex group of proteins that help integrin receptors adhere cells to the ECM.

(These were accidentally posted last month and are reposted here just in case you missed them)

Gabrielle Kardon and colleagues show that TBX3 is responsible for specifying a subset of forelimb muscles, and their attachment to tendons.

Nicholas Pilon and colleagues describe how a mouse line found in a screen for genes involved in neural crest development provides a model for Waardenburg syndrome type 4.

Colin Bingle and colleagues develop an in vitro model of the murine middle ear epithelium, recapitulating cell populations and protein production.

In his Editorial, Senior Editor Ross Cagan gives some tips for those wanting to conduct drug screening in model systems

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Our latest monthly trawl for developmental biology (and other cool) preprints. See June’s introductory post for background, and let us know if we missed anything

This month, we found preprints covering various aspects of plant growth and patterning, a lot of cell biology – including insights into microtubules organisation, RNA localisation and yeast size control – as well as a bunch of tools. One of the most talked about preprints of the month comes from our ‘Away from the bench‘ section: a guide for how to structure scientific papers. Happy reading!

Developmental biology

SmallOrgan 1 plays an essential role in cell proliferation, cell expansion and cadmium uptake in rice. Peng Qin, Jiangbo Hu, Weilan Chen, Guohua Zhang, Jian Li, Shijun Fan, Bin Tu, Xuewei Chen, Yuping W Wang, Shigui Li, Bingtian Ma.

Ubiquitylation activates a peptidase that promotes cleavage and destabilization of its activating E3 ligases and diverse growth regulatory proteins to limit cell proliferation in Arabidopsis. Hui Dong, Jack Dumenil, Fu-Hao Lu, Li Na, Hannes Vanhaeren, Cristin Naumann, Maria Klecker, Rachel Prior, Caroline Smith, Neil McKenzie, Gerhard Saalbach, Liangliang Chen, Tian Xia, Nathalie Gonzalez, Mathilde Seguela, Dirk Inze, Nico Dissmeyer, Yunhai Li, Michael W Bevan

Ancient coding sequences underpin the spatial patterning of gene expression in C4 leaves. Ivan Reyna-Llorens, Steven J Burgess, Ben P Williams, Susan Stanley, Chris Boursnell, Julian M Hibberd

The Tension-sensitive Ion Transport Activity of MSL8 is Critical for its Function in Pollen Hydration and Germination. Eric S. Hamilton, Elizabeth S. Haswell

tRNA-derived small RNAs target transposable element transcripts. Sarah Choudury, Keith Slotkin, German Martinez

Chromatin accessibility dynamics reveal novel functional enhancers in C. elegans. Aaron C Daugherty, Robin Yeo, Jason D Buenrostro, William J Greenleaf, Anshul Kundaje, Anne Brunet

An RNA binding polymer specifies nematode sperm fate. Scott Takeo Aoki, Douglas F Porter, Aman Prasad, Marvin Wickens, Craig A Bingman, Judith Kimble

DIV-1/PolA2 Promotes GLP-1/Notch-Mediated Cellular Events in Caenorhabditis elegans. Dong Suk Yoon, Dong Seok Cha, Myon-Hee Lee

PRDX6 inhibits neurogenesis of neural precursor cells through downregulation of wdfy1 mediated TLR4 signal. Mi Hee Park, Dong Ju Son, Kyoung Tak Nam, So Young Kim, Sang Yeon Oh, Min Ji Song, Hyung Ok Chun, Tae Hyung Lee, Jin Tae Hong

Axonal transcriptome of human stem cell derived neurons. Rebecca L Bigler, Joyce W Kamande, Raluca Dumitru, Mark Niedringhaus, Anne Marion Taylor.

Estimating Drivers of Cell State Transitions Using Gene Regulatory Network Models. Daniel Schlauch, Kimberly Glass, Craig P Hersh, Edwin K Silverman, John Quackenbush

G protein-coupled estrogen receptor regulates heart rate in zebrafish embryos. Shannon N Romano, Hailey E Edwards, Jaclyn Paige Souder, Xiangqin Cui, Daniel A Gorelick

In vivo imaging of coral tissue and skeleton with optical coherence tomography. Daniel Wangpraseurt, Camilla Wentzel, Steven L Jacques, Michael Wagner, Michael Kuhl

Dynamic changes in Sox2 spatio-temporal expression direct the second cell fate decision through Fgf4/Fgfr2 signaling in preimplantation mouse embryos. Tapan Kumar Mistri, Wibowo Arindrarto, Wei Ping Ng, Choayang Wang, Hiong Lim Leng, Lili Sun, Ian Chambers, Thorsten Wohland, Paul Robson

High temporal resolution of gene expression dynamics in developing mouse embryonic stem cells. Brian S Gloss, Bethany Signal, Seth W Cheetham, Franziska Gruhl, Dominik Kaczorowski, Andrew C Perkins, Marcel E Dinger

