By Amie L. T. Romney and Jason E. Podrabsky from the Podrabsky Lab at The Center for Life in Extreme Environments at Portland State University

Environmentally-induced developmental plasticity provides an opportunity to explore one of the grand challenges of modern biology – identifying mechanisms that link genotype to phenotype. The annual killifish, Austrofundulus limnaeus is a particularly useful vertebrate system to address this question. Embryos of A. limnaeus are highly resistant to environmental extremes, and may in fact define the limits for vertebrate survival without oxygen. Yet, they remain highly responsive to environmental cues during development that can trigger a remarkable capacity for plasticity. Recently, we discovered that vitamin D₃ synthesis and signaling directly links environmental cues into the developmental program of this species, and supports their ability to develop along two alternative developmental trajectories. This work provides a framework for exploring the role of nuclear receptors as master regulators of developmental plasticity and life history transitions across all animal taxa.

Biology of A. limnaeus
A. limnaeus has adapted to life in a highly variable and often extreme environment. The ponds of its native habitat in Venezuela are ephemeral¹, and form during the warm rainy season. High spatial and temporal variation in rain events produces ponds that are transient and can undergo multiple cycles of drying and flooding even within a single season². When ponds dry, the entire adult and juvenile population dies, leaving only embryos to survive the dry periods³. Embryos can endure drought in a state of diapause for months while encased in the pond sediment under conditions that likely impose hypoxia/anoxia and severe desiccation stress^4-6 (Figure 1). Diapause is a state of metabolic and developmental arrest that is characterized in this species by a severely depressed metabolism and heart rate, suppressed rates of proteins synthesis, the use of anaerobic pathways to support metabolism even in the presence of oxygen, and the induction of mechanisms that reduce evaporative water loss⁷.

There are three stages of diapause (I, II and III) possible during development in annual killifishes. Entrance into diapause II involves an alternative phenotypic trajectory that is unique morphologically, physiologically, and biochemically^{8, 9}. Some embryos within the population bypass or “escape” diapause II and develop continuously toward hatching³, presumably completing their entire lifecycle within a single rainy season, while embryos that enter diapause II will have to wait for several months or perhaps years to hatch. Having mixed proportions of the diapause and escape phenotypes may provide an advantage for survival of the population in the face of unpredictable or fluctuating conditions. Because tolerance of extreme conditions is higher in diapausing embryos, there is a clear advantage for entering diapause II under times of extended drought.

Vitamin D is not for Diapause
The developmental phenotype of killifish is regulated by two factors: an age-related maternal effect, and the incubation environment of the embryo. Typically, younger females produce a high proportion of escape embryos and older females produce diapausing embryos. However, offspring from a single spawning event, even when incubated under identical conditions, can differ in developmental outcomes. While phenotype can initially be determined by maternal patterns, the embryonic environment can override this programming⁹. The strongest effectors are exposure of embryos to light and incubation temperature, and there is a critical window (between 10 and 20 pairs of somites) prior to the entry into diapause II when these environmental factors cause commitment to a given developmental trajectory.

We recently identified temperature-dependent vitamin D₃ signaling as a regulator of developmental phenotype in A. limnaeus¹⁰. When eggs from a single female are incubated at temperatures of 30˚C and 20˚C, embryos develop exclusively along escape and diapause trajectories, respectively, independent of maternal influences⁹. Under warmer conditions, embryos express a network of genes that code for enzymes responsible for synthesizing 1α, 25-dihydroxyvitamin D₃, the active form of vitamin D₃, and the signaling molecule that binds to the vitamin D receptor (VDR). Presumably, VDR binding to DNA response elements initiates a gene expression program that drives active growth and development along the escape trajectory (Figure 2).

Common knowledge of vitamin D₃ synthesis and signaling is based largely on studies in humans and other terrestrial mammals, and spurred by the discovery of the importance of vitamin D₃ in preventing rickets, a disease caused by perturbations in blood calcium homeostasis. Vitamin D₃ is not actually a vitamin, but is rather a highly potent hormone that, under the right conditions, can be synthesized by humans and many other species from the precursor molecule 7-dehydrocholesterol (7-DHC). In humans, exposure of 7-DHC in the skin to UV-B light and increased temperatures results in the production of vitamin D₃ (cholecalciferol)¹¹. Vitamin D₃ is then hydroxylated by two different enzymes to produce 1α, 25-dihydroxyvitamin D₃. In many systems it appears that formation of vitamin D₃ is a major limiting step in this synthetic pathway – thus linking seasonal changes in light and temperature to organismal levels of vitamin D₃. It important to note that some species of fish can synthesize vitamin D₃ using blue light and recent work suggests the potential for enzymatic conversion of 7-DHC to vitamin D₃-like compounds in mammals^{12, 13}.

