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Nov162015

Serendipity in the Age of Search Engines:Biology in 3D

Milka is the Senior Editor of Chemistry & Biology and Structure.

I’ve always loved reading—one of the biggest punishments I ever got from my mother was for going to the library without permission.

My mom was at work, my dad on a business trip, and my younger sister at day care. I knew that my aunt was picking my sister up and bringing her home, and that she might arrive any minute, but I just couldn’t wait. The problem was that my aunt did not have the key to our apartment, and if I left, there wouldn’t be anyone to let her in. As this was all happening before mobile phones and text messages, I did the only thing I could: I left my aunt a hand-written note that the I’d gone out and that the key was under the door mat, and attached the note to the door.

I was so eager to get a new batch of books that it never crossed my mind that it might not be the best idea to leave a note that the key to our apartment was under a door mat and attach it to the very door! In the end nothing happened—I got my books, my aunt and my sister got into the apartment just fine, and we were not robbed. But I was still severely punished, as my mom did not appreciate this amount of independence in an eight year old. My aunt continued to joke about this and for decades would say “The key is under the door mat” to many of my brilliant ideas.

This and a few other misadventures along the way could not change who I am—an avid reader. The only thing that changed over the years is what I read. The largest shift happened when I entered college and decided to focus on science. At that point, large volumes of fiction and poetry were replaced by scientific literature, and although over the years fiction, and to a lesser extent poetry, came back into my sphere of reading interest, scientific literature still occupies most of my attention.

In my previous post I talked about how the way I read scientific papers changed as I transitioned from being an active scientist to a scientific editor. One thing that did not change, however, is the way I like to read when I have the luxury of a few moments of spare time. What I enjoy the most when it comes to reading is casting a wide net—going from a single sentence, or that one reference that captures my imagination, and following the trail of ideas and insights to wherever they lead. My starting point is often something that I know a lot about, but I also love starting from a chance glimpse that sparks my curiosity, and digging in.

You hear a lot about serendipity in science, and how unexpected discoveries go on to revolutionize entire fields. As with everything, a bit of it is part of the scientific lore, but anyone who ever did scientific research will tell you that this is actually true—the unexpected happens every day in little ways and does push forward science and our understanding of the world around us. You may also have heard laments of scientists of a certain age who remember going to the library, browsing journals just for browsing’s sake, getting immersed in an article just because, and walking away with a new idea that changed the direction of their research. In their view, serendipitous reading was made obsolete by search engines, online publishing, and keywords.

I am not convinced that the circumstances are as dire as that. A decade and a half ago you could still see me in the library, holding a pile of print issues of different journals in my hand, browsing, reading, re-reading, and flipping around. And sure, that did often lead to something interesting and unanticipated. But today is no different, except that the cozy chairs in the library have been replaced by a standing work station, and the source of initial inspiration comes from more places than a library shelf. These days more often than not my curiosity is nudged by something I see on social media. A simple tweet can snowball into an hour of intense reading and researching through scientific literature now at my fingertips. For me this no different from the good old library days, and the ideas or shift in perception that results from this process is no less valid or powerful than before.

The main enemy of serendipity is not search engines or keywords or social media—it’s the lack of time. So perhaps when people complain about not being able to freely browse and let their explorations of scientific literature go where they may, it’s really nothing to do with digitization of the content, or the fact that we might be too narrowly focused because all we do is use keyword searches. It’s all about the time pressure that we all feel and the need to get to our answers instantaneously.

At the end, you get what you pay for—and paying for a bit of serendipity with an hour of time is worth it to me. Sure, the work does not get done, or the house does not get clean, but in my world serendipity in literature discovery is still alive and here to stay. And I bet there are many of you out there feeling the same way! The main reason I say this so emphatically is that I believe we all, given an option and a blank sheet of mental paper, enjoy letting our minds go wherever they like, allowing ideas and thoughts to float and bounce. This seemingly aimless journey docks us at cognitive islands where treasures are buried, ready to be dug up. This thrills us to bits—and that’s what serendipity is all about.

