Each year, the British Society for Developmental Biology awards the Beddington Medal for the best PhD thesis in developmental biology. At the 2012 BSDB meeting, this award went to Boyan Bonev, who completed his PhD in Nancy Papalopulu’s lab at the University of Manchester. At the conference, Boyan gave a talk about his PhD work, describing how microRNA-9 promotes neural progenitor heterogeneity in a context-dependent manner. Find out more about Boyan’s work, and what he’s up to next, in this interview.

What was your thesis about?

My graduate work was about the role of the microRNA miR-9 in neural development. MicroRNAs are a really exciting part of the genome, because they’re small, non-coding RNAs. They were discovered about ten years ago, and since then there’s been a tremendous amount of research carried out to find out what exactly their role is. There are many occasions where microRNAs have an essential role, particularly during development. What I wanted to find out is how miR-9 regulates neural development, in particular in vertebrates. MiR-9 has a really interesting  expression pattern: the microRNA is present in the brain, but expressed differently in different parts of the brain. So, the really cool thing about miR-9 is that it turned out to have a context-dependent function, and this is really the key highlight of my thesis. It means that in some parts of the brain miR-9 does one thing, and in other parts it does something else. During development it also changes its function. For example, in my talk I talked about progenitor heterogeneity, and how miR-9 can regulate this, but we also looked at its function in mature neurons, where it does something else entirely, which is to modulate axon branching and axon extension. It’s really cool how nature seems to be using one molecular mechanism in a different way, depending on where you look along the anterior-posterior axis, or at which developmental stage the organism is, to get feedback about what decisions the cells need to make.

You showed work in both frog and mouse. Which one do you prefer to work with?

To be honest I find working with both of them really exciting. Working with frogs is a little bit easier, because they develop externally, so it’s easier to get sufficient numbers and it’s easier to manipulate them from the very beginning. They’re a really good model organism for studying early developmental events in particular. However, to work on something that is more closely related to the human brain, which is ideally what we want to understand, mouse is the better system. That’s why I started to work more and more on mouse, especially in the last part of my PhD. Other than that they’re both really nice organisms to work with.

In your talk you described how a microRNA target in turn regulates the microRNA. Is that a common mechanism?

There are not that many instances where such negative feedback regulation is known, but I think it’s becoming more and more prevalent that this is indeed a very interesting type of regulation. Not just for microRNAs, but also in the case of transcription factors with negative feedback loops. I think what is really important to consider is that these transcription factors and microRNAs do not work in isolation – they all work together with all their partners. And these kind of feedback loops, whether they are coherent or incoherent feedback loops, are the ones that buffer against developmental noise or reinforce a decision. In our case this was a negative feedback loop that was doing both, because it was promoting oscillations, but it was also reinforcing developmental decisions.

What are you doing now?

I was supposed to have a bit of a long break between my PhD and before I started my postdoc, but it boiled down to about ten days in the end. Right now I’m going back to my home country, Bulgaria, to have the rest of the ten days off. At the end of the month I’m leaving for the States to start working on my postdoc.

What will you be doing in your postdoc?

That’s going to be another cool and exciting project. It’s also related to non-coding RNAs and neural development, but it’s completely different from what I’ve been doing so far. It focuses on a different, newer, type of non-coding RNAs: long non-coding RNAs. I told you that microRNAs are about ten years old – well, these long ncRNAs are about 3-4 years old.

I’m going to Harvard, where  I will be working in the lab of John Rinn, who is one of the guys who discovered long ncRNAs, and in Paula Arlotta’s lab, who is an expert in mouse neural development, in particular mouse cortical development. I’m going to be working with both of them to try to figure out the function of long ncRNAs in mouse neural development.

Do you have any advice for new PhD students?

Be persistent. At some point, things will probably stop working, and you’re going to be struggling to figure out why they’re not working. What I always say is that the result is the result. Your inability to figure out why it is like that is the problem. But usually things like technical difficulties or problems with the model organism have a meaning, and you have to be persistent and really go down to the details to figure out what’s going on.

Bonev, B., Pisco, A., & Papalopulu, N. (2011). MicroRNA-9 Reveals Regional Diversity of Neural Progenitors along the Anterior-Posterior Axis Developmental Cell, 20 (1), 19-32 DOI: 10.1016/j.devcel.2010.11.018

Dajas-Bailador, F., Bonev, B., Garcez, P., Stanley, P., Guillemot, F., & Papalopulu, N. (2012). microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons Nature Neuroscience, 15 (5), 697-699 DOI: 10.1038/nn.3082

(5 votes)

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Abstract deadline: 27 July 2012 | Registration deadline: 1 September 2012

Building on the success of last year’s event, ECD 2012 will bring together scientists from the fields of epigenomics, genetics and bioinformatics to discuss the latest developments in this fast-moving field. This Wellcome Trust conference will discuss recent advances focusing on genome-wide approaches that are revolutionizing the field. Recent technological developments have made it possible to conduct epigenome-wide association studies (EWAS) to investigate the link between changes to the epigenome and the development of disease. Sessions will include: epigenomic studies across of a range of common diseases, including psychiatric and neurodevelopmental disorders and diseases of the immune system; model organisms and model systems; mathematical approaches to epigenomics; intergenerational and environmental effects; and translational epigenomics.