Deep conservation for regulating life history decisions in animals
The VDR is a nuclear receptor (NR) – a transcription factor whose action is regulated by binding to specific molecules or ligands. Upon ligand binding, the VDR forms heterodimers with coactivating NRs such as the retinoid X receptor and the thyroid hormone receptor to drive cascades of gene transcription for calcium transport, hormone secretion, and cellular proliferation and differentiation¹⁴. The VDR is the vertebrate homolog of daf-12, a NR critical for regulating dauer dormancy – a state of developmental arrest similar in many ways to A. limnaeus diapause – in the nematode Caenorhabditis elegans^{15, 16}. It is well understood that environmental induction of insulin/IGF-1, TGFβ, and cGMP signaling pathways converge on DAF-12 to inhibit dauer formation and promote active growth, development, and reproduction¹⁵. Thus, it appears that regulation of developmental arrest and dormancy is regulated by homologous pathways in nematodes and fishes, suggesting a deeply conserved mechanism for integration of environmental signals into animal developmental programs.

Maternal-embryo conflict: checkpoints for phenotypic plasticity
The ecological significance of light and temperature in vitamin D₃ signaling and regulation of developmental trajectory is not fully understood in A. limnaeus or any other species of annual killifish. In their native habitat in the Maracaibo basin of Venezuela, embryos of A. limnaeus are exposed to a wide range of temperatures and may – especially during the dry season – be exposed to light. Thus, vitamin D₃ synthesis can provide a direct link between variations in the developmental environment and regulation of phenotype. However, developmental phenotype in A. limnaeus is regulated at two separate life stages: through maternal influences during oogenesis and later by the environmental conditions experienced by free-living developing embryos (Figure 3). Having two checkpoints that offer a regulatory capacity for determining developmental phenotype may offer a distinct survival advantage in the highly variable and often unpredictable seasonal ponds.

We hypothesize that maternal influences related to maternal age may help to integrate more reliable and predictable environmental conditions into the developmental program. Ecologically, this is logical because young females are usually found in newly formed ponds at the beginning of the season, and their early offspring have the greatest probability of completing the life cycle within a single rainy season. This may be especially important in ponds that experience multiple inundation and drying events during a single rainy season, allowing multiple generations or attempts at reproduction during a single season – a scenario that would be almost impossible if all embryos entered into diapause II. Maternal influences may also integrate other environmental factors that have yet to be explored in this system, such as food quality and quantity and social interactions.

Regulation of developmental phenotype during embryogenesis in a free-living embryo offers an opportunity to alter developmental outcomes in response to environmental cues that are inconsistent with maternal programming. Recent fieldwork suggests that embryos of annual killifishes remain in diapause I during the duration of the rainy season, and that development between diapause I and II occurs during the initial period of pond drying. Thus, the narrow window of development when temperature and light may affect development would allow for the embryo to “assess” environmental conditions when the ponds are drying and potentially alter developmental trajectory based on local environmental conditions. In this scenario, warm and moist conditions and/or exposure to light would result in active development while cool and dark conditions would favor entrance into diapause II. This mechanism could allow for embryos to respond to prevailing seasonal patterns in the environment, or to local microenvironmental cues. Perhaps embryos that are buried deep in the substrate remain cool and dark and enter into diapause II, while those in the upper layers experience warmer conditions with the chance for light exposure and thus develop along the escape trajectory. It is important to note that very little is known about the spawning behavior of annual killifishes, and it is possible that females may choose spawning sites, for instance in the shallow pond periphery, where the chances for exposure to higher temperatures and light are more likely. Thus, adding another layer of complexity to the potential for bet-hedging of developmental phenotype in this species.

Animals have evolved exquisite strategies to optimize developmental programs to prevailing environmental conditions to maximize growth, survival, and fitness. Here we have uncovered what appears to be a deeply conserved mechanism for integrating environmental cues into animal developmental programs with respect to entrance into developmental dormancy. This discovery suggests that many other developmental and life history transitions may be regulated in a similar manner. While it has been known for many years that nuclear receptors can be powerful regulators of phenotype, their role in developmental plasticity has received much less attention. We predict a major role for the VDR and other NRs in the regulation of other major vertebrate life history transitions such as smoltification in salmonids, metamorphosis in amphibians, and hibernation in small mammals.

