Author: Emma Ganley

How Do Flies Fly?


It’s time to give some thought to how a blowfly, or actually any flight-capable creature flies. We circle back to physics here–drag, lift, thrust, and the weight of the creature as key factors. Calculation of the power required–and how to generate that power–is theoretically easier for mechanical flight, but understanding how muscles and their articulations function together in living organisms to overcome gravity, to propel and turn insects, and to sustain them in flight presents more of a challenge. And if you’ve not thought about it before, flies are pretty incredible–they can pull off amazingly nimble, dexterous and swift turns mid-flight that appear to defy their weight, bulk and the relative size of their wings.

Well, ponder no more… In some absolutely stunning research presented in a PLOS Biology paper, Graham Taylor and colleagues have captured in vivo, in living flies, the dynamic internal mechanics of the blowfly wingbeat. They use time-resolved X-ray microtomography to visualize the muscles and hinges in three-dimensions. The method captures cross-sectional images of the fly that can be combined to construct a virtual model of the dynamic movement of each of the muscles and hings through the course of the wingbeat:



The movie is just incredible; this new approach captures the motion of the thorax, the wing power and steering muscles and the hinge. It allows insight into how the fly manages its speedy turn-on-a-dime/sixpence evasive maneuvers that can be simultaneously annoying and impressive when they’re buzzing around.


It’s clear that this has been an exciting project for all involved; when asked about the research, senior author Graham Taylor commented that:

“This has been an awe-inspiring project on so many levels, not least the exquisite complexity of the insects themselves, but seeing the 3D movies render for the first time was one of those breakthrough moments that as a scientist I’ll never forget. It’s a great example of what interdisciplinary collaboration can achieve – facilitated by a longterm development by the beamline scientists at PSI, sparked off by an idea of the insect physiologists at Imperial, and brought to fruition by the members of the Animal Flight Group at Oxford.”


For more information please do take a look at the research article itself and the related primer, both just published in PLOS Biology.

And for more blowfly porn in vivo flight reconstructions here are the other movie files from the research article:



Walker, S., Schwyn, D., Mokso, R., Wicklein, M., Müller, T., Doube, M., Stampanoni, M., Krapp, H., & Taylor, G. (2014). In Vivo Time-Resolved Microtomography Reveals the Mechanics of the Blowfly Flight Motor PLoS Biology, 12 (3) DOI: 10.1371/journal.pbio.1001823

Category: Biology, Biotechnology, Computational biology, Image, PLOS Biology, Video | 3 Comments

Opening Up Data Access, Not Just Articles


Illustration credit: Ainsley Seago.

For those who’ve been paying attention, you’ll have noticed that we just published an interesting Perspective in PLOS Biology from Dominique Roche and colleagues that provides some practical hints on how to improve public data archiving for scientific research.

And if you’ve been even more on the ball, you’ll also have seen the recent announcement of PLOS’ new Data Policy and subsequent Update on the PLOS website.

The new Data Policy will be implemented for manuscripts submitted on, or after, March 1st. The main change is that all PLOS journals will require that all manuscripts have an accompanying data availability statement for the data used in that piece of research. We’re well aware that this may prove to be a challenge, but we think that this thorny issue needs to be tackled head-on. Ultimately, an Open Access paper for which the underlying data are not available doesn’t make a whole lot of sense.

Roche and colleagues raise some important and interesting points in their perspective and do a fine job of detailing the benefits to the scientific community of making data available. But for the eagle-eyed you’ll note an incongruity between their suggestion that a longer embargo period might be necessary before data need to be made available for some subjects, while the PLOS policy won’t make that distinction.

We don’t all have to agree here, and for the short term this may mean that some choose to send their research somewhere that permits them to keep their data under wraps. But funding agencies are also moving more towards our viewpoint, implementing requirements that data be made available. Whether researchers like it or not, this is something that needs to be addressed; it’s time to start ensuring there are better lab, university and institution practices for the storage and archiving of pertinent data.