Abstract submission is strongly encouraged as a significant number of presentations will be selected from the abstracts.

Scientific organising committee:
Stephan Beck, University College London, UK
Susan Clark, The Garvan Institute of Medical Research, Australia
Andy Feinberg, Johns Hopkins University School of Medicine, USA
Anne Ferguson-Smith, University of Cambridge, UK

Venue:
Johns Hopkins University
Baltimore, MD, USA

Keynote Speakers:
Shelley Berger, University of Pennsylvania, USA
Bert Vogelstein, Johns Hopkins Kimmel Cancer Center, USA

Invited Speakers include:
Stephan Beck, University College London, UK
Jessica Connelly, University of Virginia, USA
Daniele Fallin, Johns Hopkins Bloomberg School of Public Health, USA
Andy Feinberg, Johns Hopkins University School of Medicine, USA
Doug Higgs, University of Oxford, UK
Tim Huang, University of Texas Health Science Center, USA
Barbara Knowles, ASTAR, Singapore
X. Shirley Liu, Dana-Farber/Harvard School of Public Health, USA
Shalini Oberdoerffer, National Cancer Institute, USA
Dirk Schübeler, Friedrich Miescher Institute for Biomedical Research, Switzerland
Amos Tanay, Weizmann Institute, Israel
Toshikazu Ushijima, National Cancer Center Research Institute, Japan

For more information: https://registration.hinxton.wellcome.ac.uk/display_info.asp?id=298

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The sophistication of genetic tools and the relative ease of breeding and housing mean that the mouse is the most widely used mammalian organism for basic and biomedical research. The genotype-phenotype information that will emerge from the efforts of the International Mouse Phenotyping Consortium (IMPC), now well into its first year, will advance all areas of the biological sciences, from behaviour to drug discovery, oncology to developmental biology.

The IMPC is one of the largest model-organism-based initiatives ever funded. Its aim is to generate and comprehensively characterise the phenotypes of viable knockouts for every gene in the mouse genome, and to compile the information in a public database (Brown & Moore, 2012). In practical terms, this means creating ~20,000 viable mouse lines and phenotyping them using dozens of tests, a feat that will be carried out through the coordinated efforts of several institutes in nine different countries. Moreover, the ~30% of knockouts that are expected to show embryonic lethality will be characterised, where possible, using specialised tests performed during embryonic development. The number and sophistication of tests used for phenotyping will likely increase as the protocols are refined and improved, and as notable mouse strains are selected for specialised phenotyping in secondary screens. For example, histopathology – the analysis of disease correlates through microscopic examination of tissues obtained from necropsy or biopsy – provides invaluable information that is complementary to in vivo assays, but it can currently only be performed on selected lines owing to economical and logistical constraints (Schofield et al., 2012).

The resources that will be generated by the IMPC include free access to all knockout mouse lines (or sperm) and a comprehensive database of corresponding phenotype information. These resources generated will be of value to investigators at all levels, and in many disciplines, from undergraduates to group leaders, basic scientists to clinicians.

Further reading

Brown, S. D. M. and Moore, M. Towards an encyclopaedia of mammalian gene function: the International Mouse Phenotyping Consortium. (2012). Dis. Model. Mech. 5, 289-292.

Schofield P. N., Vogel, P., Gkoutos G. V., Sundberg, J. P. (2012). Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice. Dis. Model. Mech. 5, 19-25.

Straight talk with… Steve Brown. Interview by Hannah Waters. (2011). Nat. Med. 17, 1332.

January 2012 DMM Podcast: Paul Schofield on histopathology in high-throughput phenotyping of mutant mice.

