Many of you are probably familiar with the web comic Piled Higher and Deeper (PhD), which chronicles the lives of graduate students and perceptively points out some of the peculiarities of academia. Recently, we met up with the comic’s creator, Jorge Cham, and talked about graduate school, recognizable academic situations that cross all disciplines, and procrastination.

(Thanks to Node readers Kat, Pablo, and Sandra for providing some of the questions.)

When did you start drawing Piled Higher and Deeper?

I started during my first term in grad school, so I was definitely not supposed to be drawing comics. I was a teaching assistant, I was a research assistant, I was taking classes – but I saw this ad in [The Stanford Daily] newspaper calling for comics, and I just thought I would submit something nobody had ever really written about or made fun of: people trying to get their PhDs.

How did you manage to find time to combine that with grad school itself?

I didn’t sleep a lot during that semester! But I started publishing a new comic five days a week, and that quickly became only three times a week.

Many of your readers, including myself, grew up with your comic throughout grad school. Meanwhile, some of us have graduated, but a lot of your characters still haven’t. Are they ever going to graduate?

Yeah, the series will not go on indefinitely. I definitely have endings or events for all of the characters, whether they graduate or not.

Will there be a spin-off postdoc comic then?

Heh! Well, they might become postdocs. One of the characters is now a postdoc, but it will probably still be called “Piled Higher and Deeper”

We noticed that the comic works well for a lot of different fields. The readers of the Node are all developmental biologists, and you don’t have a biologist character in the PhD comics, but a lot of the things are still recognizable. Do you notice that a lot of the situations you write for, for example, the engineer characters are applicable to any field?

I do it on purpose. When I first started grad school I happened to know a lot of people who were in many different fields: Anthropologists, economists, engineers, geophysicists – and they were all friends! Just listening to them I could tell that they were all sharing the same experience. So for me, from the very beginning that was something that was interesting to me, so that’s the way I wrote the comics. I grounded the characters in a specific department, so that there’s a bit of realism there, and you get the sense that they are doing something. But I try to write the dialogue so that it generally speaks to academics and grad students in all disciplines.

That being said, there are specific things that biologists have to deal with that don’t occur in other fields, like the fact that you have to take care of living things on the weekend. Has anyone ever requested a biologist character?

Yeah, a lot. In fact, I’m very familiar with the idea of being beholden to experiments like that, because I worked in a neuroscience lab for two years. Somebody once described it as “your life being run by the menstrual period of rats”. I have a character who is going to focus on biology, but probably not for another year or year-and-a-half.

You also travel around to give talks about procrastination. A lot of visitors to the Node drop by during a break from work, and I’m sure they’d like to know if there’s any value to procrastination.

I don’t like to talk about whether procrastination is good or bad. I just like to talk about the fact that you do it, and that you probably do it for a reason. There’s a lot of flexibility in grad school, and it always feels like it never ends. There’s always something more that you could be doing – something more that you should be doing –so a lot of times people find themselves procrastinating. What I like to say is that procrastination is not necessarily bad, but that it’s sometimes an important part of the creative process, and can reveal what you really want to do, and what your real passions are. If you find that you’re not spending as much time as you should be on, for example, writing this particular chapter for this particular professor, it maybe means that you don’t really want to write it. Instead of feeling bad about it, you should just realize it, and focus on something else.

Finally, one of our readers in South America asked when you’re coming to the Southern Hemisphere

You just have to invite me – that’s pretty much how it works!

Part of a collection of panels Jorge drew at Sci Foo, where we met for the interview.

Part of the interview in audio format:
[audio:https://thenode.biologists.com/wp-content/uploads/2010/08/jorge-cham.mp3|titles=jorge cham]

(6 votes)

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(This interview by Kathryn Senior originally appeared in Development on August 10)

Shin-Ichi Nishikawa is Group Director of the RIKEN Center for Developmental Biology in Kobe, Japan, where his stem cell research focuses on understanding the mechanisms involved in cell differentiation. He joined Development as an editor in 2009. We interviewed Shin-Ichi to find out about his interest in developmental biology, about the event that made him change career from being a practicing physician to a researcher, and his current research interests.

Looking back, when do you first remember being interested in science?

This was quite early in my life, when I was still a pupil at elementary school. I remember very clearly the day that the Sputnik satellite was launched by the Soviet Union – on October 4, 1957. I heard the news and was amazed that something the size of a beach ball had been sent into orbit around the Earth. We didn’t know it then, but this was the dawn of the space age, the beginning of the space race and the start of my life-long passion for science.