1. Thomerson, J. and D. Taphorn, The annual killifishes of Venezuela part I: Maracaibo basin and coastal plain species, in Tropical Fish Hobbyist. 1992. p. 70-96.
2. Podrabsky, J.E., T. Hrbek, and S.C. Hand, Physical and chemical characteristics of ephemeral pond habitats in the Maracaibo basin and Llanos region of Venezuela. Hydrobiologia, 1998. 362:67-78. DOI: 10.1023/A:1003168704178.3. Wourms, J.P., The developmental biology of annual fishes III. Pre-embryonic and embryonic diapause of variable duration in the eggs of annual fishes. Journal of Experimental Zoology, 1972. 182:389-414. DOI: 10.1002/jez.1401820310.
4. Myers, G.S., Annual fishes. Aquarium Journal, 1952. 23:125-141.
5. Podrabsky, J.E., J.F. Carpenter, and S.C. Hand, Survival of water stress in annual fish embryos: dehydration avoidance and egg envelope amyloid fibers. American Journal of Physiology, 2001. 280:R123-R131.
6. Podrabsky, J.E., et al., Extreme anoxia tolerance in embryos of the annual killifish Austrofundulus limnaeus: Insights from a metabolomics analysis. Journal of Experimental Biology, 2007. 210:2253-2266. DOI: 10.1242/jeb.005116.
7. Podrabsky, J.E. and S.C. Hand, The bioenergetics of embryonic diapause in an annual killifish, Austrofundulus limnaeus. Journal of Experimental Biology, 1999. 202:2567-2580.
8. Podrabsky, J., A. Romney, and K. Culpepper, Alternative Developmental Pathways, in Annual Fishes. Life History Strategy, Diversity, and Evolution, N. Berois, G. García, and R. De Sá, Editors. 2016, CRC Press, Taylor & Francis: Boca Raton, FL USA. p. 63-73.
9. Podrabsky, J.E., I.D.F. Garrett, and Z.F. Kohl, Alternative developmental pathways associated with diapause regulated by temperature and maternal influences in embryos of the annual killifish Austrofundulus limnaeus. Journal of Experimental Biology, 2010. 213:3280-3288. DOI: 10.1242/jeb.045906.
10. Romney, A., et al., Temperature Dependent Vitamin D Signaling Regulates Developmental Trajectory Associated with Diapause in an Annual Killifish. Proceedings of the National Academy of Sciences of the United States of America, 2018. 115:12763-12768.
11. Holick, M.F., et al., Photosynthesis of previtamin D3 in human skin and the physiologic consequences. Science, 1980. 210:203-205.
12. Slominski, A.T., et al., Novel activities of CYP11A1 and their potential physiological significance. Journal of Steroid Biochemistry and Molecular Biology, 2015. 151:25-37.
13. Pierens, S. and D. Fraser, The origin and metabolism of vitamin D in rainbow trout. Journal of Steroid Biochemistry and Molecular Biology, 2015. 145:58-64.
14. Ramagopalan, S.V., et al., A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution. Genome Research, 2010. 20:1352-1360.
15. Fielenbach, N. and A. Antebi, C. elegans dauer formation and the molecular basis of plasticity. Genes and Development, 2008. 22:2149-65. DOI: 10.1101/gad.1701508.
16. Antebi, A., et al., Daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. Genes and Development, 2000. 14:1512-1527.

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This interview, the 54th in our series, was published in Development last year

In contrast to nerves in the central nervous system, peripheral nerves are highly regenerative following injury. Regeneration is critically dependent on Schwann cells, the main glial cell type of the peripheral nervous system, but whether an additional stem cell or progenitor population also contributes has been a matter of contention. A paper in Development now addresses this issue with a characterisation of Schwann cell behaviour in the homeostatic and regenerating mouse peripheral nerve. We caught up with first author and PhD student Salome Stierli, and her supervisor Alison Lloyd, Professor of Cell Biology at the MRC Laboratory for Molecular Cell Biology at University College London, to find out more about the story.

Alison, can you give us your scientific biography and the questions your lab is trying to answer?

AL I trained as a biochemist at University College London (UCL), before studying for my PhD with Chris Marshall and Alan Hall at the Institute of Cancer Research, also in London. To work with Chris and Alan was the best possible start to a career in science and they remained my mentors until their untimely deaths in 2015. After my PhD, I did a couple of post-docs in Strasbourg and at the Imperial Cancer Research Fund in London, interspersed with a three-year break during which I had a baby and worked as an IP administrator with the Ludwig Institute.