IMPC website: http://www.mousephenotype.org/

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Now the real adventures begin. We arrived at the field station on Sunday and met with The Fixer on Monday afternoon to discuss arranging a driver for the next week or so. We explained to him what the goals are, where we’d like to go, the time of day/night, duration of the trip, and asked for a price estimate before we go to negotiate with the drivers. There are a bunch of drivers at the market, so I figured we’d just go that way and see who gives us the best price. He started to go on about how it’s complicated to say how much it will cost because of variables like the time, road conditions, etc. I just wanted a ballpark for price per kilometer or price per hour so I’d know what to expect and where to start. Somewhere in these negotiations, a driver pulled up – a friend of The Fixer who he wanted us to hire. At some point in the “it’s complicated” negotiations that a Chinese student (Yang) was trying to help me with, Sarah interrupted and took over negotiating for me. The whole game changed. She got them to understand that it doesn’t have to be complicated because they already know all of the variables. She also got them to agree to an estimate for the first day with room for each side to negotiate if either I or the driver don’t think the price is fair. The Chinese student seemed a little astonished that this worked so well, and it validated the argument I’d been making about her value to the institute – she managed to help reach an agreement far more quickly than if we’d done things in a more Chinese and left room for flexibility on both sides. This was probably only possible though because I’ve cultivated a reputation for honesty.

So off we went to explore the desert. We visited the location I’d gone to a few weeks ago along the oil highway where I’d seen lots of tracks and where we’d been told there are lots of 3-toed jerboas. One of the things Talia wants to do is to take soil compaction measurements using a penetrometer. It’s not as dirty as it sounds. It’s basically a hand held tool that measures the amount of force it takes to press a small foot into the ground by a set amount. She’s been taking readings in all of the different locations and at the top and bottom of sand dunes and samples of the earth so that she can better understand the environment with which the jerboa feet are interacting as they bound along.

We had planned to visit another location last night, but we got distracted instead by camels. It’s just one of those times when you sacrifice a little bit of work for an amazing experience. A Kazakh family with a house by the roadside had about a half dozen baby goats that had lost their moms, so that was pretty cute to begin with. But then we rounded the corner of the house and walked over to where there were three mamma camels with their babies. Soooooooo painfully cute. They even have little baby humps. But a baby camel is no small fry. Each of these little guys was probably no more than a couple weeks old but already stood at about my shoulder. The mamma camels were a bit unpredictable, and I kept expecting to get clocked by a giant head suspended on a long neck. At one point, one of the gals started to walk toward me, but they each have a rope tied to one foot, so she accidentally stepped on the rope and managed to hobble herself. Good for me, because I think she had more than “hello” in mind.

This morning we went to make up for the lost hours last night and visited a couple of other jerboa capture sites. More camels! We had to wait for a whole herd at a camel crossing before we could continue on the road to a flat dry field where the 5-toed jerboas are supposedly prevalent. So once we had the lay of the land, we returned to the field station where everyone else took an afternoon siesta, and I got a little work done before we set out to lay some traps in a field near here. We will probably only catch sand rats (gerbils/jirds), but since Talia wants to compare bipedal and quadrupedal rodents, those are still useful.

After dinner this evening, we set out once more to a place where we were told there are both 5 and 3-toed jerboas. I walked along the top of the dune with my headlamp sweeping slowly in each direction and managed to see about a dozen 3-toed jerboas. Mostly though I just got good at spotting spiders since their eyes also glow in the light, but they’re much smaller than rodent eyes and kind of green in color. The jerboas are really quick though, so about all I got to appreciate was their escape maneuvering as their eyes bounced off into the distance. Fortunately my companions are a little quicker and managed to net a jerboa and a sand rat before we left that area. The driver was super helpful also. He stayed with the car, but every once in awhile he would flick on the headlights and change position so he could highlight animals for us. I think he finds this whole adventure to be funny and fun at the same time.

On our way out of the desert, along a dirt road, we saw a whole bunch more 3-toed jerboas, and Yang eagerly hopped out to chase them down. I think he wore himself out, but he was successful and caught another two jerboas before we left the desert. We then stopped at a place where there were supposed to be 5-toed jerboas but didn’t see any until we were leaving along a paved road and caught sight of them in the headlights of the car hopping down the road. The driver passed the first one by before realizing we wanted to stop and try to catch it, so he threw the car into reverse. I remember saying “it’ll be either gone or squished” not really expecting the latter until we once again passed it and saw the poor thing lying in the road. The good thing is that he didn’t feel anything for long, but I can’t understand why he didn’t hop out of the way. Fortunately we caught two more alive also along the road, so Talia now has some research subjects for her filming.

(1 votes)

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Registration deadlines:

April 29 – Early registration and abstract submission deadline for the third meeting of the European Society for Evolutionary Developmental Biology (EED)

April 30 – Registration deadline for Molecular & Cellular Basis of Regeneration & Tissue Repair (EMBO conference and BSDB Autumn Symposium)

May 28 – Early registration deadline for the SDB meeting
June 4 – late abstract submission deadline for the SDB meeting

[added 26/4] June 1 – Abstract submission deadline for the Santa Cruz Developmental Biology meeting.

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Unless it’s a Przewalski’s horse!