What path did you follow in your early career?

I was desperate to work in a scientific field but I was not good at maths or physics, so becoming a researcher in physics or space technology wasn’t really an option. I decided to study medicine and got my MD at the Kyoto University School of Medicine in 1973. I then worked as a chest physician for about 7 years, completing an internship and residency at the Kyoto University Chest Research Institute. My plans at that stage were to carry on in medicine, and I would very likely have stayed on track if I had not caught hepatitis when treating one of my patients.
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The Bicoid gradient, epigenetic control of BMP signalling, haematopoietic stem cells and more…here are the highlights from the current issue of Development:

The Bicoid gradient gets into shape without nuclei

Morphogen gradients provide key positional information during embryogenesis but how they are established is not well understood. A gradient of the transcription factor Bicoid is known to provide Drosophila embryos with positional information along their anterior-posterior axes. Since Bicoid is enriched in nuclei, nuclei have recently been proposed to act as potential traps or sites of degradation that could slow down Bicoid diffusion from the anterior pole and hence contribute to the observed Bicoid gradient. On p. 2857, Oliver Grimm and Eric Wieschaus address this issue experimentally and find that the Bicoid gradient is shaped independently of nuclei. Using mutated Bicoid with impaired nuclear localisation, they show that the resulting gradient of this protein is indistinguishable from that formed by normal Bicoid protein. They also show that the initial centre-to-surface redistribution of Bicoid and the scaling of the gradient are not influenced by Bicoid nuclear accumulation. Based on these findings, the authors propose that nuclei do not play a role in shaping the Bicoid gradient.

Spinal cord development BuMPs into epigenetics

During spinal cord development, transcription factors and signalling proteins, such as the BMPs, are involved in neural tube (NT) patterning and in inducing neural differentiation. Although epigenetic modifications are known to regulate the expression of key neural development genes in stem cells, whether they have a role in spinal cord development remains unclear. On p. 2915, Marian Martínez-Balbás and colleagues study histone H3 lysine 27 trimethylation (H3K27me3) in vivo during chick embryo neurogenesis. They show that global levels of H3K27me3 increase along neurogenesis and regulate BMP signalling within the NT. Using microarray analysis, they find that the expression of Noggin, a BMP inhibitor, is repressed by H3K27me3. Importantly, they show that, in response to BMP activity, the histone demethylase JMJD3 interacts with the Smad1/4 complex to demethylate and thereby activate the Noggin promoter. This reveals a novel pathway by which BMP signalling can regulate its own activity within the spinal cord by modulating expression of its inhibitor Noggin.

microRNA regulation of Hox genes: RNA tails matter

The Hox family of transcriptional regulators plays a central role in specifying segment identity along the anteroposterior axis of animal bodies. The Drosophila Hox gene Ultrabithorax (Ubx) is dynamically expressed during development and controls the development of posterior thoracic and anterior abdominal segments. On p. 2951, Claudio Alonso and colleagues show that during development the Ubx gene produces multiple transcripts that vary in their visibility to microRNAs (miRNAs). They demonstrate that different parts of the embryo express Ubx transcripts that contain variable 3′ UTRs, each harbouring a distinct set of miRNA target sites. The differential distribution of these transcripts during development is independent of miRNA-mediated degradation but is instead due to an in-built system that processes mRNAs according to developmental context. They also show that other Hox genes, such as Antennapedia, abdominal-A and Abdominal-B, exhibit similar developmental RNA processing and propose that developmental processing of 3′ UTR sequences is a general molecular strategy that allows spatiotemporal control of mRNA-miRNA interactions during development.

Haematopoietic differentiation: lessons from development

Efficient production of haematopoietic stem (HPS) cells from embryonic stem (ES) cells or from induced pluripotent stem (iPS) cells requires a thorough understanding of haematopoietic differentiation pathways. On p. 2829, Gordon Keller and colleagues show that generation of HPS cells from ES and iPS cells follows the same steps as haematopoietic development in the embryo. They induced ES cells with known agonists of embryonic haematopoiesis (activin A, BMP4 and VEGF) and identified two temporally distinct populations of cells expressing the haematopoietic marker Flk1. The gene expression profiles, cell surface markers and lymphoid potential of the early Flk1-positive population resemble those of the first site of embryonic haematopoiesis, whereas the cells that expressed Flk1 at a later stage correspond to a later stage of haematopoiesis. The ability to identify and isolate different stages in the progression from ES or iPS cells to HPS cells will facilitate the study of the generation of blood cell lineages and might improve the efficiency of production of transplantable cells.