I returned to UCL to start my own laboratory at the MRC Laboratory for Molecular Cell Biology in 1999, and I have remained here ever since. Throughout my career, I have always been a cancer biologist, and intrigued by how we can stay ‘normal’ for so long (homeostasis), and what causes these controls to break down (cancer). While initially I started by studying oncogenic signalling pathways in cells, it became increasingly clear that to answer these questions required an understanding of cell signalling within the context of tissue biology.

The peripheral nerve has become our tissue of choice for these questions, and the biology of this tissue enables us to address many fundamental biological questions. Peripheral nerves mainly consist of neurons and glia (Schwann cells), and the behaviour of each cell type is controlled by interactions between them. Crucially, peripheral nerve is a regenerative tissue, and we can use it to understand the multicellular response allowing tissues to switch between normal and regenerative states, which has important implications for multiple aspects of tumourigenesis. We continue to ask questions about how cells talk to each other to create a tissue and reach a homeostatic state, how the tissue is reprogrammed to regenerate following injury, and how this is relevant to the processes of tumourigenesis.

And Salome, how did you come to join the Lloyd lab, and what drives your research?

SS I joined the Lloyd lab as graduate student fascinated by the biology of the nervous system. Prior to joining the Lloyd lab, I had been working on glioblastoma signalling in the group of Brian Hemmings in Basel, and ever since that time I have been highly interested in understanding the mechanisms that drive tumour formation within the nervous system. The extensive expertise of the Lloyd lab in understanding the mechanisms of peripheral nervous system (PNS) regeneration and tumourigenesis, and the lab’s use of tissue regeneration as a model for multiple aspects of tumourigenesis, provided me with the best environment to pursue my research interests.

Why has there been controversy over the existence and activity of stem cells in peripheral nerve regeneration?

SS & AL Adult stem cells exist in most tissues and have important roles in maintaining these tissues and/or in their response to injury. In peripheral nerve, mature adult Schwann cells were known to be able to re-enter the cell cycle, but to many it seemed likely that a stem cell population either ‘helped’ in the regeneration of this tissue and/or was the cell of origin for Schwann cell-derived tumours. Such a progenitor population exists in the central nervous system (CNS); for example, oligodendrocyte precursor cells produce oligodendrocytes (the corresponding cell to the PNS Schwann cell) throughout life. Previous studies have suggested that skin stem cells could contribute to the regenerative process, whereas other studies have suggested that adult Schwann cells retain a certain level of multipotency. However, most of these studies have been performed in vitro or in relatively non-physiological conditions.

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

SS & AL We show that peripheral nerve regeneration is underpinned by the proliferation of mature cells rather than the activation of a stem cell population. In particular, we demonstrate that although Schwann cells are highly quiescent, stable cells in the adult nerve, they all retain the capacity to dedifferentiate to a proliferating, migratory, progenitor-like Schwann cell following nerve injury. Moreover, these progenitor-like cells remain restricted to the Schwann cell lineage with both a tumorigenic mutation (loss of Nf1) and a conducive microenvironment required to enhance their plasticity.

Why do you think there are such distinct mechanisms for maintaining the myelinating cells of the PNS and CNS, cells that seem to do similar jobs in similar environments?

SS & AL We can only speculate upon this, but it is likely to reflect a trade-off between plasticity and stability: the CNS requires increased plasticity to myelinate new axons during processes like learning, for example, while the PNS requires stability to transmit signals from the CNS to tissues and organs. Moreover, although a continually proliferating progenitor population provides a rapid source for new myelination, it is also a pool susceptible to tumour development. This has been shown for other tissues, where the presence of proliferating stem or progenitor cells was correlated to enhanced susceptibility to tumourigenesis. Consistent with this, malignant tumours are more frequent in the CNS compared with the PNS, which perhaps reflects the presence of a more susceptible, proliferating progenitor population.

Does your work offer any clues for how we might enhance peripheral nerve regeneration in a clinical context?

SS & AL Yes, it suggests that stem cells are unlikely to be beneficial for improving peripheral nerve repair; encouraging the nerve’s ‘natural’ regenerative processes is likely to be the best approach. In addition, we suggest that the function of a regenerated tissue could be improved by clearing the matrix that accumulates but isn’t removed naturally following an injury.

When doing the research, did you have any particular result or ‘eureka moment’ that has stuck with you?

