I am a graduate student from Indian Institute for Science Education and Research (IISER), Pune, India. I wish to share some of my work and life experiences in Japan from a recent visit. Our lab works on development and evolution of insect wings. I am interested in understanding the development of lepidopteran wings using Bombyx mori ( silkmoth) as a model system. Initially at my place it was an ordeal working experiments mostly for the lack of technical expertise on silkmoth experiments and lack of availability of resources.

We decided to carry out some experiments in the University of Tokyo, Kashiwa campus to study the development and evolution of insect wings, specifically lepidopteran wing development, using the silkmoth as a model organism. Expertise on studies in silkworm development is abundant in Japan as there are many research groups working on this various aspects of silkworm development. To be housed in one of the best universities in asia was a privilege and the facilities and research truly matched the stature of one of the best institutes in the world.

I was in Prof. Haruhiko Fujiwara’s lab which works on Silkworms, Butterflies and different aspects of their genetics and development. The facilities in the lab were really state of the art, organization of the lab was immaculate and expertise vast which helped my work progress smoothly. One hurdle was definitely that of the language which I should admit was a more than what I anticipated, most people in the campus speak in Japanese, study and even discuss science in Japanese, but it seemed trivial with the kind nature of the people, every time they put an effort beyond their way to help you in every situation in lab or on outside. A little Japanese learned beforehand came in handy at times and also got a smile across people there who always appreciated generously for every one of my efforts to speak their language.

I started experiments here as soon as I came in but for a week or so they really did not work as I had to get adjusted to the setup and find the reagents and understand the instruments (some of which had complete Japanese menus!). With the help of the friendly lab members things moved rapidly and was able to understand the techniques they used and apply to solve issues which had troubled me in research so far. In a lab of around 20 people everyone chipped in whenever I had problems to trouble shoot with the best they could and made work progress fast and life easier. The discussions with my sensei (used to address professor in Japanese) were very helpful to understand the development of silkworm and to apply techniques like immuno histochemistry and RNA in situs. As these experiments were done in the lab on a regular basis and also the worms were studied extensively here, hence work moved smoothly and results were easy to come once I was settled in. I could work out all the standardization of Chromatin Immunoprecipitaion (ChIP) with the abundant silkworm resource which was excellently maintained. There wasn’t a single hindrance for an experiment no matter when I wanted to perform them because of the excellent maintenance of the larvae and the whole-hearted support of the lab.

During this trip I also had a golden opportunity to interact with other developmental biologists at the JSDB 2010 meeting at Kyoto. The discussions in the conference included various interesting aspects of developmental biology ranging from growth control, organogenesis to mathematical modeling. The meeting had over 300 poster presentations, where I also got an opportunity to present my work so far and discuss with the best researches in japan and also world-over. It was interesting to discuss with various interesting research projects from japan and other places, also helping understand our own research problems better and flashing some new and interesting insights.

The talks by Prof Eric Wieschaus and Prof Roel Nusse were enlightening and it was really a great opportunity to interact with these scientists, who were very encouraging and made the science more interesting , by inducing many new questions in the mind and also helping our research interests through superlative discussions.  apart from the conference Kyoto as a citywas serene and beautiful, having been to Tokyo this part of the world seemed a page from the ancient and rich traditional Japan and a wholly different landscape from what I had seen or imagined.

People in Japan were very kind, polite, peace loving and sweet who helped in every step of my stay. There a lot of international students around especially in my residence where they were very cooperative and were as kind as Japanese themselves. They organized various events from the art of wearing Japanese yukata (traditional Japanese dress) to that of attending the local city festival on weekends. They helped with every problem and also make stay fun filled and enjoyable in every way.  Cycling was the best transport in Japan for there were free lanes; it was always fun riding to university through a very beautiful park. For being a vegetarian the other constant problem was food, which I had to cook to survive in a land where nothing was vegetarian. The versatile kitchen facility eased out cooking for my survival and sometimes the vibrant community joined in usually watching football worldcup cheering for Japan or South Korea. It was the charm of the place and people around that made problems gradually melt away etching wonderful memories, easing life and making work enjoyable in a very pleasant ambience.