Oh where to even start! The embryo collections came to completion on Wednesday, and now we are on to Phase II. We returned to Urumqi on Thursday so I could give a talk at Xinjiang Normal University and we could pick up Talia at the airport on Friday. Sarah and I decided to take the public bus back to the city since we weren’t carrying much and were feeling adventurous. That involves taking a local bus for about 50 cents from 222 to Fukang and then the long distance bus from Fukang to Urumqi for about $2. By the way, in past years I thought the town near the field station and the city 20 minutes away were both Fukang. I always called one Fukang town and the other Fukang city. But this year I finally learned that the agricultural community here near the field station is “Regiment 222”. There is a long back history that I will leave you to explore and question for yourself.

Upon returning to Urumqi, Sarah and I met up with our friend from one of the labs here who is delightful. She spent a couple of years in Reno as a postdoc, so she’s familiar with American culture and personalities. Sarah wanted to introduce me to Pizza Hut in China, which is a fancy date destination. We did a sampling of the menu and stayed until close – cackling so much we probably interfered with a few romantic evenings. It started because I had been waiting on the bus while Sarah went to the market in 222 to get water and yogurt for the trip. To entertain myself, I was looking up the word for “wrench” that I had learned from a student at the field station when I wanted to take the regulator off our CO2 tank. Chinese is made up of a lot of compound words, so the word for wrench is ban (to pull) shou (manually). I have a dictionary on my phone that gives the meaning for each character and other compound words that use that character, so I accidentally discovered another compound word using the character shou that has a sexual meaning. I had shared this discovery with Sarah who not so innocently brought it up to our friend in the way of “I learned a new word”, and she intentionally pronounced it with the incorrect tone so that our friend would puzzle it together to figure out what she was asking. Her face exploded in shock, and she laughed. So that started a whole conversation about the worst words in English and Chinese, and I realized that learning a bad word as an adult doesn’t give it the same meaning. She could throw around some of the worst words in English as though she was saying “table” and “chair”, but when we asked her to tell us bad words in Chinese it was like we were asking her to stab her own hand. Likewise, we could toss around those words playfully in Chinese, but there is no visceral meaning. It’s as if you have to have had your mother threatening to wash your mouth out with soap to really feel the wrongness of a word.

On Friday morning, I was picked up and delivered to Xinjiang Normal University to give a talk in the biological sciences department on invitation from my hosts at the arrival banquet. They are all really friendly and enthusiastic to have me here. After my talk and tour of the natural history museum (great teaching resources), we walked across from the campus to a restaurant for another lunch time banquet. This was more informal than the baijiu fest from the first night, but again the fish hit the table and bottles of pijiu (beer) were opened. Speeches all around. The dean of the college of life sciences couldn’t make it to my talk but made an effort to come for lunch even though she was only able to join for the last half. She said she likes me. I joked that it’s because she knows I can drink well. She’s great. We talked a little about careers as women, and I asked about the numbers of women who start careers in biology at the masters level compared to the number of women who achieve full professorship. The Normal universities are teacher’s schools, so there is a slightly higher percentage at her institution, but it still hovers around 20% even though greater than 50% start out at the lower levels. I knew what the answer would be but asked “Why?” anyway. Of course she said, “Because they want to devote their time to family.” I asked if she thought it would ever be possible in China for men and women to both contribute equally to caring for the family so that both could have fulfilling careers if they want, and she said “No” (even though she later said that she is married and has a son, and her husband is very supportive which is what allowed her to reach the position of dean). One of the young men on the faculty who is recently married loudly protested and started arguing with her that yes, men will take on a more equal role and support their wives. I didn’t understand the rest of the argument since it was all in Chinese, but a young woman across the table from me who is a new professor and has a 15 month old son of her own just stared at me with amazement at what I’d started. I just gave a little grin and a wink to let her know I knew exactly what had happened and watched the debate unfold.

Later that evening, Talia arrived from Boston, and I managed to successfully retrieve her from the airport even though I hadn’t written down any of her flight info, didn’t know her airline, and didn’t know what terminal she was flying into. Thank goodness for small airports. I’m terrible about doing things like this. We kept her up the first night and planned outings for Saturday to get her over the jetlag. Sarah knew of a vegan restaurant she wanted us to try since Talia is vegetarian, and Xinjiang is the Chinese equivalent of Texas. We had several of the common Chinese dishes, except that everything that looked and tasted a lot like meat had no animal components at all. Really interesting. We then met up with my Uygur friend to go south to where I’ve lived before, because I wanted to show Talia all my favorite places and let her and Sarah get to know my dear friend. We got out of the cab, and it was an immediate sensory overload. The food vendors were starting to set up their carts in the area of the night market, so we wound our way through the rows of tumeric dusted roast chickens, sheep’s heads, and mounds of glass noodles. Talia and Sarah decided to get some sort of frighteningly fake sweet beverage because it was a shooting fountain of neon orange. We darted into a Uygur medicine shop where a man read our health histories in our pulses. I think he was a bit of a quack though – I’ve done this before and felt like the guy who saw me was at least paying attention to my skin tone and the health of my fingernails. This guy seemed a little cocky, barely looked at me, and his major comment was that I don’t absorb enough nutrition from my food. Not a startling discovery.