Branching out: strigolactones modulate auxin transport

Shoot branching in plants occurs after bud activation in axillary meristems, which are stem cell clusters along the shoot. This process is repressed by strigolactones by a poorly understood mechanism. One model suggests that strigolactones do not act on the bud directly, but inhibit shoot branching by preventing auxin transport out of the bud. Ottoline Leyser and co-workers now show, on p. 2905, direct evidence in support of this model. The researchers treated Arabidopsis stem segments with a synthetic strigolactone, GR24, and found that this reduced auxin transport. Furthermore, they ruled out a direct effect of strigolactones on bud growth by showing that treatment of a solitary bud with GR24 alone had no effect on bud outgrowth, but that GR24 increased the inhibitory effect of an additional auxin source. In addition, they demonstrated that GR24 enhanced competition between two buds on the same stem. Collectively, these data support the model that strigolactone inhibits shoot branching by regulating the efflux of auxin from axillary buds.

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I’ve just come back from a lab retreat in a country house in Sussex, UK. The weather was good and we had our scientific sessions, ranging from discussions on Sonic Hedgehog signaling in the neural tube to the latest super-resolution imaging techniques, outdoors in the courtyard. However, every once in a while, we would be interrupted by a group of white peacocks.

We thought they were albinos, but once I was back in London I did some research and found that white peacocks do not necessarily have a defect in pigment formation, as is the case for albinos. The feathers of peacocks (and several other birds) acquire most of their iridescent color by using optical phenomena such as interference, diffraction and scattering of light. This property is known as structural color and for peacocks it results from way the nanostructure of their feathers interacts with light. For different colors, these different nanostructures are on the scale of the perceived colors’ wavelengths. White peacocks seem to have an altered nanostructure in the barbules (secondary branches) of their feathers.

The birds intrigued me and I wanted to find out how the nanostructure of white peacock feathers is different from the more colorful varieties. However, I couldn’t find anything on this (Does anyone know? Please comment!). Instead I came across something else that took me in a different direction: The development of dinosaur feathers.

How do you study the development of a dinosaur? The obvious way is to compare a younger and an older fossil of the same species, and in China, Xu and colleagues have done just that. They discovered two juvenile specimens of the oviraptorosaur Similicaudipteryx. One is younger than the other and the structures of specific wing and tail feathers differ dramatically between the specimens: Those of the younger one have a ribbon-like structure proximally, whereas the older specimen displays longer feathers without ribbon-like features. This was unexpected because in modern birds, feather morphology does not change after hatching. The researchers concluded that Similicaudipteryx might have undergone molting of feathers at some stage after hatching. Of course, molting takes place in modern birds but it doesn’t result in such severe changes in morphology.

So far, so good. But what really struck me were their speculations about how this change in morphology might have been taking place molecularly. In modern feathers, bone morphogenetic protein (BMP), noggin and sonic hedgehog (SHH) regulate the formation of the different feather components. SHH induces apoptosis between the barbs (primary branches) of the feather. Without SHH, a continuous, ribbon-like structure would form, which is probably what happened in the proximal part the younger dinosaur’s feathers. Xu and colleagues speculate that in Similicaudipteryx, the induction of SHH and other barb-specifying genes were delayed compared to modern birds, where these genes are strongly expressed during the growth of even the earliest feathers. SHH, the regulator of neural tube patterning I deal with every day is thought to have a role in the development of strange dinosaur feathers!

If only we could make a transgenic dinosaur. Then again, maybe not.

(7 votes)

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Today is the first day of the SDB meeting in Albuquerque. The program looks amazing, and I’m looking forward to many of the talks. The meeting is held jointly with the Japanese Society for Developmental Biologists, so many of the attendees came all the way from Japan.

Development and the Node are here in Albuquerque as well. You can find us at the Company of Biologists booth as well as in the audience at the talks.

We hope to summarize the meeting on the Node afterward, but could use some help, because try as we might, we can’t be everywhere at once! So if you’re at the SDB meeting, and would like to help us out by summarizing part of the event for the readers of the Node, please get in touch. You can leave a comment here, send an email, or track me down in person. We ask, at this particular meeting, that you get in touch before writing, because we’ve agreed with the conference organizers to write a report the “old fashioned way” on the Node – meaning that speakers’ permission will be asked before posting the report. If you want to write something, please do let us know and we’ll contact the speakers for you.

Here are some reports from previous society meetings on the Node:
– BSDB/BSCB meeting part I, part II, part III
– SFBD/JSDB meeting
– ISSCR meeting
See also our general tips for blogging from meetings.

