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An interview with Cheryll Tickle

Posted by , on 5 April 2016

This interview first featured in Development.

 

Cheryll Tickle is an Emeritus Professor at the University of Bath, UK. She dedicated her long research career mainly to the study of limb development in the chick, and has received numerous awards for her contributions to science, including being elected a Fellow of The Royal Society and receiving a CBE from the Queen. This year the British Society for Developmental Biology (BSDB) has created a new award in her honour, the Cheryll Tickle Medal, to be awarded to a mid-career, female scientist for outstanding achievements in the field. We asked Cheryll what this award means to her and how science has changed during her career.

 

Cheryll TickleHow did you first become interested in developmental biology and why did you decide to study limb development?

As an undergraduate I was most interested in cell biology. I was excited by the idea of understanding how cells behave and how they build tissues in embryos. At the time, developmental biology was usually called embryology, and it was the only subject that seemed totally mysterious and unfathomable: there were no general principles that I could get hold of. So I did a PhD in cell biology in the lab of Adam Curtis, who had just become Professor at Glasgow in the first Department of Cell Biology in the UK. I studied a phenomenon known as ‘cell sorting’, which was very exciting in the 1960s. Malcolm Steinberg, building on earlier work in amphibians, had shown that if you disaggregated cells from the various tissues of the embryonic chick and mixed them together, they would sort themselves out so that cells of the same type preferentially adhered to each other. It was not clear whether a similar process happened in embryos, but it was one possible way by which you could build patterns of differentiated cells.

One of the cell types I used during my PhD in Glasgow was limb bud cells. In the limb you could imagine how cells might get committed at random to become cartilage cells and then ‘sort out’ to the centre of the limb. At that time Donald Ede, who was based in Edinburgh, used to come over to Glasgow with his PhD student Oliver Flint to use Adam’s Couette viscometer to measure cell adhesiveness. Donald was looking at limb bud development in normal chick embryos and in a mutant called talpid3, which was polydactylous and had various defects. His research further reinforced my idea to study limb development and ignited an interest in the mutant. After Donald retired, Dave Burt at the Roslin Institute took on the maintenance of the talpid3 mutant flock. We continued to study it and eventually identified the gene responsible for the phenotype and showed that it is a ciliopathy. Very recently, several groups have identified mutations in the talpid3 gene in patients with Joubert syndrome.

After my PhD I was awarded a NATO fellowship to do a postdoc in America, and I worked with John Trinkaus in Yale for 2 years, on aggregation of cell lines and cell behaviour in early fish embryo development. However, when I went for my fellowship interview I was asked what I would eventually like to work on. When I said ‘limb development’, the person who interviewed me said that he wouldn’t recommend that because everything was already known!

 

Did any mentors play an important role in your career?

There were three important mentors in my career. I was very fortunate with my PhD supervisor Adam Curtis, my first postdoctoral supervisor John Trinkaus and then of course with Lewis Wolpert, with whom I did a second postdoc funded by the MRC. They all supported me. I was recently asked why it was that a group of successful women embryologists came through from the 1960s and 1970s. I think in my case it was partially the attitude of the men I worked with. They allowed me the freedom to develop and did not put me down.

Another person that was very influential was Bruce Alberts, who I got to work with when he did a sabbatical in the Wolpert lab. He came armed with all these pots of beads and we started using the beads as carriers for applying chemicals to the limb bud. This technique is widely used now, but it was really being developed at the time. We used it to apply retinoic acid to the wing bud. Brigid Hogan was also very supportive during my early career when she was in the UK. Even though I wasn’t in the mouse field, she was supportive, encouraging me to apply for grants and so on.

 

How do you think that science has changed over the years in which you have been a researcher?

I think people tend to forget that in the 1960s and 1970s there was a lot of emphasis on cell biology, within the confines of what was possible. Quite a lot of the work I did was looking at cells in the limb, their morphology, whether they had gap junctions or not, etc. There were also quite a lot of productive interactions between people in different fields, particularly with mathematicians. During my PhD I collaborated with a statistician, Rob Elton, and we carried out a nearest neighbour analysis to quantitate the degree of sorting out in the aggregates that I had made. Computer modelling was also being used. Donald Ede had made some computer models of limb development, and I believe the computer that he used took up an entire room! These approaches bringing cell biology and/or mathematical modelling to bear on problems in embryonic development are now very much at the forefront of the field. Since my early work on limb development there have been two revolutions: being able to understand the genetic basis of development and the ability to do genome-wide analysis.

When I was carrying out my PhD, there were not so many people doing science, and the funding was easier to obtain. There wasn’t the level of competitiveness that you can see now, although it was very competitive in some areas! We seemed to have a lot more time to think and to ‘undertake scholarship’, such as studying primary papers in detail rather than just reading a review.

 

What do you think are the exciting scientific questions at the moment?