This visit helped move rapid strides in answering my research question and allowed me to learn newer methods to apply and progress in my research work. I am sure a lot of research problems will be solved and this work will raise new and interesting questions for me to pursue further ahead in research. I hope my experience will encourage more people to work across borders to learn the best from all the great learning centers and Japan in particular, which has people who work really hard and help each other to reach greater heights in their endeavors.

I would like to thank the Development and APDBN fellowships for their encouragement and generous support for my travel and stay in Japan. I would like to thank the Prof Fujiwara and University of Tokyo for the kind invite, support and warm welcome into their facility. My sincere thanks to the lab members of his lab and also other labs which helped and supported to the fullest, whose untiring help and encouragement helped me enjoy both work and stay in Japan. I would like to thank my supervisor Prof. Shashidhara and IISER pune for initiating this interaction and supporting all the way in my graduate study. I would like to thank node for allowing me to share my unforgettable memories of  Japan.

(2 votes)

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Here’s an uplifting story about how a farmer and a developmental biologist met online and started a collaboration.

Earlier this month, I attended the annual Science Online conference in London. This year’s speakers included Sir Martin Rees of the Royal Society, former Member of UK Parliament Evan Harris, and a good selection of people who are involved in using the Internet to either communicate or facilitate scientific research.

One of the speakers in several panels was science writer and blogger Ed Yong, of the blog Not Exactly Rocket Science. On the first day of the meeting he spoke on a panel about science journalism, and on the second day he was on involved in a discussion about interacting with your readers online. He gave some good advice there, about communicating with your readers and knowing who they are. In Ed’s case, his audience is very general, including scientists as well as non-scientists, so his readers could very well be anyone.

On Saturday, Ed posted an anecdote that shows exactly how broad his readership is, and what he does to engage them. Since one of his tips at the Science Online meeting was to simply link to other blogs when they write it just so much better, I’ll send you back to his place for the full story, and will just summarize it here:

Several months ago, a paper came out about gynandromorph chickens. To refresh your memory: these chickens are female on one side of their body and male on the other side, and by studying them the group of Mike Clinton in Edinburgh revealed that in chickens sex identity is determined early in development and is autonomous for all cells (rather than being regulated by hormone levels). Ed wrote about the paper on his blog, and recently Paul Sanders, a farmer in Missouri, found that very post when he was looking for information on a curious-looking chicken (pictured left) that was born on his farm. Ed then put him in touch with Mike Clinton, and the resulting e-mail conversation between Sanders and Clinton shows how they’re going to collaborate to further investigate the development of gynandromorphic chickens. Since Sanders has access to the bird as well as the parents of the bird, Clinton can carry out more detailed genetic analysis. According to one of Clinton’s e-mails, Sanders’ observations about the size of the egg alone are already an indication that one of the theories about gynandromorphic development — that these animals originate from eggs with a double yolk — is not likely to hold ground!

It’s good to see the reader interaction that Ed mentioned at Science Online in action, and leading to collaborations in developmental biology! Do you know of any other examples of interesting collaborations in the field? We’d love to hear!

(Image credit: Paul Sanders.)

(4 votes)

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The RIKEN CDB seeks laboratory heads to lead independent laboratories under the following two Programs. Applicants can choose to apply for a specific position, or allow the search committee to assign them to an appropriate position during the course of the evaluation.

1. Position

・Team Leaders (Creative Research Promoting Program)
The CDB is looking for creative young researchers (preferably those who have obtained a PhD within the last 10 years) who aspire to break new ground within areas of animal development and regeneration, and related research areas.
・Unit Leaders (Center Director’s Strategic Program)
The Unit Leader position is for scientists in the early stages of their career to conduct research in a small-scale laboratory. Highly motivated scientists eager to achieve breakthroughs in next-generation developmental biology in the areas listed are encouraged to apply.

2. Selection Process

Research proposals should be focused on the specific field of research for each program. The initial screening process will be based on the applicant’s application and 5-year research proposal. This will be followed by a final selection process, which includes an interview and seminar. Strong emphasis will be placed on the quality, feasibility and originality of the research proposal; priority will be given to proposals that take full advantage of the CDB’s facilities and resources, and advance challenging new concepts. Female and foreign scientists are strongly encouraged to apply.

The selection process will begin November 1, and will continue until suitable candidates have been selected.