I’m looking forward to an interesting meeting, and hope to see some of you here!

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Model organisms never looked so delicious… The baking blog Not So Humble Pie features science cookies made by the author or by her fans. Many of the cookies are biology-themed, and I think the model organisms are my favourites.

These zebrafish have edible glitter on them to give them that familiar fishy shine

wild-type Drosophila cookies

Of the fly-cookies, the baker-blogger writes “I found it hard to balance a realistic look with something you’re supposed to want to eat.”

But the cookies are not just animal-shaped. Creative tricks with different kinds of icing can make square cookies look like agarose gels and turn round cookies into a tasty plate of bacteria. Yum!

For more biology cookies, visit the science section of Not So Humble Pie. Her own cookies all come with the recipe so you can try making your own at home.

(4 votes)

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Imagine an ordinary louse. You might be thinking of the small insects that infest the human scalp and cause intense itching. What you may not know: lice actually exist on great variety of birds and mammals. Even whales have ‘lice,’ which are not closely related to human head lice and are giant in comparison (can be over 25 mm long!), but these lice do have a similar lifestyle to the common head lice. Whale lice are amphipod crustaceans that exist as ectoparasites in the folds of the whale’s skin and feed on dead skin and debris. Below is a photo of an adult whale louse, almost 2 cm long.

As a student in the MBL’s Embryology class, I had the unique opportunity to get a close look at embryonic whale lice. Whale lice brood developing embryos in a brood chamber called a marsupium. Thus, they have no free-swimming stage and spend their entire life on the whale. Whale lice (Cyamus ovalis) collected from a beached whale were procured from Jon Seger and Heather McGirk of University of Utah for the course. In class, we dissected out embryos from the marsupium of two gravid females. Using techniques and materials provided by the course, we looked at expression of developmental patterning genes by floursecence immunostaining. See confocal stack below with DAPI (nuclei) in teal, phoso-histone H3 (mitotic cells) in magenta, and HRP (neurons) in orange.

(7 votes)

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It’s not often that the introductory part of a research talk is beautiful as well as informative, but Hans Clevers achieves both by using this video about the intestinal crypt in his presentations. (Click either screenshot to see the video)

The video shows how stem cells at the base of the intestinal crypt produce the epithelial cells of the intestines, and how the cells are pushed up toward the tip of the villi. Once at the top, the cells die, but are immediately replaced by the next cells. It’s a “clonal conveyor belt”, constantly moving new cells up.

When Clevers’ lab identified crypt base columnar cells as the stem cells responsible for the generation of the rapidly renewing intestinal epithelium, they simultaneously identified the gene Lgr5 as marker for intestinal stem cells. Until their discovery, other groups had used the method of detection the retention of labeled DNA, which suggested other crypt cells as stem cells.

The last part of the video shows how they used the unique expression pattern of LGR5 to create a knock-in mutant in which the tumour suppressor APC is no longer expressed in stem cells, and show that this is sufficient to trigger adenoma formation.

Clevers had the animation made through a company called Digizyme, which specializes in multimedia approaches to present scientific information. It’s a very welcome addition to the home-made powerpoint slides that you usually see in talks, and I appreciate the effort made to pack this information on intestinal stem cells in an, if you’ll pardon the pun, easy to digest format.

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(10 votes)

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A few bits of news and reminders about the Node, just to keep you all up to date:

-We’ll be interviewing Jorge Cham, creator of the grad student comic Piled Higher and Deeper (PHD), this weekend. Do you have any questions you’d like to ask him? I asked for input via our Twitter account, and have one question so far (plus my own). I’m sure many of you are familiar with the comic, and this is your chance to ask away, so leave a comment with your question!

– Ah yes, the Twitter account. All the bits of news we find that are too short for a proper post end up there. You can follow us if you have a Twitter account yourself, or just look at the page to see what’s there and stay even more up to date than you already are.

– For example, we spread the word on Twitter that EMBO is looking for official bloggers for their annual meeting in September. They ask that you are already registered for the meeting and contribute to an existing blog, but that can be a group blog, like the Node. So if you don’t have your own blog, but would like a chance to blog for EMBO, make sure to register for the Node before you apply. If you’re selected as official blogger, they provide you with direct access to the speakers for interviews, and you receive free registration at next year’s meeting. EMBO’s application deadline for bloggers is August 15. Good luck!

– Finally, you may have noticed comments on the Node disappearing and then reappearing. This is the result of a too sensitive comment reporting system. We’re working to get this solved by the end of August, and will keep you updated about any changes.

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