Functional transcriptomics in diverse intestinal epithelial cell types reveals robust gut microbial sensitivity of microRNAs in intestinal stem cells. Bailey CE Peck, Amanda T Mah, Wendy A Pitman, Shengli Ding, P. Kay Lund, Praveen Sethupathy

Constitutive Immune Activity Promotes Tumorigenesis in Drosophila Intestinal Progenitor Cells. Kristina Petkau, Silvia Guntermann, Edan Foley

Rfx2 stabilizes Foxj1 binding at chromatin loops to enable multiciliated cell gene expression. Ian K Quigley, Chris Kintner

Ageing, TOR and amino acid restriction: a cross-tissue transcriptional network connects GATA factors to Drosophila longevity. Adam J Dobson, Xiaoli He, Eric Blanc, Ekin Bolukbasi, Yodit Feseha, Mingyao Yang, Matthew Piper

Pulse of α-2-macroglobulin and lipocalin-1 in the pregnant uterus of European polecats (Mustela putorius) at the time of implantation. Heli Lindeberg, Richard Burchmore, Malcolm W. Kennedy

Cell biology

A Critical-like Collective State Leads to Long-range Cell Communication in Dictyostelium discoideum Aggregation. Giovanna De Palo, Darvin Yi, Robert Endres

Probing cytoskeletal modulation of passive and active intracellular dynamics using nanobody-functionalized quantum dots. Eugene A Katrukha, Marina Mikhaylova, Hugo X van Brakel, Paul M van Bergen en Henegouwen, Anna Akhmanova, Casper C Hoogenraad, Lukas C Kapitein

Size-Dependent Accumulation of the Mitotic Activator Cdc25 as a Mechanism of Size Control in Fission Yeast. Daniel Keifenheim, Xi-Ming Sun, Edridge D’Souza, Makoto Ohira, Mira Magner, Michael B. Mayhew, Samuel Marguerat, Nicholas Rhind

Microtubule organization within mitotic spindles revealed by serial block face scanning EM and image analysis. Faye M Nixon, Thomas R Honnor, Georgina P Starling, Alison J Beckett, Adam M Johansen, Julia A Brettschneider, Ian A Prior, Stephen J Royle

Microtubules with a twist: a lumenal interrupted helix in human sperm tail microtubules. John M Heumann, Cindi L Schwartz, Azusa Suzuki-Shinjo, Garry Morgan, Per Olov Widlund, Johanna Louise Hoog

Visualizing adenosine to inosine RNA editing in single mammalian cells. Ian A Mellis, Rohit K Gupte, Arjun Raj, Sara H Rouhanifard

An RNA-binding tropomyosin recruits kinesin-1 dynamically to oskar mRNPs. Imre Gaspar, Vasily Sysoev, Artem Komissarov, Anne Ephrussi

Drosophila BEACH domain autophagic adaptor blue cheese shuttles between vesicle populations and is required for an early step in autophagy. Joan Sim, Kathleen Amy Osborne, Irene Argudo Garcia, Artur Matysik, Rachel Kraut

Evolution, etc

Engineered reciprocal chromosome translocations drive high threshold, reversible population replacement in Drosophila. Anna B Buchman, Tobin Ivy, John M Marshall, Omar Akbari, Bruce A. Hay

Recurrent gene duplication leads to diverse repertoires of centromeric histones in Drosophila species. Lisa E. Kursel, Harmit Singh Malik

An annotated draft genome for Radix auricularia (Gastropoda, Mollusca). Tilman Schell, Barbara Feldmeyer, Hanno Schmidt, Bastian Greshake, Oliver Tills, Manuela Truebano, Simon D. Rundle, Juraj Paule, Ingo Ebersberger, Markus Pfenninger

Tools & Resources

PhysiCell: an Open Source Physics-Based Cell Simulator for 3-D Multicellular Systems. Ahmadreza Ghaffarizadeh, Samuel H. Friedman, Shannon M. Mumenthaler,Paul Macklin

pathVar: a new method for pathway-based interpretation of gene expression variability. Laurence de Torrente, Samuel Zimmerman, Deanne Taylor, Yu Hasegawa, Christine A Wells, Jessica C Mar

MultiCellDS: a community-developed standard for curating microenvironment-dependent multicellular data.  Samuel H. Friedman, Alexander R.A. Anderson, David M. Bortz, Alexander G. Fletcher, Hermann B. Frieboes, Ahmadreza Ghaffarizadeh, David Robert Grimes, Andrea Hawkins-Daarud, VStefan Hoehme, Edwin F. Juarez, Carl Kesselman, Roeland Merks, Shannon M. Mumenthaler, Paul K. Newton, Kerri-Ann Norton, Rishi Rawat, Russell C. Rockne, Daniel Ruderman, Jacob Scott, Suzanne S. Sindi, Jessica L. Sparks, Kristin Swanson, David B. Agus, Paul Macklin

HI-C 2.0: AN OPTIMIZED HI-C PROCEDURE FOR HIGH-RESOLUTION GENOME-WIDE MAPPING OF CHROMOSOME CONFORMATION. Houda Belaghzal, Job Dekker, Johan H. Gibcus