SS One of the most exciting moments in the lab was when we performed correlation light electron microscopy (CLEM) in order to clarify the plasticity of myelinating Schwann cells (mSCs) following nerve injury. The protocol took a while to perfect, but the moment we first managed to visualise the mSC-derived cells associated with small calibre axons was so rewarding that all the long hours and the effort was forgotten.

The moment we first managed to visualise the mSC-derived cells associated with small calibre axons was so rewarding

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

SS Yes of course: in general behind each scientific paper there are years of hard work that includes many failed experiments and some particularly frustrating moments. During this project, very frustrating moments involved spending many days preparing precious samples only to encounter technical issues with confocal microscopes. I have also experienced the difficulties of working with live animals, as this involves the impact of factors that are completely out of your own control.

So what next for you after this paper?

SS I am about to complete my PhD and I am thinking about doing a postdoc in in the field of cancer biology. Prior to that, I am planning to write a review on the plasticity of myelinating Schwann cells. I have not decided yet which lab I will join for my postdoctoral training, but in general I am very interested in extending my skills, for example by learning cutting-edge techniques such as in vivo imaging in order to elucidate the processes driving the early stages of tumour formation.

Where will this work take the Lloyd lab?

AL This work has increased our understanding of the cellular environment of the peripheral nerve, and has provided us with a tool-box to gain a greater understanding of how the environment of the nerve can be regenerative but also how it can provide a tumourigenic environment. We are currently exploring how the microenvironment of the nerve can both promote and inhibit tumourigenesis, and this work is a fundamental starting point to that question. This work has also shown that the reprogramming of a mature Schwann cell to a progenitor cell is a remarkably efficient process. We don’t understand how this works and that is an important question for the lab. In this paper, we have also characterised a new cell type in peripheral nerve, which we have called tactocytes. I want to know what they are doing!

Finally, let’s move outside the lab – what do you like to do in your spare time in London?

SS I must confess that in the last year of my PhD, spare time outside the lab has been fairly rare. However, when I got some time outside of the lab, I particularly enjoyed exploring the vibrant art and music scene in London and simply having a good conversation with friends over a nice meal. I also enjoy exploring the countryside outside of London and love to travel to new places.

AL I am a new grandma!

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This interview, the 53rd in our series, was published in Development last year

The ability to sense and respond to light is fundamental to plant development. As seedlings move from the soil to the air, a switch in developmental program occurs to promote light capture and autotrophic growth. A paper in Development now provides a molecular analysis of the proteins that regulate this transition in Arabidopsis. We caught up with first author and PhD student Vinh Ngoc Pham, and her supervisor Enamul Huq, Professor of Molecular Biosciences at The University of Texas at Austin, to find out more about the work.

Enamul, can you give us your scientific biography and the questions your lab is trying to answer?

EH I received BSc and MSc degrees in Biochemistry from the University of Dhaka, Bangladesh, in 1987 and 1988, respectively. As a graduate student in Thomas Hodges’ lab in Purdue University I worked on characterizing hypoxia-inducible gene expression in rice. I then did my post-doctoral research with Peter Quail at UC Berkeley, where I isolated and characterized phytochrome interacting factors (PIFs) in Arabidopsis.

I began my academic career as an Assistant Professor of Molecular Cell and Developmental Biology at The University of Texas at Austin in 2003, and am now a Professor of Molecular Biosciences. Research in my lab is focused on understanding how plants sense, interpret and respond to environmental light conditions that regulate almost every aspect of the life cycle, from seed germination to flowering time. Specifically, we focus on the red/far-red light photoreceptors (phytochromes) and their interacting PIFs.

And Vinh, how did you come to join the Huq lab and what drives your research?

VNP I have been fascinated by plants and how they respond to light signals since I was an undergraduate student. I did a student internship at POSTECH University in South Korea, working on PIFs. I decided to pursue my Master’s degree in POSTECH, and that was a great opportunity for me to learn the biology of light signalling. I first met Enamul during the International Plant Molecular Biology Conference in South Korea in 2012, and was interested in his research about PIF regulation. Being a Fellow of the Vietnam Education Foundation (VEF), an educational exchange program between Vietnam and the USA for PhD programs, I decided to apply to Enamul’s lab to continue my research in the light-signalling field.

What makes skoto-to-photomorophogenesis such a crucial developmental transition in a plant’s life?