I think real progress is being made in the area of evo-devo, particularly in this new age of genomics. We are on the brink of learning a lot. There will be a huge amount of data, and for a while it will be very confusing. A little like the Hox gene clusters when they were first discovered. Eventually though it will all become clear. I think in general that developmental biology has not yet reaped the full rewards of the genomic age.

 

You are now an Emeritus Professor at Bath University. Do you miss doing science?

I really enjoyed doing science. When you discover something there is a real buzz. After a seminar in Switzerland, a member of the audience said that he had enjoyed hearing all about my tedious experiments! But of course I didn’t find them tedious. Doing experiments on chick embryos, cutting bits out, grafting them, observing them develop was always fascinating. So yes, I miss it a lot. No one gives you advice on how to finish your research career! But I am still very busy writing reviews, sitting on committees, and so on.

 

Over the years you have received many awards, including being elected a fellow of The Royal Society and being the first awardee of the Waddington Medal. What do these awards mean to you?

Receiving these awards is a bit overwhelming, but of course very nice. I remember that when I got the letter about the Waddington Medal I couldn’t believe it! Being a fellow of The Royal Society has been very positive. The Society is very supportive and you have the opportunity to meet people working on different areas of science, which is very interesting. Later on I also became a Royal Society Professor, so the Society directly supported my research, for which of course I am extremely grateful.

I think I received these awards because I was in the right place at the right time. I was lucky in my choice of research field and to work so closely with Lewis Wolpert for many years. The other important thing was the large number of collaborations I established with outstanding scientists in the field. I could combine my expertise with that of people like Denis Duboule and Gail Martin, working with Juan-Carlos Izpisua-Belmonte and Lee Niswander who were doing postdocs in their respective labs at that time. At UCL, I also worked with Anne Warner and Jon Clarke. By pooling our expertise, we were able to do a lot more than I would have been able to do on my own. And of course I had fantastic undergraduates, PhD students and postdocs. I feel that these awards were not just for me but for the whole enterprise.

 

This year the BSDB created a new award in your honour, the Cheryll Tickle Medal, which will be awarded to Abigail Tucker from King’s College London. What does it mean for you to have a medal named after you?

It is very humbling and a huge honour. I am actually going to present the award to Abigail. I was not involved in the selection of the winner, but I think Abigail is a very worthy recipient. I am very familiar with her work, in particular on how teeth are positioned within the jaw, which very much mirrors some of the work I did on the limb. It is research of fundamental importance, not just for our understanding of tooth development but also more generally.

 

This medal is awarded to a mid-career, female scientist for her outstanding achievements in the field of developmental biology. Do you think that there is the need for awards that specifically recognise the contributions of women in science?

The Chair of the BSDB, Ottoline Leyser, wrote in a recent society newsletter that all young scientists need encouragement and support, both men and women. However, because there is such a huge attrition in the number of women who go on to embark upon a scientific career, we need to celebrate the success of women and what they achieve. I used to feel that you could sum up the situation of women in science by saying that they are generally undervalued, overlooked and ignored. Fortunately things are changing – although it has been very slow.

There are many types of barriers for women in research. Having children is obviously a big barrier, but not being encouraged, especially if you are in a total male environment, can be a bit demoralising. While I was supported by my mentor, during my PhD in Glasgow I was the only female PhD student in the department. But when I went to Yale there were lots of women students around, and that made a quite a difference. I have tried to encourage other women, but maybe I have not been highly visible. I think that if every woman did something on a personal level we could easily conquer a lot of these difficulties. But of course we need to support our male colleagues as well, particularly at the beginning of their careers.

 

You said before (in an article in Nature) that current PhD students are not allowed as much freedom or to make as many mistakes as you did during your graduate training. Why do you think this is?

I think this is related to supervisors being too hands-on. I personally think that students should have more chances to make mistakes. In order to learn how to skate you need to fall over, and it is the same with science. You need to make some gaffes and learn from them. However, it is so competitive to get grants that there is increasing pressure to get results and not waste money. There is also more emphasis on training in narrow areas, rather than encouraging creativity. You are constrained to be in a particular way and receive particular kinds of training. It is all a bit too prescribed.

 

What is your advice for young scientists?

My advice would be to study something that you are really interested in. That is the most important thing. You are going to have to work extremely hard, and there will be quite a lot of lows as well as highs. It doesn’t really matter what the topic is, but it must be personally extremely interesting. I think a key attribute of a successful scientist is doggedness. Also, I would advise you to find people with whom you can work and share expertise. That is the way to make real progress.

 

You have been a director of The Company of Biologists for several years. How do you see the role of The Company of Biologists in the scientific community?