The narrow side streets are bustling with foot traffic, so we inserted ourselves in the river and wandered about watching as all the locals did their evening shopping. The tourist markets were all closing, but they mostly sell a bunch of kitschy things that aren’t made in this area anyway. It’s far more fun to roam the streets with the guys selling t-shirts and shoes shouting “Besh quai, besh quai, besh quai!!!” which means 5 RMB in Uygur. I made one guy laugh by joining in his call and smiling to let him know I wasn’t making fun of him. We found ourselves passing a halal butcher right after they had decapitated a lamb. It hadn’t yet been eviscerated, but the pelt lay in a pile on the ground, the head and feet were no more, and it was hanging by a wire cable threaded through the Achilles’ tendons over a bucket of fresh blood. Had we only passed by 10 minutes earlier, we would have gained a new appreciation for where our food comes from.

Wandering these streets again with my friend brought back a flood of memories from past years, as he and I reminisced shops we’d been to, funny things we’d seen, dinners we’d had. It was nice to share memories and tell Sarah and Talia our stories while watching them write stories of their own. And I keep learning more and more about Islam and life in this part of the world that hurts my heart and brain to think about how little we as Americans really know about this great big world past our borders. After yet another fantastic meal and amazing conversation, the three of us girls left my friend behind since that neighborhood is his home and hopped back into a taxi to return north to the institute. Once we got to the hotel, I kept Talia up another hour sharing my experiences and observations of the ethnic culture clashes of this region, and right as we were drifting off to sleep at a quarter to 2 am, I got a text message to my Chinese cell phone. It was a professor at the institute who wanted to be the one to bring us back to the field station asking what time he should meet us. Seriously. He sent me a message at 2 am. Sarah had warned me about this. The phone culture is strange. They can call or text at any time from anywhere, and it’s all okay. So I replied politely, said I was going to sleep, and turned off my phone.

This morning after some lengthy discussions and slight political issues, we arranged for him to pick us up since he really wanted to take us to the Przewalski’s horse breeding center. That was worth the 2 am text message and ensuing drama. And worth braving the dust storm. Somehow overnight the temperature dropped about 40 degrees, and the winds came howling in from Russia. If I wasn’t Russian before, I am now on the inside and out. I feel like my eyeballs, my skin, and the insides of my nose and ears are coated with the dust carried from the winds of the north. But it was worth almost being lifted off my feet to see these amazing horses. Apparently before the breeding center started in 1985, there were only about 2,000 Przewalski’s horses in the wild. They are a species of wild horse that is native to Xinjiang, Inner Mongolia, and Mongolia (Inner Mongolia is a province of China. Mongolia is a country.) The breeding center started with 18 horses and now has a population of about 400. They have been reintroducing many of the captive bred horses into the wild, and have managed to have a real positive impact on the population of this species. They are truly wild horses. They are smaller than what you think of as a horse and look more like a donkey or a mule with a short mane and short flat tail. They still have most of their thick winter coat, and the younger horses look like they are wearing leg warmers. And they are mean! They get really grumpy and fight with each other. They have to be kept in families of one male and about 5-6 breeding females. Even the females will fight with each other. When one gets irritable, she backs her rump into another and just keeps pushing and pushing until the other gets annoyed. Then they separate just enough to get a good kick it. But it isn’t just a kick. It’s an ears back, teeth bared, two-footed bucking kick. Sarah kept making noise to spook and separate them, but that’s just what they do. They’re really truly wild horses.

The rest of the drive was fascinating. All along the mountains is mining country, so there are great big holes in the earth surrounded by digging equipment. And even though it isn’t a major oil field like what we wandered into up north, there are pumpjacks dotting the landscape. In addition to that, it’s a major industrial zone, so one after another we passed by some sort of manufacturing/mining/power station/etc type of location. The air was thickly brown with the dust, but not just from the dust. All around are mounds of coal piled high, and the dust from the coal gets picked up in the wind right along with the barren earth and sand. So it’s no wonder when I scratch my face, the underside of my nails is black. In fact, I have been writing this while waiting for my hot water heater to warm up. I think that ought to be done by now, so I’m going to shower my nasty self and get to bed.