If what we really want to see is optimal advancement of science, then open access to research means open access to as much as possible associated with the paper and not just the paper itself.  What should such openness include?  Well – probably everything – from methods to code to materials to equipment.  But without a doubt a key component of openness is access to the data behind a study.  Access to data facilitates reproducibility and testing of a papers conclusions and methods and also enables new discoveries to be made without the expense of redoing the experiments.   We believe that the more open we all are about open data, the more we discuss the benefits and challenges,  and the more we shift the bar towards openness, the better off all of science will be.


Roche DG, Lanfear R, Binning SA, Haff TM, Schwanz LE, et al. (2014). Troubleshooting Public Data Archiving: Suggestions to Increase Participation. PLoS Biology, 12 (1): e1001779. DOI: 10.1371/journal.pbio.1001779


More posts on PLOS Biologue about data:

“Dude, where’s my data?” by Roli Roberts

“Improving data access at PLOS” By John Chodacki

“Dealing with data” by Theo Bloom


Category: Biology, Data, PLOS Biology | Tagged , , , | 18 Comments

From Jellyfish GFPs to Plant MiniSOGs; a Microscopy Revolution.


Modified logo wth textI’m a firm believer that a picture tells a thousand words, and in biomedical sciences advances in microscopy can only add to the story that every captured image can portray. As we work through the big reveal of our top ten papers, the biological resolution made possible by the advance detailed in this next paper honestly just astounds me in its physical capacity. The resulting overwhelming beauty of what we can image is awesome, and as a Brit who used to live in the US, I don’t use that word lightly.

State of the art, more than three hundred years ago; Hooke's microscope from his "Micrographia".

State of the art, more than three hundred years ago; Hooke’s microscope from his “Micrographia”.

The problem with microscopy, from Hooke and van Leeuwenhoek onwards, is that most living things are inconveniently transparent. That is, photons (for light microscopy) or electrons (for electron microscopy) tend to pass through tissues without breaking a stride, lending very little contrast to the picture. So many crucial advances in microscopy have involved developing ways of staining tissue samples to enhance their interaction with light or electrons.

But what if you want to see specific proteins, instead of cells or organelles? The ingenious exploitation of antibodies opened up the fields of immunohistochemistry, immunofluorescence and immunoelectron microscopy, but these all suffer from the problem that you’re staining the tissue after it’s dead. Back in the 90′s, Roger Tsien and colleagues developed a way of engineering genes so that their protein product was spliced to a jellyfish protein, green fluorescent protein (GFP). When looked at under a high powered microscope those specific proteins (and nothing else) would glow green. GFP has since been used in tens of thousands of studies, and earned Tsien a share in the 2008 Nobel Prize for chemistry.

In 2011 Tsien published in PLOS Biology an analogous tagging system for protein visualization by way of electron microscopy (EM).  These tags are called miniSOG (mini-Singlet Oxygen Generator – I won’t go into much detail, read the paper for more info), and were obtained by re-purposing and mutating a plant protein called phototropin. The miniSOG tag is half the size of GFP, and not only fluoresces (allowing it to be seen in fluorescent light microscopy), but if you zap it with blue light, it generates a highly reactive chemical called singlet oxygen. This can be used to make an insoluble deposit that can be stained and then seen by EM. As noted in their abstract, the authors had high hopes for their new method, claiming that: “MiniSOG may do for EM what Green Fluorescent Protein did for fluorescence microscopy”.

miniSOG stains nematode mitochondria for fluorescent (top) and electron (middle) microscopy. The bottom panel shows a miniSOG-stained mouse brain synapse (Shu et al., PLOS Biology).

miniSOG stains nematode mitochondria for fluorescent (top) and electron (middle) microscopy. The bottom panel shows a miniSOG-stained mouse brain synapse (Shu et al., PLOS Biology).