The Company of Biologists is a charity and not-for-profit publishing company, originally created in 1925 by the zoologist George Parker Bidder III to rescue the British Journal of Experimental Biology, which was failing. It now publishes a portfolio of journals, including Development, and has the aim of supporting research across all branches of biology, including the developmental biology field. I think The Company does not receive enough recognition for what it does. It gives huge amounts of money to the BSDB – both block grants to support its meetings but also travel grants. The Company of Biologists also awards its own travel grants and runs workshops. Sometimes you see a meeting that says ‘supported by The Company of Biologists’ along with many other sponsors, but people don’t really realise how much The Company gives to the field.

 

What would people be surprised to find out about you?

You could say that I have shared a stage with Bob Dylan. I was awarded an honorary degree from St Andrews University at the same time as Bob Dylan. There was an article in the New Musical Express that had a picture of me standing across the room from him, looking very pleased. One of my ex-students, Sarah Wedden, said that my street cred went up in the eyes of her teenage son!

 

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In Development this week (Vol. 143, Issue 7)

Posted by , on 5 April 2016

Here are the highlights from the current issue of Development:

 

TUBB5 analysis yields insights into microcephaly

DEV1126Mutations affecting tubulin genes have been implicated in a range of human neurological disorders but very little is known about the cellular mechanisms that underlie these disorders. Now, on p. 1126, David Keays and co-workers examine how a mutation in the murine homologue of TUBB5 leads to a disease phenotype. Using two new mouse models – a conditional Tubb5 E401K knock-in (which mimics a human mutation) and a conditional knockout – they reveal that Tubb5 perturbation causes a decrease in brain size in mice, mimicking the microcephaly phenotype described in patients with TUBB5 mutations. Although the laminar structure of the cortex is largely maintained in mutants, a loss of upper neuronal layers is seen. The authors further reveal that Tubb5 perturbation causes defects in mitotic progression that lead to massive apoptosis in the brain; in line with this, increased levels of the apoptotic driver p53 are observed. Finally, the researchers note that ectopic progenitors and spindle orientation defects are observed in Tubb5 E401K mutants but not knockout mice, suggesting that the E401K mutation acts via a complex mechanism. Together, these results provide key insights into the pathology underlying tubulin-associated diseases.

 

A new look for the tumour protein Tctp

Tctp is an evolutionarily conserved protein that has been implicated in cell growth and cancer. Transcripts encoding Tctp are known to be enriched within the axonal compartment of many neurons but how they function in this context is unclear. Here, motivated by the parallels between axon growth and cancer cell invasion, Christine Holt and colleagues investigate the role of Tctp in the Xenopus visual system (p. 1134). They first report that Tctp is expressed throughout the retina, including in retinal ganglion cell (RGC) axons. Using morpholino-mediated knockdown, the researchers reveal that Tctp is required for establishing correct axonal projections in the retina; RGC axons in morphants are shorter and grow in a dispersed fashion as a result of impaired axon extension. Tctp-depleted axons also exhibit a reduction in mitochondrial density and compromised axonal mitochondrial function. Finally, the authors demonstrate that axonal Tctp interacts with Bcl2-related myeloid cell leukaemia 1 (Mcl1) and that its pro-survival activity is required for normal axon development. In summary, these findings highlight a novel function for Tctp, suggesting that it supports axon development in the visual system via regulation of pro-survival signalling and axonal mitochondrial homeostasis.

 

Growth patterns during liver development

ImpressionThe liver is a vital organ, and understanding how it develops can provide key insights into liver disorders and regeneration. Here, Mary Weiss, Margaret Buckingham and colleagues use a retrospective clonal approach to provide an in-depth analysis of cell behaviour during liver development in mice (p. 1149). Using an Hnf4a/laacZ transgene, which produces β-galactosidase in cells in which a rare recombination event generates a functional lacZ reporter when the liver gene Hnf4a is expressed, two types of clone are identified. The first type, of which there are many, exhibits a limited number of cell divisions and is calculated to arise between E8.5 and E13.5, during a rapid growth phase. The second type, termed a ‘mega-clone’, is larger and is thought to arise from multipotent founder cells at an earlier stage; these generate descendants that also contribute to the pancreas and intestine. The authors note that clonally-related cells form distinct spots or stripes, rather than being dispersed, suggesting that growth is orientated and cohesive. Finally, they reveal that some mega-clones populate just one side of the liver, indicating the existence of a left-right chirality that most likely occurs after liver fate has been established. These observations yield novel insights into the cell behaviours that underlie liver morphogenesis and contribute to liver function.

 

PLUS…

 

Lineage specification in the mouse preimplantation embryo

DEV1063Chazaud and Yamanaka discuss recent advances in live imaging, computational modelling and single cell analyses that provide insights into how the first three cell lineages of the mouse embryo are generated.

 

DEV1075Unlocking the neurogenic potential of astrocytes in different brain regions

Magnusson and Frisén discuss the extent to which astrocytes in different brain regions can behave as neural stem cells, and the molecular and environmental factors that either promote or repress such activity.