Please visit our website for more detail: http://www.cdb.riken.jp/en/index.html

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Hello Node folks.  My name is Kim Cooper, and I’m a postdoctoral fellow with Cliff Tabin at Harvard Medical School.  I recently spoke at the SDB meeting in Albuquerque, and Eva Amsen approached me about contributing to the Node.  The primary reason is because I’m working on a fun animal that takes me off to China for field collections and has sent me down a rough road of learning to breed an exotic in captivity.  The animal is a jerboa.  It’s a bipedal desert rodent related to rats and mice.  They’re native to northern Africa through the Middle East, Central Asia, and northern China.

I’m interested in this adorably bizarre animal because it is an excellent model for evolutionary novelty in the limbs.  They have elongated hindlimbs with enormous feet that have only three toes and metatarsals that are fused into a single bone.  This gives them a long bounding stride upright on their hindlimbs, and they really only use their forepaws for feeding, digging, and grooming.  They are very efficient movers – they can hop three meters in a single leap and a meter straight in the air when startled.

The gist of what I’m doing with these animals involves collecting embryos from pregnant females soon after the come out of hibernation and breed more or less synchronously in northern China. The embryos are fixed and preserved in methanol and then shipped back to Boston for further developmental studies. I’m taking a two-pronged approach by candidate gene analysis and RNASeq to identify genes that are expressed differently in the three-toed hindlimb of the jerboa compared to the five-toed forelimbs and fore and hindlimbs of a near relative – the mouse.

I’m excited to share field collection stories from China and experiences with starting the colony.  The field stories are easy since I’ve been keeping a travel blog for about 5 years now and can cross post from previous years until the next field season starts again in the spring.  So stay tuned.  As a teaser I can tell you I’ve been chased by camel ticks in the desert, slept in a yurt near the border with Pakistan, and come home with typhoid.  But I’ve had some great times and met a lot of wonderful people along the way.  And collected a lot of jerboas.

(5 votes)

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(This interview by Kathryn Senior originally appeared in Development on September 7, 2010)

Ken Zaret is Joseph Leidy Professor in the Department of Cell and Developmental Biology, the Associate Director of the Institute for Regenerative Medicine, and the Co-Director of the Epigenetics Program at the University of Pennsylvania School of Medicine. He agreed to be interviewed by Development and talks about his life as a scientist.

What originally set you on the road towards a career in science?

As a teenager, I loved puzzles of all kinds, and doing science is about solving puzzles. I have also always enjoyed being out of doors. Hiking is one of my favorites, and I originally wanted to be a naturalist; traveling the world and studying different forms of life was really appealing. In high school, I received a fellowship from the National Science Foundation to do research at a medical school in Philadelphia, which exposed me to laboratory science. Then, in college, I had several inspiring biology professors. When I took biochemistry, it all came together and I knew I wanted to do research.

How has your career progressed and what has influenced your decisions about institutions and locations?

When I was 30, I started my own lab at Brown University, which attracts great students, has a highly collegial faculty and, being located near Boston, is part of a larger scientific community. I benefited from the stimulating environment – and I learned developmental biology. After about 13 years, I was recruited to the Basic Science Division at the Fox Chase Cancer Center in Philadelphia. This was a good move for me, as I enjoyed the focus of being at a research institute instead of a university but, after 10 years, Fox Chase began to pursue mainly translational research and I felt it was right for me to move back to academia. I have been at the University of Pennsylvania since then and I greatly enjoy the diverse and active research life that it offers; working there is highly stimulating.
(more…)

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The server that the Node runs on is going to receive some general maintenance between 6:30 PM UK time tonight and early tomorrow morning. This may affect our visitors in North America (and the early risers at the other end of the Pacific) so please be patient if anything seems to not be working during this period.
The down time could be as brief as 30 minutes, and everything should work again on Friday. Thanks for your understanding!

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New format for job postings
You may have noticed some job ads for postdocs appearing on the Node. Until today, these ads appeared with the rest of the posts, but we now changed how job ads are displayed on the Node, to make them stand out from the rest of the content. This makes it easier for people who are looking for jobs to find the ads, and less intrusive for those who aren’t looking for work.

Job ads no longer appear in the main body of the site, with the rest of the posts, but are accessible in three other ways;
-The three most recently posted ads are listed by title in the sidebar (between “recent comments” and “events”) on all pages of the Node. They can also be accessed from the archive in the sidebar
-The Jobs category lists all job ads
-Jobs have their own RSS feed, which can be reached from the page containing all the different feeds on the Node. If you want to receive both regular Node content and job ads, you need to subscribe to both feeds.