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Nov132015

Contact, connect and fuse: An ultra-structural view of the muscle formation process

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-By Anusha Krishnan,NCBS

For an avid exerciser, a muscle pull or tear is a painful and fairly common occurrence. A sudden turn or an unusually vigorous bout of aerobics can leave one with a muscle tear that will effectively confine a person to bed for a few weeks. However, muscles do heal – a set of quiescent cells called myosatellite cells in muscles are activated by injury to divide and form myoblasts, which in turn fuse with muscle cells to repair damaged muscles. The mechanistic basis of myoblast fusion with muscle fibers is now clearer thanks to recent work from Vijayraghavan’s group at the National Centre for Biological Sciences (NCBS).

Nagaraju Dhanyasi from Vijayraghavan’s group, has collaborated with Prof. Ben-Zion Shilo and Dr. Eyal Schejter at the Weizmann Institute of Science, Israel, who are also investigating the processes governing myoblast fusion in flies and mice. To study the process at a high resolution, it was necessary to generate electron microscope (EM) images. This allowed researchers to reconstruct the steps in the dynamic process of myoblast fusion, where the structure of the fusing membranes was closely examined. The work involved molecular biology and state-of-the-art electron microscopic techniques, which were carried out in collaboration with the EM facility of the Weizmann Institute. The team’s investigations have resulted in a description of the events during the merging of individual myoblast cells with muscle cells, and was published in the October issue of the Journal of Cell Biology.

Most of our knowledge about the fusion of myoblasts to form multinucleate muscle fibers has been gleaned from studies on the development of tubular muscles of Drosophila larvae. However, the mechanisms governing myogenesis (formation of muscle fibres) in striated muscles of the skeletal musculature in vertebrates is not very clear. This study focuses on the events occurring in myoblast fusion in Drosophila during the formation of flight muscles. These muscles serve as a particularly attractive model, since their developmental program, and their muscle fibre organisation resemble key aspects of vertebrate skeletal myogenesis.

“This work is actually a continuation of studies carried out by Vijay’s earlier students – Priyankana Mukherkjee and Rajesh Gunage”, says Nagaraju Dhanyasi, the first author of the paper. “Priyankana began this work by investigating the role of various fusion proteins using confocal microscopy in the myogenesis of flight muscles of Drosophila. This work was also a collaboration with Drs. Shilo and Schejter. Rajesh established the presence of stem cells in Drosophila muscles similar to the satellite cells in vertebrate muscles. This set the stage for addressing questions on vertebrate muscle regeneration in a Drosophila model system.” The advantages of using Drosophila as a model are many – the tiny fly is easily grown and is amenable to a huge array of genetic manipulations. In spite of this, the study of myogenic processes in flight muscles has lagged behind, primarily because tools for the genetic manipulation of later developmental phases were lacking. “With the advent of RNAi technology, this problem was solved, and we were able to study the myoblast fusion process in great detail”, says Dhanyasi.

The study shows that the fusion of myoblasts to existing muscle fibres, called myotubes, follows a set of distinct stages that requires communication between transmembrane elements and the actin cytoskeleton. An elegant series of experiments allowed the researchers to delineate the ultra-structural details of a series of discrete steps in this event. The process begins with myoblasts binding to the surface of an existing myotube with the help of a host of cell adhesion proteins, a process known as apposition. Following apposition is a flattening of the myoblast membrane to increase its contact surface with the myotube. This step has been shown to require elements of the cell cytoskeletal machinery. The third step in this process is a crucial one where the myoblast membrane and the myotube surface are brought very close to each other in a condition known as ‘tight apposition’. The tight apposition forms multiple areas of cell-to-cell contacts called ‘nascent pore sites’. These contact areas form fusion pores, where the cell membranes of the myoblast and myotubes merge. The fusion pores eventually expand until the myoblast is fully incorporated into the growing myotube.

Future studies are likely to involve detailed investigations on the mechanisms of fusion pore formation and in discovering the molecular players involved in pore formation. “We believe that the cellular and molecular mechanisms uncovered in this study, and in future studies are highly conserved, and therefore also applicable in vertebrate systems. This study is therefore likely to provide key insights into understanding muscle development and repair processes”, says Dhanyasi.