 

Interviews with Cheryll Tickle and Abigail Tucker

This year the British Society for Developmental Biology created a new award, the Cheryll Tickle medal, to recognise the outstanding achievements of a female scientist in the field. In this issue we feature an  interview with Cheryll Tickle, after whom the medal is named, and with its first winner, craniofacial researcher Abigail Tucker.

 

Cheryll and Abigail

 

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Categories: Research

This month on the Node- March 2016

Posted by , on 1 April 2016

 

Focus on organoids

MelissaFollowing Development’s call for papers for their upcoming Special Issue on Organoids, we featured an interview with their guest editor Melissa Little, discussing her career and research on kidney development and organoids. Our question of the month focused specifically on brain organoids and the ethical issues involved. You can share your thoughts by leaving a comment here!

 

 

Research

Wolpert cropped – Liangyu discussed how he adapted the auxin-inducible degradation system to C. elegans, providing a new tool for conditional protein depletion in the worm.

– Our latest forgotten classic was a 1967 paper by Tryggve Gustafsson and Lewis Wolpert, where the careful observation of sea urchin development is the starting point to discover the principles governing morphogenesis.

 

 

bat sqauredAlso on the Node

– The life of a bat researcher is an exciting one, and includes trips to exotic locations. Find out more in ‘A day in the life of a bat lab‘!

– Ever wanted to influence the way science is portrayed in the movies? Pablo writes about his experience providing scientific advice to a film director.

– A scientific thriller- Katherine reviewed the book ‘Raw data‘, a novel on scientific misconduct.

– You had the chance to vote for you favourite movie from the 2014 Woods Hole Embryology Course, and this amazing video of a Drosophila embryo imaged in 7 channels was the big winner!

– And we remembered theoretical developmental biologist Hans Meinhardt, who recently passed away.

Hans Meinhardt_2011_08c

 

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Categories: Highlights

Woods Hole images 2014 round 2- the winner

Posted by , on 30 March 2016

The results are out! The winner of this year’s movie round from the 2014 Woods Hole Embryology course is… the Drosophila embryo imaged in 7 channels!

 

Here are the full results:

  • Fly embryo (Dorso-Ventral Split): 29
  • Fly embryo (Sections): 32
  • Fly Eye Disk: 10
  • Fly Embryo (7 channels): 76

 

 

Many congratulations to Connie Rich (University of Cambridge, UK), who made this video at the 2014 MBL Embryology Course. Connie’s video will feature on the homepage of Development and this frame will feature in the cover of a coming issue of the journal!

The other great videos that featured in this round were by Shane Jinson and Amber Famiglietti (dorso-ventral split), Carolyn Kaufman (embryo sections) and Jiajie Xu (eye disk).

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Postdoctoral Scientist – Genetic and Epigenetic Mechanisms of Aging

Posted by , on 29 March 2016

Closing Date: 15 March 2021

Marine Biological Laboratory | Woods Hole, MA | Salary commensurate with experience and qualifications

A postdoctoral research position is available at the Marine Biological Laboratory, in the laboratory of Dr. Kristin Gribble. The MBL is a premier venue for scientific discovery, attracting the world’s leading scientists and students for more than 125 years (http://www.mbl.edu/mbl-facts/). Qualified applicants will have the opportunity to study the molecular genetic and epigenetic mechanisms of aging in a unique and robust experimental invertebrate model system, with a specific focus on the mechanisms of maternal effects influencing offspring health and lifespan (Aging Cell 13:623 2014). This NIH-funded, multidisciplinary research program uses state-of-the-art molecular, genetic, biochemical, and phenotypic approaches to elucidate the fundamental mechanism of transgenerational epigenetic inheritance. The Gribble laboratory is positioned in a rich and diverse research environment amongst a number of vibrant investigators, students and postdoctoral fellows pursuing related genetic questions at the MBL.

Applicants should posses a Ph.D. and/or M.D. in molecular biology, cell biology, biochemistry, genetics, bioinformatics, or a related field. The ideal candidate will have a record of scientific rigor, productivity, and creativity; the ability to work both independently and as part of a team; and a strong publication record. Excellent oral and written communication skills are required. Highly motivated individuals with experience in other model systems and a background in biochemistry, cell/molecular biology, epigenetics, and/or bioinformatics are encouraged to apply.

Qualified applicants must apply for this position via the Marine Biological Laboratory careers website, mbl.simplehire.com/postings/3195. Please submit: (1) A cover letter describing your research goals and motivation for joining the lab; (2) a CV; (3) a 1-2 page research statement; and (4) contact information for three references.

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Categories: Jobs

Obituary: Hans Meinhardt (1938-2016)

Posted by , on 29 March 2016

This obituary first appeared in Development.

 

Patrick Müller and Christiane Nüsslein-Volhard reflect on the life and career of their colleague Hans Meinhardt.