(4 votes)

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Two weeks ago the Guardian newspaper, the safe port of call for most left-leaning liberal academics in the UK, devoted its entire front page to the rise of open access publishing in what it called ‘The Academic Spring’. For those of us working at the coalface, whilst this exposure was and is entirely welcome, it feels a little premature. Can we really compare the open access movement to the Arab Spring? And what would constitute an ‘academic’ Spring anyway? Much of the article’s emphasis was on the move by the Welcome Trust to jump on the  ‘academic spring’ bandwagon ostensibly begun by the Field Medal-winning Tim Gowers, the Rouse Ball Professor of Mathematics at Cambridge.

Gowers delivered a blog post on 21^st January protesting at the exorbitant practices of the Dutch publisher Elsevier, not least of which is the exceedingly high subscription rates they charge universities. In essence, the argument runs that the situation, whereby public money funds scientific research by academics that is submitted to learned journals for free, peer-reviewed by academics for those same journals for free, and then that same research is sold back to academics in the form of huge subscription charges paid ultimately by public money, is not just unsustainable but immoral. It is an argument that has received much support both within and outside the scientific community and has been at least partially responsible for Wellcome’s announcement that all research funded by them must be freely available six months after publication. The thinking goes that this will encourage academics to publish their work in open access journals and platforms, and it just so happens that Wellcome’s own new open access journal eLife, is about to start accepting submissions.

Please don’t misunderstand me; there is much to be said for open access publishing and for large funding bodies throwing their weight behind it. Likewise, the movement to reform the business models of huge publishing companies such as Elsevier that Prof. Gowers has spawned (almost 10 000 academics have signed up to www.thecostofknowledge.com, the advocacy site taking on Elsevier) is without question in the long-term interests of science and the academic enterprise.

The Arab Spring though, was (and hopefully is) a movement that has ousted (and hopefully will oust) repressive military dictatorships across the Middle East. To couch the debate over publication business models in the scientific world in the language of this outpouring of popular will seems to me a bit misplaced. Such as it is, the academic spring is not a movement directed at individual governments, but at international business practices – in that sense it shares more in common with the Occupy movement than the Arab Spring. It is not an undirected and unpredictable public protest movement, but a quiet and deliberate articulation of objection to a single company, in adherence to a well thought through and principled position. It is then, certainly academic. I’m just not sure it has sprung yet.

All the emphasis on the type of publishing market that would best serve science has in my view distracted from the fact that there is a much more fundamental issue that undermines the scientific enterprise in the 21^st century: the existence (or rather the perception of the existence) of a market in ideas. The idea that the fruits of research are quantifiable pervades current thinking. They are not. In a sense this perception parallels (at least in the UK) the move by successive governments to treat education more generally as a market, where consumers (families) ought to have choice between products (schools and universities). In terms of science, governments, funding bodies and universities, in that order, are responsible for this. The notion that it is possible to define in a short period of time the ‘outcome’ of scientific research is one that has pervaded recent thinking in the distribution of scientific money in particular in the UK but also, I think, everywhere else. Indeed, the idea that measuring such outcomes or their impact (I hate that word!) is an excellent way to judge the quality of an educational institution is almost unquestioningly accepted, it seems, by those in power. I would argue that measuring the outcome of research is not only inappropriate: it is impossible.

And this is where we come back to the business model of scientific publication. Basing the funding of the scientific enterprise, and the people that accomplish it, on publication outcomes is as short-sighted as it is prevalent. The rise of open access publishing may help, but the real problem is that there is no alterative to judging people by the cachet of their publications. In a world where the amount of scientific literature continues to spiral upwards, and where financial pressures mount on governments, in terms of both allocating their science budgets, and assessing how to do so, the appeal of using statistics and metrics to short-cut good judgement is perhaps inevitable. Likewise, the insistence of funding bodies on concrete direct consequences of the research they fund that are demonstrable to their political paymasters are understandable. Finally, the duty of universities to play the game and jump through whatever hoops are necessary in order to maximise their income from both government and competitive research grants is self-evident. The problem with all of these things is that they, and the system they constitute, rest upon a fundamental philosophical flaw: that it is possible to rank scientific research. There is no such thing as a market of ideas unless you give them a monetary value and sell them to somebody. But there is no alternative that has been articulated by anyone, even despite the growing recognition of the inherent problems in the scientific structure. The real academic spring has not yet sprung.