VNP & EH Germinating seeds and young seedlings are very vulnerable, just like human babies at young ages. A proper transition from the dark-adapted developmental program called skotomorphogenesis to the light-adapted developmental program called photomorphogenesis is crucial for their survival. Skotomorphogenesis is defined by seedlings having long hypocotyls, appressed small cotyledons and an apical hook. This morphological pattern ensures the safe emergence of the seedlings, protecting their apical region in the subterranean darkness. Conversely, photomorphogenesis is defined by seedlings having short hypocotyls and open, expanded and green cotyledons that help plants capture maximum sunlight for photosynthetic energy production and autotrophic growth. Scientists have been using this transition to study light-signalling pathways for decades, and have isolated many mutants that mimic light-grown plants when grown in darkness. These are called constitutive photomorphogenic (cop) mutants, and have tremendously helped decipher mechanisms of light-signalling pathways.

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

VNP & EH In this paper, we provide multiple lines of evidence to explain why the cop1, spaQ and pifQ mutants display constitutive photomorphogenic phenotypes. Previously, it was shown that the so-called positively acting transcription factors were more abundant in cop1, spaQ and pifQ mutants compared with wild type, resulting in the cop phenotype. However, we now show that the cop phenotypes are not only due to a high abundance of the positively acting transcription factors, but also due to a reduced level of PIF protein levels. In addition, a high abundance of HFR1 in the cop1 and spamutants also reduces PIFs transcriptional activity. Strikingly, the gene expression signature of cop1 and spaQ overlaps with pifQ in the dark, with a preferential targeting of PIF direct target genes. All three activities are tightly linked to each other, contributing in concert to the cop phenotypes.

How do you think the COP1/SPA complex regulates PIF abundance and activity?

VNP & EH We think that the COP1/SPA complex regulates PIF abundance in both dark and light conditions. In the dark, HFR1, an atypical bHLH factor, is more abundant in the cop1 and spaQ mutants compared with wild type. HFR1 heterodimerizes with PIFs and induces degradation of this heterodimer through the COP1/SPA complex in darkness. In addition, HFR1 also sequesters PIFs from binding to DNA, thereby inhibiting PIF activity in darkness. In response to light, PIFs are phosphorylated in a phytochrome interaction-dependent manner. The phosphorylated forms of PIFs are then recruited by the COP1/SPA complex in a CUL4^COP1-SPA E3 Ubiquitin ligase complex for ubiquitylation and rapid degradation through the 26S proteasome pathway.

When doing the research, did you have any particular result or eureka moment that has stuck with you?

VNP In our lab, we do a lot of biochemistry and molecular genetics. At the beginning, I spent a lot of time studying genomic data analysis and enjoyed applying genomic data to the big picture of plant light-signalling pathways. Therefore, applying transcriptomic and gene expression tools in cop1, spaQ and pifQ mutants in this paper gave us an integrated view of how gene expression is regulated in light-signalling pathways. The interesting part of this paper was when we analysed the RNA-Seq data and figured out that more than 40% of PIF-regulated genes are significantly regulated by COP1 and SPA. After that we became more confident about our hypothesis of the cop phenotypes due to the regulation of PIF level and PIF transcriptional activity.

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

VNP I became frustrated many times working on the PIF degradation experiments. PIFs are degraded very quickly in the light so we have to do all the PIF protein experiments in the dark. That was not easy at the beginning but when I got used to it, I really enjoyed doing experiments in the dark room. It also gave me a chance to take an occasional nap!

It took us a very long time to generate the PIF5 overexpression line in the spaQ background, as this is a quadruple mutant and a tiny plant. spaQ mutants do not make a lot of seeds for the next generation, so we spent a lot of time genotyping and waiting for enough seeds to do all of our assays.

So what next for you after this paper?

VNP I am very excited about applying computational biology methods to study regulatory gene networks in light-signalling pathways. I hope this will be a great resource for other researchers and will provide a holistic view of the transcriptional regulatory mechanisms in Arabidopsis light-signalling pathways. After this project, I would like to find a postdoctoral position where I can apply and develop both my molecular genetics skills and computational biology to understand biological networks.

Where will this work take the Huq lab?

EH We are still focusing on the intersection between the COP1/SPA complex and PIFs. A simple Pubmed search on ‘COP1’ resulted in over 550 papers – including many from us – published in the last few years, and we really think they hold the key to light-signalling pathways in plants. On a molecular level, SPA proteins have kinase-like domains at their N terminus, but a kinase activity has not been demonstrated yet. If SPAs do function as protein kinases, the COP1/SPA complex might function as a unique cognate kinase-E3 Ubiquitin ligase complex for rapid phosphorylation and degradation of their substrates. There is so much more to be learned about these complexes and their biochemical functions in regulating plant development.