 

Hans Meinhardt_2011_08cHans Meinhardt, a pioneer in the field of theoretical biology, died on 11 February 2016 in Tübingen. He made numerous important contributions to developmental biology by spearheading the use of mathematical models to investigate the logic of patterning in complex biological systems. His work expanded our understanding of the mechanisms behind diverse biological processes, from the generation of patterns on sea shells to the evolution of the brain.

Meinhardt grew up in the German Democratic Republic. His family fled to West Germany before the Wall was built. He studied physics at the University of Cologne and received his PhD in 1966. As a postdoc at the European High Energy Laboratory (CERN) in Geneva he gained expertise in computer-based modeling, but over time became more interested in biological processes and decided to move into the emerging field of molecular biology.

In 1969, Meinhardt joined the group of Alfred Gierer at the Max Planck Institute for Virus Research in Tübingen, Germany (which has since become the Max Planck Institute for Developmental Biology). Gierer, a physicist by training, and famous for the demonstration that RNA, not only DNA, could be the genetic material (Gierer and Schramm, 1956), was looking for new challenges in developmental biology. He had started a research group to study the miraculous regenerative capabilities of Hydra, which can self-organize perfect animals even after complete dissociation. Meinhardt’s initial project in Gierer’s department was purely experimental, isolating chromosomal proteins from cow blood cells. Meinhardt was convinced that this could be accomplished without using an ice bucket, arguing as a theoretician that the proteins should be stable at room temperature because they are also stable in living warm-blooded cows. However, discouraged by many wet lab failures, he looked for theoretical rather than experimental challenges.

Stimulated after a seminar by Günter Gerisch (a group leader at the newly founded Friedrich Miescher Laboratory) on oscillations and chemotaxis in the slime mold Dictyostelium, Meinhardt considered applying his expertise in computer modeling to simulate the aggregation of Dictyostelium. Gierer was intrigued by the thought of applying computational methods to developmental biology problems, but suggested that Meinhardt instead use this approach to develop a theory explaining the surprising regenerative capabilities of Hydra. This idea was inspired by two major influences. First, Magoroh Maruyama had demonstrated the importance of positive feedback – selfenhancement – that could dramatically amplify small deviations from initial conditions in diverse processes, from morphogenesis to economy (Maruyama, 1963). Second, neurophysiological work in the neighboring Max Planck Institute for Biological Cybernetics showed that contrast enhancement in the visual system is achieved by a local activation from a stimulus together with an inhibitory effect on surrounding areas of the retina, a mechanism termed lateral inhibition (Kirschfeld and Reichardt, 1964). The synthesis of these two concepts of local self-enhancement and lateral inhibition led Meinhardt and Gierer to formulate a theory explaining the emergence of polarity and pattern from near-uniform states.

Meinhardt and Gierer hypothesized that patterning could be mediated by a short-range activator with strong self-enhancing capabilities, coupled to an inhibitor of longer range that suppressed the expansion of the activator in the surrounding areas. Meinhardt then performed computer simulations to test whether their hypothesis could explain experimental observations. In the 1970s, no biological institute had a computer, so the numerical simulations had to be done using punch cards on a Hollerith machine at the computer center in the University of Tübingen. Much of the theory was based on Meinhardt’s remarkable intuition, which made the tedious computations feasible. Their famous theory of biological pattern formation was published in Kybernetik (Gierer and Meinhardt, 1972), followed by a paper on applications in the Journal of Cell Science (Meinhardt and Gierer, 1974). Although the theory was driven by the experimental work on Hydra, it also provided an important general recipe for self-organization. Strikingly, even in the absence of specific molecular data these models correctly predicted the behavior of several biological systems (Meinhardt, 1982; Meinhardt and Gierer, 2000).

Meinhardt and Gierer’s work is often regarded as equivalent to the earlier work of Alan Turing (Turing, 1952). However, they were not aware of Turing’s paper at the time of submission (Meinhardt, 2006a, 2008; Roth, 2011), and in fact the Meinhardt–Gierer model provided three important advances that were missing in Turing’s work. First, the fundamental concept of local self-enhancement and long-range inhibition, although inherent in Turing’s equations (Gierer, 1981), was not explicitly described in Turing’s paper. Strikingly, Meinhardt and Gierer had also intuitively found the only two possible realizations of self-organizing systems with two components: the activator/inhibitor system and the substratedepletion model (Murray, 2003). Second, Meinhardt and Gierer incorporated realistic pre-patterns that are often found in developing systems – the ‘source density’ – which provides the competence for autocatalysis. Turing’s model instead focused purely on selforganizing mechanisms in a homogenous field of cells. Third, using realistic Michaelis–Menten-based kinetics combined with the source density, the Meinhardt–Gierer models achieved robust and highly reproducible patterns that also scale with tissue size. This was possible because Meinhardt and Gierer introduced saturation kinetics and non-linear terms for the autocatalysis as opposed to Turing, whose models with linear kinetics have a fixed length scale (Roth, 2011). The molecular implementation of the Meinhardt– Gierer models was not strictly specified. Diffusion and degradation of molecules was the simplest way to implement short-range activation and long-range inhibition in the models, but Gierer and Meinhardt also considered other transport and inhibition mechanisms (Gierer, 1981).