(7 votes)

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Here are the highlights from the current issue of Development:

A TOR de force in the haematopoietic niche

During development and homeostasis, it is essential to coordinate growth with the availability of nutrients. The interconnected insulin/IGF (IIS) and target of rapamycin (TOR) pathways integrate tissue growth with dietary conditions in Drosophila, and now Marc Haenlin and co-workers show that these pathways play a crucial role during haematopoiesis in the Drosophila lymph gland (p. 1713). The larval lymph gland contains a group of stem-like progenitor blood cells (prohaemocytes) that are kept in an undifferentiated state by cells of the posterior signalling centre (PSC), which serves as the stem cell niche. The researchers show that the IIS and TOR pathways regulate the size of the haematopoietic niche by regulating cell size and cell proliferation in the PSC. In addition, they show that IIS and TOR signalling are required in prohaemocytes to control their maintenance, and disruption of these pathways, induced genetically or by starvation, results in the precocious differentiation of these progenitors. Importantly, these studies highlight that blood cell development is coupled with nutritional status.

A MAP(K) of germline self-renewal

Spermatogonial stem cells (SSCs) have the remarkable ability to self-renew and support spermatogenesis throughout life. It is known that fibroblast growth factor 2 (FGF2) promotes SSC self-renewal but the factors acting downstream of FGF2 are unknown. Here, Takashi Shinohara and colleagues show that FGF2 regulates SSC self-renewal via MAP2K1 and the Etv5 and Bcl6b genes (p. 1734). Using an in vitro mouse germline stem (GS) cell culture system, the authors show that GS cells require FGF2 for continuous proliferation, and that a specific MAP2K1 inhibitor reduces GS cell proliferation and MAP2K1 phosphorylation. By analysing target genes that are regulated by MAP2K1, the researchers identify Etv5 and Bcl6b, and show that overexpression of these genes in GS cells promotes proliferation in an FGF2-independent manner, confirming that they act downstream of MAP2K1. Furthermore, transplantation of Bcl6b-expressing GS cells into mouse testes induces germ cell tumour formation, suggesting that excessive self-renewal can promote tumourigenesis. The identification of these genes provides key insights into the mechanisms controlling SSC self-renewal.

Notch tips the balance in the pancreas

In the developing pancreas, the branched epithelium can be separated into tip and trunk regions, with the tip domain generating acinar cells, and the trunk domain differentiating to endocrine and duct fates. Although Notch signalling is known to be important for proper pancreatic development, particularly in maintaining the progenitor state and inhibiting premature endocrine differentiation, its precise roles in regulating cell fate remain unclear. Here (p. 1744), Jan Jensen and co-workers disrupt Notch signalling in the mouse in a mosaic fashion, revealing a function for Notch in regulating trunk versus tip cell fate. Overexpression of a dominant-negative Mastermind protein, which blocks Notch-dependent transcription, leads to loss of endocrine and duct cells, suggesting that Notch signalling promotes trunk cell identity. Mechanistically, Notch promotes the expression of the trunk-specific transcription factor Nkx6.1, via direct binding of RBP-jκ at the Nkx6.1 promoter. These data thus establish a crucial role for the Notch pathway in directing endocrine and duct cell differentiation in the pancreas.

Eve and Grain guide the way for axon pathfinding

Accurate axonal pathfinding relies on the tightly regulated expression of guidance cues and their receptors, but the links between transcriptional regulators and downstream guidance factors are poorly understood. Genetically amenable Drosophila motoneurons provide an ideal system for analysing the control of guidance receptor expression. It is known that two transcription factors, Even-skipped (Eve) and Grain (Grn) are expressed in the aCC and RP2 motoneurons, and that projection of these neurons to the muscle requires the Netrin receptor Unc-5. Now, Juan-Pablo Labrador and colleagues dissect out the relationships between these factors (p. 1798). The researchers find that Eve and Grn independently promote Unc-5 transcription, and that both are required to generate sufficient Unc-5 expression for proper pathfinding – likely via an enhancer element in unc-5 intron 5. Overexpression of both Eve and Grn in another motoneuron population induces ectopic Unc-5 and hence axonal redirection. Thus, the combinatorial effects of these two transcription factors together direct expression of the key guidance receptor, and so define the axon’s path.

Planar cell polarity: fattened up

The atypical cadherin Fat (Ft) is crucial for planar cell polarity (PCP) in Drosophila. Four ft homologs (Fat1 to Fat4) have been identified in mammals, but the functional roles of these homologs and any possible redundancies between them are unclear. Here, Helen McNeill and colleagues study the genetic interactions between mammalian Fat genes and show that Fat proteins act both synergistically and antagonistically to regulate multiple aspects of tissue morphogenesis in mice (p. 1806). For example, the authors show that Fat1 and Fat4 synergise during kidney, cochlea and cranial neural tube morphogenesis. Importantly, the researchers also show that the effects of Fat4 are modulated by atrophins, which are known components of PCP signalling in Drosophila, suggesting that Fat-atrophin interactions play an essential and conserved role in planar polarity. These findings reveal a high degree of complexity in mammalian PCP and highlight the wide-ranging effects of Fat cadherins on animal development.