There is so much more to be learned about these complexes and their biochemical functions in regulating plant development

Finally, let’s move outside the lab – what do you like to do when you’re not working?

EH Austin is a lovely city. We really enjoy hiking and exploring the trails and parks nearby. In addition, Austin is the music capital of the world as well as a kind of second Silicon Valley with many high-tech companies established here. With increasing international population on campus as well as around the city, Austin has a variety of great food and culture throughout the year.

VNP When I have free time, I try to cook great food, and I think I am a good pastry chef too. I think doing science is like cooking, following new recipes (protocols) to come up with interesting new outcomes!

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The Company of Biologists (biologists.com) is looking to recruit an experienced Scientific Copy Editor to work across our portfolio of five life-science journals. This temporary position is expected to last for up to a year (starting March 2019).

The role entails copyediting articles to a high standard, compiling author corrections, overseeing the journal production process, and liaising with authors, academic editors, external production
suppliers and in-house staff to ensure that articles are published in a timely and professional manner.

Candidates should have a degree (ideally a PhD) in a relevant scientific area. Previous copyediting experience is essential. Additional requirements include excellent literacy skills, high attention to detail, a diplomatic communication style, good interpersonal and IT skills, a flexible approach and the ability to work to tight deadlines.

The position gives an experienced copy editor the opportunity to work on our highly successful life-science journals and offers an attractive salary and benefits. The position will be based in The Company of Biologists’ attractive modern offices on the outskirts of Cambridge, UK.

The Company of Biologists exists to support biologists and inspire advances in biology. At the heart of what we do are our five specialist journals – Development, Journal of Cell Science, Journal of Experimental Biology, Disease Models & Mechanisms and Biology Open – two of them fully open access. All are edited by expert researchers in the field, and all articles are subjected to rigorous peer review. We take great pride in the experience of our editorial team and
the quality of the work we publish. We believe that the profits from publishing the hard work of biologists should support scientific discovery and help develop future scientists. Our grants help support societies, meetings and individuals. Our workshops and meetings give the opportunity to network and collaborate.

Applicants should send a CV to recruitment@biologists.com, along with a covering letter that summarises their relevant experience, why they are enthusiastic about the role, and their current
salary.

All applications must be received by Monday 11 February.

Applicants must be eligible to work in the UK

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The Solana lab is looking for a postdoctoral computational researcher to work on single-cell transcriptomic and genomics of planarian stem cell differentiation. Our lab just started in Oxford Brookes University. We are currently three lab members but we will expand soon. We recently obtained funding from the MRC to expand our single-cell analysis of planarian stem cells.

Background

Single-cell analysis methods are revolutionizing the study of stem cells and development. The planarian Schmidtea mediterranea is a very promising model for stem cell biology thanks to its large number of stem cells. They continuously differentiate to all adult cell types and that enable its amazing regenerative capacities. We have previously used single-cell transcriptomics to study stem cell differentiation in planarians (see Plass, Solana et al. Science 2018). Combining clustering algorithms with graph mathematics and RNA metabolism information, we were able to reconstruct the differentiation lineage tree of planarian stem cells. Our methods, together with those of other groups analysing the developmental biology of Zebrafish, Xenopus and other models at the single-cell level, have been the Breakthrough of the Year 2018 by the Science Magazine.

Research

Future projects in the lab will use these methods and develop them further to study stem cells in planarians and other organisms. Planarians offer the advantage that the whole lineage tree of differentiation is present in just one stage, their adult. Therefore, we can study all differentiated cells, their progenitors and the stem cells all at once. We will use single-cell genomic methods to investigate the regulation of stem cell differentiation at the genomic and transcriptomic level. We will also use the same tools to study other planarian species to get insights into cell type evolution and the regulation of their differentiation. Finally, we will examine other regenerative species to establish the fundamental cellular mechanisms that underlie animal regeneration.

Application

For details about funding possibilities contact Dr. Jordi Solana jsolana[at]brookes.ac.uk

For suitability enquiries please include a CV and a brief motivation email.

To apply, please follow the link:

https://www.jobs.ac.uk/job/BPG192/postdoctoral-research-fellow-biological-and-medical-sciences

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The Turing Centre for Living Systems (CENTURI) wishes to attract talented PhD students to the Luminy campus (Marseille, France) and will fund up to 12 PhD fellowships to start in 2019, for three years. PhD students will work in an interdisciplinary life science environment, and have backgrounds in any of the following fields: cell or developmental biology, immunology, neurobiology, biophysics, theoretical physics, computer science, bioinformatics, applied mathematics, engineering. PhD projects must involve at least two research groups from different disciplines, to foster collaborations and interdisciplinarity.