In the mid-1980s, Meinhardt proposed models for Drosophila segmentation based on the discovery of mutations affecting segmentation in very specific ways (Nüsslein-Volhard and Wieschaus, 1980). He proposed, using simple logic, that periodic structures such as segments require at least three states to form unambiguous segment borders, not two states as had been previously assumed (Meinhardt, 1984, 1985, 1986). The molecular basis of the genes involved was not yet clear at the time, but the basic idea was to make stripes by assuming cooperation between neighboring cells with mutually exclusive states. Meinhardt’s attempts at modeling embryonic axis formation in Drosophila by self-organizing gradients failed, however, because Drosophila embryogenesis is strongly influenced by pre-patterns of localized maternal determinants and a transmission of this information by complex gene cascades (Akam, 1989; St. Johnston and Nüsslein-Volhard, 1992).

In the 1980s, Meinhardt had key insights into insect and vertebrate appendage development and regeneration (Meinhardt, 1980, 1983a,b). At the time, appendage patterning was explained by the ‘polar coordinate’ model (French et al., 1976). This theory proposed abstract circumferential positional values and complicated rules to explain regeneration experiments, but it was hard to envision how this could be implemented on a molecular level. Meinhardt instead postulated a much simpler and more elegant model, in which the intersection of three compartments could serve as an organizing center for the production of new peaks and subsequent appendage patterning. The theory was initially highly controversial; indeed, three journals rejected his manuscript describing this key insight before it was published in Developmental Biology (Meinhardt, 1983b). However, strong experimental support for this model was subsequently found (Vincent and Lawrence, 1994).

Together with his student, Martin Klingler, Meinhardt developed another breakthrough theory on the patterning of sea shells (Meinhardt, 1984; Meinhardt and Klingler, 1987). The inspiration came when he ordered spaghetti frutti di mare in an Italian restaurant in 1980 and realized that the patterns on the shells on his plate could arise from a self-organizing system. One day, he came into the lab with an excerpt of Doktor Faustus by Thomas Mann. He cited one of the protagonists lamenting on how difficult, if not impossible, it was to ever understand the complicated patterns on cone snails. But Meinhardt had found a general mechanism of how it might work. He published his findings in his classic book The Algorithmic Beauty of Sea Shells, which also supplies the source code that enables readers to reproduce and extend computer simulations of these and other biological patterns (Meinhardt, 1995).

Meinhardt worked on numerous other processes, from bacterial patterning to chemo- and phyllotaxis (Meinhardt et al., 1998, 1999; Meinhardt and de Boer, 2001). He also had a keen interest in comparative aspects of patterning systems, was driven to understand how different organisms solved similar tasks differently throughout evolution, and proposed that an ancestral body pattern evolved into the brain and heart of higher organisms (Meinhardt, 2002).

After his retirement in 2003, Meinhardt continued to work enthusiastically on his projects, publishing more than 20 papers. Unusually for modern times, he published most of his papers as the sole author. His most fruitful collaboration was with Alfred Gierer, with whom he also shared a life-long friendship. Meinhardt’s last publication dealt with the Spemann organizer, developing a unified theory of bone morphogenetic protein signaling and dorsoventral patterning and its relationship with anterior-posterior patterning in different organisms (Meinhardt, 2006b, 2015), but his latest work on planarian regeneration remains unfinished.

Meinhardt was known for riding his bicycle up the large hill to the Max Planck Institute every day, even after he retired. He was an ardent traveler and loved the desert, but was similarly fascinated by the local nature around him, discovering new facets in the old and gaining inspiration for his scientific questions. Much of his work was based on intuition that he then tested with computer simulations. His goal was to find organizing principles, to understand the logic of patterning systems despite apparent complexity, and to develop minimal models with predictive power.

Hans Meinhardt was a happy and dedicated scientist. He spoke softly, and his steel-blue eyes were always full of contagious enthusiasm for his work. Once convinced of a certain strategy, he was stubborn and insisted on his theories, but he could also adjust his models based on new experimental findings. His contributions inspired new generations of biologists to find beauty in algorithms and apply them to the study of life. As Hans was fond of saying: “So wird’s gemacht” – that’s how it’s done.

 

References

Akam, M. (1989). Drosophila development: making stripes inelegantly. Nature 341, 282-283.

French, V., Bryant, P. J. and Bryant, S. V. (1976). Pattern regulation in epimorphic fields. Science 193, 969-981.

Gierer, A. (1981). Generation of biological patterns and form: some physical, mathematical, and logical aspects. Prog. Biophys. Mol. Biol. 37, 1-47.