The Image Data Resource: A Scalable Platform for Biological Image Data Access, Integration, and Dissemination. Eleanor Williams, Josh Moore, Simon W Li, Gabriella Rustici, Aleksandra Tarkowska, Anatole Chessel, Simone Leo, Balint Antal, Richard K Ferguson, Ugis Sarkans, Alvis Brazma, Rafael E Carazo-Salas, Jason Swedlow

SINCERITIES: Inferring gene regulatory networks from time-stamped single cell transcriptional expression profiles. Nan Papili Gao, Minhaz S.M. Ud-Dean, Rudiyanto Gunawan

Reducing mitochondrial reads in ATAC-seq using CRISPR/Cas9. Lindsey Montefiori, Liana Gonzales, Zijie Zhang, Yoav Gilad, Carole Ober, Gregory Crawford, Marcelo Nobrega, Noboru Jo Sakabe

SCODE: An efficient regulatory network inference algorithm from single-cell RNA-Seq during differentiation. Hirotaka Matsumoto, Hisanori Kiryu, Chikara Furusawa, Minoru S.H. Ko, Shigeru B.H. Ko, Norio Gouda, Tetsutaro Hayashi, Itoshi Nikaido

Scalable variational inference for super resolution microscopy. Ruoxi Sun, Evan Archer, Liam Paninski

Flowtrace: simple visualization of coherent structures in biological fluid flows. William Gilpin, Vivek N. Prakash, Manu Prakash

Tunable Extracellular Self-Assembly of Multi-Protein Conjugates from Bacillus subtilis. Charlie Gilbert, Mark Howarth, Colin Harwood, Tom Ellis

Multispot single-molecule FRET: high-throughput analysis of freely diffusing molecules. Antonino Ingargiola, Eitan Lerner, SangYoon Chung, Francesco Panzeri, Angelo Gulinatti, Ivan Rech, Massimo Ghioni, Shimon Weiss, Xavier Michalet

The Monarch Initiative: Insights across species reveal human disease mechanisms. Christopher Mungall,Julie McMurry, Sebastian Koehler, James Balhoff, Charles Borromeo, Matthew Brush, Seth Carbon, TOM CONLIN, Nathan Dunn, Mark Engelstad, Erin Foster, Jean-Philippe Gourdine, Julius Jacobsen, Daniel Keith, Bryan Laraway, Suzanna Lewis, Jeremy Nguyen Xuan, eKent Shefchek, Nicole Vasilevsky, Zhou Yuan, Nicole Washington, Harry Hochheiser,Tudor Groza, Damian Smedley, Peter Robinson, Melissa Haendel

Away from the bench

Ten simple rules for structuring papers. Konrad P Kording, Brett Mensh

Can paid reviews promote scientific quality and offer novel career perspectives for young scientists? Christian Wurzbacher, Hans-Peter Grossart, Erik Kristiansson, Henrik R Nilsson, Martin Unterseher

Starting from the end: what to do when restricted data is released. Marta Teperek, Rhys Morgan, Michelle Renee Ellefson,Danny Kingsley

Scientific data science and the case for Open Access. Gopal P Sarma

Why not…

How lizards fly: A novel type of wing in animals. J Maximilian Dehling

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The Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute is founded on the concept that deep understanding of stem cell biology will contribute to transforming future healthcare (http://www.stemcells.cam.ac.uk). In 2018 we will move into a new purpose built building adjacent to Addenbrooke’s Hospital and multiple research institutes – http://cambridge-biomedical.com/.

The Institute has openings for Group Leaders who will complement and synergise with our existing programmes. Areas of particular interest include:

i. The interface between physical, materials or engineering sciences and stem cell biology

ii. Cell and gene therapy

iii. Ageing of stem cells

Junior group leader candidates will have a minimum of 3 years post-doctoral experience, distinctive research achievements, and an original project proposal. Senior group leader candidates will be internationally recognised for independent high quality science and have an exceptional and well-founded research proposal.

The Institute offers a collegiate environment with excellent core facilities plus extensive opportunities to pursue basic and disease focussed studies. Successful candidates will be supported to obtain external personal fellowship and grant support within 1-2 years. Interim start-up packages may be available. Depending on experience, non-Clinicians can expect remuneration between £39,324 and £66,835.

To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/12123. This will take you to the role on the University’s Job Opportunities pages. There you will need to click on the ‘Apply online’ button and register an account with the University’s Web Recruitment System (if you have not already) and log in before completing the online application form.

Applicants should upload a curriculum vitae (max 3 pages, to include date of PhD and details of any career gaps if applicable) with contact details of 3 referees, and a 1-2 page outline of your research proposal, by  Sunday 29^th  January 2017.

Informal enquiries about the post are welcome via email to sci-administrator@stemcells.cam.ac.uk.

Interviews will be held in April 2017. Please quote reference PS10734 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity. The University has a responsibility to ensure that all employees are eligible to live and work in the UK. Benefits include generous maternity/ paternity leave, flexible working and funds for returning carers and other family-friendly schemes.

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