Candidates can either apply to one of the advertised CENTURI projects or submit their own project, providing that they meet the application criteria and that their application is supported by at least one host lab.

Expected profile – selection criteria

Candidates must have, or expect to obtain a Master’s degree in biology, computer science, computational biology, mathematics, physics or engineering. Candidates will be evaluated on the following criteria:

• Academic achievements
• Past research experience (internships)
• Ability to work on a collaborative research project
• Ability to work in a multidisciplinary research environment
• Enthusiasm and communication skills

To see the list of PHD projects and to apply, please visit: http://centuri-livingsystems.org/recruitment

PhD duration: 3 years

Deadline for application: February 15, 2019

Interviews in Marseille (pre-selected candidates only): April 23 – 26, 2019

How to apply:

Students are required to apply on CENTURI’s website. Applications must include the following documents (compiled into a single PDF file):

• CV
• cover letter
• transcript of your MSc’s grades (M1 and M2 if available)

2 letters of recommendation must also be sent by your references at info@centuri-livingsystems.org.

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Identity and Diversity: Developmental Biology from Molecules to Cells to Organisms

Mt. Holyoke College, MA, USA

June 16th-20th, 2019 (GRS June 15th-16th)

https://www.grc.org/developmental-biology-conference/2019/

The 2019 Gordon Conference on Developmental Biology will present the most recent, cutting-edge research in the field. In keeping with this year’s theme of Identity and Diversity: Developmental Biology from Molecules to Cells to Organisms, we will have nine sessions of oral presentations covering cell identity and robustness in the era of single-cell ‘omics, developmental time, chromatin and epigenetic influences on cell identity, dynamic imaging (and imaging dynamics), new concepts of pattern, metabolism and growth control, developmental robustness in noisy systems and will feature a number of investigators working towards in vitro precision in vivo. This year we will also pay tribute to 50 years of “Positional Information”, recognizing the 1969 landmark paper and the work by Lewis Wolpert and others that led to this conceptual synthesis.

Abstracts due March 15th for talk consideration

2019 dev bio GRS_GRC poster

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Genetics Unzipped – a new fortnightly podcast from the UK Genetics Society – has launched ahead of the society’s centenary celebrations throughout 2019.

Presented by award-winning science writer and former Naked Genetics/Naked Scientists podcast host Kat Arney and produced by First Create The Media, Genetics Unzipped will bring you a wide range of stories from the world of genetics, genomics and DNA.

Listeners can expect to hear interviews with experts from around the world, all the latest science news, and a special centenary series celebrating 100 ideas in genetics.

The first full episode is a behind-the-scenes peek at the iconic 2018 Royal Institution Christmas Lectures on the theme ‘Who am I?’, presented by Professors Alice Roberts and Aoife McLysaght, alongside professional pyromaniac and demonstration expert Fran Scott.

The second episode weaves together stories and sounds to explore the deadly DNA that causes Huntington’s disease, find out how a chicken virus managed to win three Nobel prizes, and discovers the silky science of spidergoats.

Founded in 1919, the Genetics Society is one of the oldest learned societies in the world dedicated to supporting and promoting the research, teaching and application of genetics. The Society is a registered charity whose membership includes over 1900 of the UK’s active professional geneticists, including teachers, researchers and students, and is open to anyone with an interest in genetic research or teaching, or in the practical breeding of plants and animals.

Kat Arney is an award-winning science writer, public speaker and broadcaster, and author of the popular genetics books Herding Hemingway’s Cats and How to Code a Human. She co-presented the ground-breaking Naked Scientists BBC radio show and podcast for 15 years, produced and presented the Naked Genetics podcast for 6 years, and has fronted numerous BBC radio 4 science programmes including the comedy factual series Did the Victorians Ruin the World?

Kat founded the communications and media consultancy company First Create the Media in 2018 to enable organisations and companies to find and tell compelling stories about science.

Email podcast@geneticsunzipped.com to get in touch with questions and suggestions for future topics and guests.

Genetics Unzipped is online at Geneticsunzipped.com. Subscribe for free from Apple Podcasts, Google Play, Stitcher, Blubrry, TuneIn, Spotify, Spreaker and all good podcast apps.

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