Gierer, A. and Meinhardt, H. (1972). A theory of biological pattern formation. Kybernetik 12, 30-39.

Gierer, A. and Schramm, G. (1956). Infectivity of ribonucleic acid from tobacco mosaic virus. Nature 177, 702-703.

Kirschfeld, K. and Reichardt, W. (1964). Die Verarbeitung stationärer optischer Nachrichten im Komplexauge von Limulus. Kybernetik 2, 43-61.

Maruyama, M. (1963). Second cybernetics – deviation-amplifying mutual causal processes. Am. Scientist 51, 164.

Meinhardt, H. (1980). Cooperation of compartments for the generation of positional information. Z. Naturforsch. 35c, 1086-1091.

Meinhardt, H. (1982). Models of Biological Pattern Formation. London: Academic Press.

Meinhardt, H. (1983a). A boundary model for pattern formation in vertebrate limbs. J. Embryol. Exp. Morphol. 76, 115-137.

Meinhardt, H. (1983b). Cell determination boundaries as organizing regions for secondary embryonic fields. Dev. Biol. 96, 375-385.

Meinhardt, H. (1984). Models for positional signalling, the threefold subdivision of segments and the pigmentation pattern of molluscs. J. Embryol. Exp. Morphol. 83 Suppl., 289-311.

Meinhardt, H. (1985). Mechanisms of pattern formation during development of higher organisms: a hierarchical solution of a complex problem. Ber. Bunsenges. Phys. Chem. 89, 691-699.

Meinhardt, H. (1986). Hierarchical inductions of cell states: a model for segmentation in Drosophila. J. Cell Sci. 1986 Suppl. 4, 357-381.

Meinhardt, H. (1995). The Algorithmic Beauty of Sea Shells. Berlin; Heidelberg; New York: Springer-Verlag.

Meinhardt, H. (1999). Orientation of chemotactic cells and growth cones: models and mechanisms. J. Cell Sci. 112, 2867-2874.

Meinhardt, H. (2002). The radial-symmetric hydra and the evolution of the bilateral body plan: an old body became a young brain. Bioessays 24, 185-191.

Meinhardt, H. (2006a). From observations to paradigms; the importance of theories and models. An interview with Hans Meinhardt by Richard Gordon and Lev Beloussov. Int. J. Dev. Biol. 50, 103-111.

Meinhardt, H. (2006b). Primary body axes of vertebrates: generation of a nearCartesian coordinate system and the role of Spemann-type organizer. Dev. Dyn. 235, 2907-2919.

Meinhardt, H. (2008). Hans Meinhardt. Curr. Biol. 18, R401-R402.

Meinhardt, H. (2015). Dorsoventral patterning by the Chordin-BMP pathway: a unified model from a pattern-formation perspective for Drosophila, vertebrates, sea urchins and Nematostella. Dev. Biol. 405, 137-148.

Meinhardt, H. and de Boer, P. A. J. (2001). Pattern formation in Escherichia coli: a model for the pole-to-pole oscillations of Min proteins and the localization of the division site. Proc. Natl. Acad. Sci. USA 98, 14202-14207.

Meinhardt, H. and Gierer, A. (1974). Applications of a theory of biological pattern formation based on lateral inhibition. J. Cell Sci. 15, 321-346.

Meinhardt, H. and Gierer, A. (2000). Pattern formation by local self-activation and lateral inhibition. Bioessays 22, 753-760.

Meinhardt, H. and Klingler, M. (1987). A model for pattern formation on the shells of molluscs. J. Theor. Biol. 126, 63-89.

Meinhardt, H., Koch, A. J. and Bernasconi, G. (1998). Models of Pattern Formation Applied to Plant Development. Singapore: World Scientific Publishing.

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Roth, S. (2011). Mathematics and biology: a Kantian view on the history of pattern formation theory. Dev. Genes Evol. 221, 255-279.

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Database Administrator and 2 Software Developer positions at Xenbase

Posted by , on 24 March 2016

Closing Date: 15 March 2021

Xenbase, the Xenopus model organism database (MOD), is building it’s developer team.

We a looking to hire 2 software developers and a database administrator. These positions are based at the University of Calgary, at the foot of the Rocky Mountains in Calgary, Alberta, Canada.

Ideally, we like to find people who have some biology background, or have worked in other MODs- (e.g., Zfin, Flybase, MGI) or biology databases (e.g., NCBI, UniProt, BeeGee)

Please share this job posting with anyone you think might be interested.

Two Developers: http://careers.ucalgary.ca/jobs/5247311-software-developer-biological-sciences-faculty-of-science

One DBA: http://careers.ucalgary.ca/jobs/5247363-research-associate-biological-sciences-faculty-of-science

Xenbase has received a new grant from the NICHD/NIH to fund its expansion over the next 5 years, but due to a rule about advertising jobs beyond the current grant year, the job ads say “7 months with possibility of renewal”. Don’t let this discourage anyone from applying!