Adding an announcement for a job opening in your lab works exactly the same as writing a post. Make sure that you have the title field filled in, and that you select the category “Jobs”. Job postings don’t show up in the main body of the site, but in the sidebar only. There is also a separate RSS feed for job postings.
(The previous paragraph has also been added to the e-mail that new authors receive.)

Finally, the Help page has been updated to reflect these changes.

E-mail updates about the Node
Currently, e-mail updates about new Node posts arrive as a “daily digest”, and will probably still include job ads. It’s also possible to set these updates to occur after every post (which is approximately once per day at the moment anyway) and have users select which categories they would like to receive in e-mail. In that case, if you only want e-mail notifications of interviews, or everything except job ads, you can change those settings.
The choice between digest or per-post cannot be made at the individual user level, unfortunately, so we have to make one decision for everyone. Let us know please, in the comments, what you would like: the option to select which categories to receive in e-mail, OR the daily digest. (In both cases, you have the option to turn notifications off entirely through the WordPress dashboard.)

(2 votes)

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Here are the research highlights from the current issue of Development:

Nr5a receptors reset EpiSC pluripotency

Rodent embryonic stem (ES) cells that are derived from blastocysts self-renew without mitogenic growth factors and robustly colonize chimaeras, whereas egg cylinder-derived stem cells (EpiSCs) require fibroblast growth factor and contribute poorly to chimaeras. Nevertheless, expression of a single reprogramming gene, such as Klf4 or Nanog, can return EpiSCs to a molecular and developmental pluripotent ‘ground state’. Now, on p. 3185, Ge Guo and Austin Smith use a genome-wide genetic screen to identify other molecules that can reprogramme EpiSCs. By using piggyBac transposition to randomly activate endogenous gene expression in mouse EpiSCs and by selecting for undifferentiated colonies in the absence of growth factors, the researchers unexpectedly identify the Nr5a nuclear receptors as potent inducers of ground state pluripotency. Intriguingly, they also show that, unlike previously identified reprogramming factors, Nr5a receptors do not play a role in ES cell renewal. Together, these results highlight the usefulness of EpiSC conversion (in defined culture) as an experimental system for studying molecular reprogramming.

EGFR-Notch signalling makes (proneural) waves

During neurogenesis in the Drosophila optic lobe, a wave of differentiation that converts neuroepithelial cells into neuroblasts sweeps across the neuroepithelial sheet in a medial to lateral direction. This differentiation wave is preceded by the ‘proneural wave’: the transient expression of the proneural gene lethal of scute [l(1)sc]. Now, Tetsuya Tabata and colleagues report that EGFR and Notch signalling play pivotal and coordinated roles in proneural wave progression in the Drosophila optic lobe (see p. 3193). They show that EGFR signalling is activated in neuroepithelial cells and induces l(1)sc expression. Transient, spatially restricted expression of Rhomboid regulates EGFR, they report, and Rhomboid expression is regulated by the EGFR signal, a feedback loop that moves the proneural wave laterally. The researchers also report that Notch signalling, which prolongs the proneural state, is regulated both by itself and by EGFR signalling. Based on these results, the researchers propose that coordinated sequential EGFR and Notch signalling regulates proneural wave progression, which, in turn, induces neuroblast formation in a precisely ordered manner.

Hand2 on heart: promoting cardiac fusion

The embryonic heart tube forms from bilateral groups of cardiomyocytes that move towards the embryonic midline where they merge. The transcription factor Hand2 is essential for this ‘cardiac fusion’ but its downstream effectors are unknown. By studying zebrafish heart development, Deborah Yelon and colleagues now identify Fibronectin as a component of the Hand2 pathway that mediates cardiac morphogenesis (see p. 3215). By performing transplantation experiments between wild-type and hand2 mutant embryos, the researchers show that hand2 regulates cardiac fusion by altering the environment through which the cardiomyocytes migrate. Next, they show that fibronectin 1 (fn1) expression is increased in hand2 mutant embryos. Finally, they report that reduction of fn1 function rescues cardiac fusion in hand2 mutant embryos but not the apicobasal polarity defect that is also seen in these embryos. Thus, the Hand2 pathway regulates cardiac morphogenesis by establishing an appropriate environment for cardiac fusion by limiting Fibronectin function but it establishes the apicobasal polarity that is needed for heart tube extension through another, unidentified, effector.