The paper titled “Surface apposition and multiple cell contacts promote myoblast fusion in Drosophila flight muscles” can be accessed here.

Nov132015

How the Way I Read Papers Has Changed Over Time:Biology in 3D

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Milka Kostic

Milka is the Senior Editor of Chemistry & Biology and Structure. She spends her days thinking about structural biology, chemical biology, and the role of her journals in advancing science and serving their communities. She is known to gush about the breathtaking beauty of structures and admires elegant approaches to answering nature’s mysteries. Milka enjoys a good story, scientific or otherwise, especially those with a quirky twist.

“How many papers do you read every day?”

As an editor of a science research journal, I get asked this question a lot. It’s hard to give an exact answer, but between the manuscripts I handle in my journals and the papers published elsewhere that I check out, it can be as many as ten—sometimes fifteen—per day.

The average is probably closer to about five, and I actually don’t know if that’s a lot or a little. If you asked me to guess, I’d say I read twice as much as I read when I was in the lab and actively engaged in my own research. And yet, this increase in volume is not the most important or even the most noticeable change that happened over the years and as I moved from the lab bench to the editorial desk. It’s how I read papers that has undergone a profound transformation.

One change happened relatively quickly as I transitioned from being a scientist to being a scientific editor. As a scientist working in the lab, I spent most of my time focused on the problem at hand, and this often came down to very specific issues either relevant to experimental design or data analysis. Because of the technical nature of my problems, I focused a great deal on dissecting papers I read, especially focusing on experimental design, protocols, reagents, and the data. When I became an editor, my focus shifted from looking for how and what to looking more for why, and since I started handling papers that did not focus on topics I’d encountered much in the past, I started paying very close attention to all the components that help a reader place the how and what into a broader perspective of why and what next. Today, I find that most of my attention is focused on the Introduction and Discussion of a paper since I look to form an opinion about whether a study would be of interest to the broader structural biology community.

Another aspect of the shift from being an active scientist to being a scientific editor is that, as a scientist, I read a great deal looking for ideas and insights that would inspire me, nudge my thinking into a different direction, or cast an alternative light on the data I had in hand. As an editor, I continue to be inspired by what I read, but in papers that I’m handling, I’m also trying to put myself in the shoes of those still actively engaged in research and ask whether they will find anything in the articles I decide to publish to inspire them and make a difference in their thinking and the way they do science.

The other change happened gradually and almost unconsciously. One of the most prominent features of my desk back when I was in the lab was paper—piles and piles of printouts, most of them with elaborate, color-coded markups and notes scribbled all over. I had colorful highlighters and pens all over the place, to the point where I’d actively look forward to visits to the local art supply store to get new writing implements. All this made my reading more enjoyable and my printouts quite colorful. This was also the strategy I implemented when I started as an editor. But gradually, I realized that reading on the screen and making electronic notes makes my life several orders of magnitude easier and my work more portable. I can now lay my hand on any manuscript at any time and any place, marked up and ready to share in a blink of an eye. I also don’ miss making trips to the printer, figuring out that there is a paper jam or that the color ink has run out, and resending my print job once. Or getting half way home just to remember that I forgot to bring all the papers I wanted to go over with mew. Or being at a scientific conference in a remote location and realizing that I left a critical set of notes at home thousands of miles away. I don’t even miss not having a dazzling display of colorful highlighters on my desk.

Perhaps the key reason why I was able to let go of the urge to print everything is because my priorities and interests went from those of someone who was invested in building a deep understanding of a specific scientific topic and becoming a domain expert in a relatively narrow field to someone who has a different knowledge needs, where breadth wins over the depth. That’s a possibility, given that there is a research that suggests that we understand and retain information better if we read from a source that is printed than when we read from screen. But, even if that is the case, I’m quite sure that the days when I print things out in order to read them and understand them are over. I’m also sure that the way I read papers now will continue to change, so I’ll end on a philosophical note: Panta rhei!

Nov132015