Complexity in the kidney

The kidney comprises multiple cell types of both epithelial and mesenchymal origin, with highly defined regional subdivisions in the ductal systems. A full understanding of kidney development requires that each cell type can be uniquely identified by specific molecular markers. To this end, Andrew McMahon and colleagues have undertaken a comprehensive analysis of the RNA expression patterns of nearly one-thousand transcription factors in the embryonic mouse kidney (p. 1863). Their results not only identify novel markers, but also reveal an unexpected degree of restriction in expression of many factors, suggesting that anatomically defined compartments may be further subdivided at the molecular level. Moreover, this in situ dataset provides a starting point to understand the transcriptional networks underlying cell type specification. As proof of principle, the authors use published microarray and expression data to bioinformatically identify putative targets of five transcription factors and to uncover potential network topologies. This valuable resource has been made available to the community via the GUDMAP database.

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Have you ever thought about the future of developmental biology? Over the past decades, developmental biology has changed a lot. We have different tools, do different types of experiments, collaborate with different disciplines, and even fund and publish research in different ways. But which changes are still to come? What will the future bring?

If you’d like to share your thoughts about the future of the field, the Node and Development invite you to participate in our essay competition “Developments in development”. Your essay can describe the direction of a particular area of research, the emergence of new techniques or model organisms, career prospects, ethics, publishing, policies or other topics that will shape the future of developmental biology research.

A panel of judges will select the top entries, after which a public vote on the Node will determine the final winner. The winning essay will appear in Development later this year. All finalists posted on the Node will receive an Amazon gift certificate worth £50.

Judges:
Olivier Pourquié – Editor-in-Chief of Development
Claire Ainsworth – science writer

This competition is open to anyone who is involved in developmental biology research, or related fields (such as stem cell science or genetics), or has been within the past three years. PhD students, postdocs, and lab heads all qualify!

Please note that the final essays as selected by the judges will not be copy-edited before they appear on the Node. If you’re not confident about your English grammar and spelling, we recommend that you have a (near-)native speaker read over your essay before submitting it. The final winning entry will be copy-edited before publication in Development.

Deadline for submission is July 2nd, 2012 (noon GMT).
Maximum length: 2000 words
Please submit your essay, with a title and your name, as a Word attachment to thenode@biologists.com, and include a brief biography in your email (not in the essay).

More information can be found in the full competition rules, and in our terms and conditions for competitions.

We’re looking forward to reading your entries, and hope that you have fun writing!

(7 votes)

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Let’s start off this list with Pee. In. My. Face.

The Chinese collector folks brought a big cage with a *ridiculous* number of 5-toed jerboas this morning. They are apparently far more plentiful and easier to catch. Unfortunately, they were more plentiful last night than in the area they went the night before when they brought me 3/5 that were pregnant with nice stages, but this time I wound up with only 6/55 with anything useful. Most were either just about to give birth or already had. So I think what makes the biggest difference is the local population size (the probability of them having met a mate early in the season). When they change to a new location to make more money, it affects my harvest rate. Bummer. But further validation of my base rate plus “perfect embryo bonus” pay structure, so I can now convince them to go back to the other place even though it’s a little more difficult.

Anyway, back to the hazards. There were a lot of males in this batch, because it is much harder to distinguish male from female in this species. Since I am only paying for the females, I had to check and sort each one. By much harder, I mean that in both species the junk is all internal. With the 3-toed jerboas, you can tell without too much difficulty by the anogenital distance (further apart in males than in females). That’s much smaller in the males of this species. So with these guys the best way to tell is to press down on either side to make the business bits pop out. I’ve done this also with the 3-toed guys and met with no great peril other than an attempted bite of my well-protected hands. So I was inspecting one of the animals who turned out to be male, out popped his penis…and a very thin but highly pressurized fountain of urine sprayed across my chin and thankfully (barely) missed my mouth. This happened a couple of times (second time across my shoulder since I quickly learned to aim away from my face). There was also the one that launched herself out of my hand and scurried under the fume hood. The guy who had delivered the animals though this was all the most hilarious show.

Up to this point I had thought it was bad enough that I have to swat away mosquitoes while dissecting if we’re working into the evening. And all along I’ve had to maintain my ninja-like skills of crushing the errant flea who tries to make an escape for a warmer body. Add to that the mental health burden of feeling like an executioner each day going through more and more animals. I keep telling myself that this will set up the next 2-3 years of my career, and if I were to spread this out over that amount of time, it would be no different from the number of mouse dissections I do. But it’s much more challenging when it’s compressed into two weeks of intense work.

(2 votes)

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