Wise up to Wnt’s role in tooth development

The number, size and shape of mammalian teeth vary widely – just compare a person’s smile with a dog’s ‘smile’. But what controls the patterning of dentition? Mutations in Wise (Sostdc1), which encodes an inhibitor of Lrp5- and Lrp6-dependent Wnt signalling, cause patterning defects in tooth development in mice. Now, by investigating the pathways modulated by Wise, Robb Krumlauf and co-workers show that crosstalk between Wnt and other signalling pathways controls mouse tooth development (see p. 3221). The researchers use genetic experiments to reveal that Wise suppresses the survival of vestigial tooth buds in the normally toothless region between the incisors and molars by inhibiting Lrp5- and Lrp6-dependent Wnt signalling. They also identify the Fgf and Shh signalling pathways as major downstream targets of Wise-regulated Wnt signalling, and show that Shh acts as a negative-feedback regulator of Wnt signalling. Thus, the researchers suggest, variations in the expression of signalling modulators such as Wise could underlie the evolutionary diversity in mammalian dentition.

Del1-ving into forebrain development

During early embryogenesis, morphogen gradients specify the neural plate along the anterior-posterior axis. Canonical Wnt signalling causes the posteriorization of neural tissues. Consequently, Wnt signal attenuation in the embryo’s anterior region is required for the determination of the head region; but how is this achieved? On p. 3293, Hidehiko Inomata, Yoshiki Sasai and co-workers reveal that modulation of canonical Wnt signalling by the extracellular matrix protein Del1 (Developmental endothelial locus-1) is essential for forebrain development in Xenopus embryos. Del1 overexpression expands the forebrain domain, the researchers report, whereas Del1 functional inhibition represses forebrain development. They show that Del1 function in neural plate patterning is mediated mainly by inhibition of canonical Wnt signalling downstream of β-catenin. Notably, however, Del1 inhibition of canonical Wnt signalling involves the Ror2 (receptor tyrosine kinase-like orphan receptor 2) pathway, which is implicated in non-canonical Wnt signalling. These data suggest that Del1 promotes forebrain development by creating a local environment that attenuates the cellular response to Wnt signals via a unique pathway.

Extracellular signal PARtners asymmetric division

Asymmetric cell divisions generate cell diversity during development, and the orientation of the axis of these divisions determines the future position of differentiated cells. But is the asymmetrical localization of the polarity (PAR) proteins that control asymmetric cell division regulated by extracellular or intracellular signals? On p. 3337, Yukinobu Arata and colleagues answer this controversial question. In C. elegans embryos, the P0 zygote and the P1, P2 and P3 germline cells undergo a series of asymmetric divisions. By examining the development of these germline cells in vitro, the researchers show that, although PAR-2 is distributed asymmetrically in P2 and P3 cells in the absence of extracellular signals, the orientation of PAR-2 localization in these cells depends on their contact with endodermal precursor cells. Other experiments indicate that the endodermal precursor cells control the orientation of PAR-2 localization by extracellular signalling via the MES1/SRC1 pathway. The researchers propose, therefore, that Src is an evolutionarily conserved molecular link that coordinates extrinsic cues with PAR protein localization during asymmetric cell divisions.

Plus…

KNOX genes: versatile regulators of plant development and diversity

Plant KNOX homeodomain transcription factors maintain pluripotent stem cells in the shoot apical meristem, and recent studies have uncovered novel roles for the KNOX proteins in sculpting plant form and its diversity, which Angela Hay and Miltos Tsiantis review. See the Review on p 3153

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Recently a paper in Science caught my attention since its title combines the words mitotic recombination with patients and Ichthyosis. Having worked with Drosophila during my PhD and now being in a vertebrate lab, I’m well aware of the existence of tools to induce mitotic recombination to generate somatic clones of mutant cells in certain tissues. So I had a closer look at the paper to understand more about the spontaneous occurrence of mitotic recombination in humans.

“Ichthyosis with confetti” (that’s what it’s called!), or IWC for short, is a very rare sporadic skin disease. Patients display red skin because their skin barrier is defective and they often die of bacterial infections. The reason the disease carries the word confetti in its name is that in the first year of life, the otherwise reddish body starts to be covered in pale spots, resembling confetti, which increase in number and size with age.