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Lectureships in Biological Sciences, UEA, Norwich

Posted by , on 23 March 2016

Closing Date: 15 March 2021

New Lectureships are available in the School of Biological Sciences, University of East Anglia, Norwich. We are looking for dynamic individuals who complement and extend the activities in BIO in both research and teaching.

BIO’s research portfolio includes: Cell and Developmental Biology, Cell signalling, Musculoskeletal Biology, Cancer, Matrix Biology, RNA Biology and more information can be found on our Research pages.

Details and links to the application forms can be found on our current vacancies page:

ATR1302 (Lecturer in Bioinformatics)
https://www.uea.ac.uk/hr/vacancies/academic/-/asset_publisher/h0n2rDvu3ug8/content/lecturer-in-bioinformatics

ATR1303 (Lecturer in Biomedicine)
https://www.uea.ac.uk/hr/vacancies/academic/-/asset_publisher/h0n2rDvu3ug8/content/lecturer-in-biomedicine

ATR1304 (Lecturer in Evolutionary Biology, Ecology, conservation)
https://www.uea.ac.uk/hr/vacancies/academic/-/asset_publisher/h0n2rDvu3ug8/content/lecturer-in-evolutionary-biology-ecology-conservation

The closing dates for all the above posts are: 12 noon on 27 April 2016.

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Labome releases Validated Antibody Database (VAD) version 2.2

Posted by , on 22 March 2016

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Developmental biologists use antibodies extensively to study the gene expression during different stages.  However, there is a lack of specific antibodies against many proteins related to development.  In addition, some antibodies yield unspecific and/or irreproducible results.   To help alleviate this antibody quality and specificity problem, Labome sought to organize antibody applications cited in formal publication since 2008 and developed Validated Antibody Database  (VAD).  The most recent version, 2.2,  contains manually curated 143357 entries from 38430 formal articles, covering 35146 antibody products from 110 suppliers.   The suppliers include both commercial entities and non-profit organizations such as Developmental Studies Hybridoma Bank (DSHB) at University of Iowa, and Neuromab from University of California at Davis.   A small number of antibodies from academic researchers are included as well, if these antibodies are validated in knockout models.

One of the side benefits of our curation effort is the identification of cross-reactive species for many antibodies.  Antibodies tend to be developed for human/mouse proteins and tend to be tested by commercial suppliers for their applicability in human or mouse system.   Development models often use more readily manipulatable models such as flies, worms, zebrafish, and frogs.  Labome is able to obtain information about many antibodies having cross-reactivities with the model organisms from the literature.

The database is freely browsable at www.labome.com.    Information about antibody validation using knockout models is also posted at Labome Facebook page www.facebook.com/LabomeNews.

Feedback and suggestions are most welcome.  We hope to work with everybody to develop a useful tool.

 

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Postdoctoral Scientist (m/f)

Posted by , on 22 March 2016

Closing Date: 15 March 2021

Max-Planck-Institut für molekulare Biomedizin

 

The Max-Planck-Institute for Molecular Biomedicine in Muenster, Germany has an opening for a

Postdoctoral Scientist
(position-code 07-2016)

The position is available in the DFG Emmy Noether junior group of Dr. Ivan Bedzhov that is focused on understanding the self-organization of the pluripotent lineage in mammalian embryos at the time of implantation (I. Bedzhov and M. Zernicka-Goetz, Cell, 2014). The successful candidate will investigate the mechanisms of self-organization of the pluripotent epiblast in the context of the developing embryo and in vitro using embryonic stem cell as a model system.

We are looking for a talented and highly motivated post-doctoral scientist with strong cell and molecular biology background. Previous experience with RNA-seq analysis, genome editing and embryonic stem cells will be an advantage.

The Max Planck Institute for Molecular Biomedicine offers dynamic, multidisciplinary environment with state-of-the-art transgenic, imaging, genomics and proteomics equipment and core facilities. The working language in the institute is English. The institute is located in Muenster, a vibrant city with a highly international academic environment.

The position is initially available for two years with the possibility of extension. Starting date will be as soon as possible. All conditions for the employment will be according to the regulations of the contracts for the civil service (TVöD, Tarifvertrag für den öffentlichen Dienst) level 13 TVöD.

The Max-Planck society is committed to increasing the number of individuals with disabilities in its workforce and therefore encourages applications from such qualified individuals. Furthermore, the Max Planck Society seeks to increase the number of women in those areas where they are underrepresented and therefore explicitly encourages women to apply.

Please send your application (with the position-code 07-2016), letter of motivation, CV including a complete list of publications and the contact information of 2 referees to:
career@mpi-muenster.mpg.de
or
Max Planck Institute for Molecular Biomedicine
Roentgenstrasse 20
48149 Muenster
Germany

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