Now it has been found that these pale spots are clones of “revertant” cells arising through mitotic recombination. Most cells in the body of IWC patients are heterozygous for a spontaneous dominant mutation in the keratin 10 (KRT10) gene that causes the red skin disease phenotype. The exact mutation in KRT10 differs between patients, but all of the mutations result in frameshifts in the same alternative reading frame of KRT10. The product of this is an arginine-rich peptide that mis-localizes to the nucleolus and thereby disrupts the keratin filament network of skin cells. The pale clones of revertant cells are formed when mitotic recombination causes loss of heterozygosity in KRT10, so that these clones no longer carry the mutation and therefore behave like normal cells. Reversion to wild type occurs at very high frequency, suggesting a general increase in the rate of mitotic recombination in these individuals. It is not yet known what causes this elevation.

So, what did I learn from this? Mitotic recombination in multicellular organisms is not just a peculiarity that can be useful for experiments in model systems, it also occurs naturally in humans. For reasons still unknown, its rate can be increased when beneficial for the cells affected. Cancer cells appear to exploit this phenomenon, increasing the rate of mitotic recombination to speed loss of heterozygosity of tumor suppressor mutations to promote their survival and growth.

Who knows, one day induction of mitotic recombination to remove undesired mutations might even be used as a therapy in humans, as long as the homozygous mutant sister cells eliminate themselves as seems to be the case in IWC. As always, the frightening part in this scenario is the possibility of losing control and causing unwanted and potentially harmful mutations. We’ll see.

Choate KA, Lu Y, Zhou J, Choi M, Elias PM, Farhi A, Nelson-Williams C, Crumrine D, Williams ML, Nopper AJ, Bree A, Milstone LM, & Lifton RP (2010). Mitotic Recombination in Patients with Ichthyosis Causes Reversion of Dominant Mutations in KRT10. Science (New York, N.Y.) PMID: 20798280

(5 votes)

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“Why are there no pop hits about Arabidopsis?” sings Karmadillo. Even though their Arabidopsis song is not a pop hit (yet?) either, Karmadillo can at least lay claim to the honour of having performed it alongside other science-themed songs on the “Reproductive Stage” at the virtual 2010 Geek Pop festival.

The song celebrates Arabidopsis as model organism, with such lines as: “That the public don’t know you, that’s unfair, but they can get your genome, thanks to TAIR.” The music video also has plenty of lab footage showing Arabidopsis in action:

Rishi Nag, the main man behind Karmadillo, lives and works in Cambridge, so I managed to catch up with him this summer and ask him about the song and how he came about writing it.

Rishi, my first question is maybe a bit obvious, but why are there no pop hits about Arabidopsis?

I think it just never hit the romantic side that roses have. The song that I wrote was meant to be about this plucky little plant that a lot of biology work is being done on.

Why did you write the song?

I work in the Department of Plant Sciences [at Cambridge University] and we had a Christmas revue at the end of the year, where people from various departments were getting together do all kinds of songs. I had the idea to write the song for that, but didn’t get it done in time. Then there was this festival called Geek Pop at the start of the year, and I had some time off over Christmas so I managed to sit down and record it. Having a deadline to submit it for Geek Pop was quite a motivating factor to finish it. [Before that] I think I just had the chorus stuck in my head for a while.

How have people responded to it?

Oh, it’s been really popular, so that’s been really nice. I wrote another song called “Brownian Motion” which is more of a physics song, which I think has been my most popular of the Geek Pop songs, I’m afraid.

How did you get interested in science?

I work in the group run by David Baulcombe, [and] I’m actually a bioinformatician/web designer. Essentially my background was nothing to do with biology, and then a couple of years ago I started doing the website for a pan-European EU-funded project called SIROCCO, dealing with [RNA] silencing in various institutions. Through that I’ve started learning more about bioinformatics, and taking on a bigger role in that. It’s been really interesting and exciting for me. I have a background as a DSP (digital signal processing) software engineer. That’s quite dead scientifically in that what you’re doing commercially is as good as it will get for the most part. Then to come into bioinformatics and learn about genetics and genes just really whetted my appetite again for science and its processes.

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