The power of this method from Roger Tsien and colleagues is best exemplified with some images from their paper, just to try and capture your imagination. For an idea of relative size, the scale bar in the top panel shows 50 μm (micrometres), the width of an average human hair. This is a low-resolution fluorescent image of miniSOG that is targeted to the mitochondria of a nematode worm. You could easily have done this with good ol’-fashioned GFP, but the strength of miniSOGs is that you can switch to EM and zoom in much further. The scale bar in the middle panel shows 500 nanometres (nm; 1000 nm = 1μm), so we’ve zoomed in a hundred fold. Now we can see individual mitochondria, and that human hair would be wider than the computer screen you’re using. Yet other images in the paper (like the bottom panel here) use miniSOG to reveal the ultrastructural locations of specific individual labeled cell adhesion molecules – yes, individual proteins – in synapses of an intact mouse brain. As one of our editorial board members, Franck Polleux, puts it this is “a beautiful illustration of the power of combining chemistry, biology and electron microscopy. This new technique dramatically improves the ability of biologists to locate specific proteins inside cells and organelles at nanoscales.”

Xiaokun Shu, first author of the study who now runs a lab at UCSF told me that the success of this project was “a fruit of thinking outside the box.” Shu notes that many people were trying to engineer GFP to be an efficient SOG, but his insights into GFP’s biochemistry led him to conclude it would be a dead-end. And so they hit upon flavin, a cellular chemical that binds to an Arabidopsis protein, phototropin. But the drawback was that unfortunately there was no activation. Shu put his background in studying protein structure and function to good use and engineered this protein to function as an efficient SOG. And the rest, as they say, is history.

Actually, that’s not quite true. Since its publication, this method has already been widely applied to very good use. In another recent PLOS Biology paper from Ben Nichols and colleagues, miniSOG was applied to determine the molecular composition and ultrastructure of the caveolar coat complex. The incredible resolution made possible using the method – and how it compares with super resolution light microscopy – was also discussed in a really nice primer written by Jacomine Krijnse Locker and Sandra L. Schmid.

The landmark EM work of another Nobel laureate, George Palade, can arguably be seen to be the start of cell biology as we know it, but a resurgence in EM may now be underway as our ability to fully harness the technique is brought into a much sharper focus by way of canny biochemical tricks. We can now visualize some of the smallest molecular components of the cell truly at home in their natural habitats, and the combination of live cell light microscopy imaging with such high-resolution EM surely will provide a much clearer picture of cells than we have ever known before.


collection logoSee the Tenth Anniversary PLOS Biology Collection or read the Biologue blog posts highlighting the rest of our selected articles.




ResearchBlogging.orgShu X, Lev-Ram V, Deerinck TJ, Qi Y, Ramko EB, Davidson MW, Jin Y, Ellisman MH, & Tsien RY (2011). A genetically encoded tag for correlated light and electron microscopy of intact cells, tissues, and organisms. PLoS biology, 9 (4) PMID: 21483721

Category: Biology, Cell biology, PLOS Biology, Resources | Tagged | Leave a comment

Scanning for Recent Human Evolution

Modified logo wth textSurvival of the fittest is a concept that is well known to most of us. Heaven knows, many of us strive to remain fit enough to try and extend our life expectancy and survive. But in its original context this relates to natural selection and evolution. A lot of the time natural selection is a conservative force (“negative selection“), trying to keep an organism close to a previously achieved state of perfection. However, occasionally circumstances can change, and selection can then favour genetic changes that will fit an organism better for the new regime. This is what we call “positive selection“, and unlike its rather boring conservative cousin, it can be very interesting indeed.

Continuing the unveiling of our top ten papers selected from the papers published in PLOS Biology over the last decade, the latest choice morsel comes from 2006. The authors developed a new statistical method to search for features that flag those regions of the human genome that may have aided our own adaptation to changing fortunes. They applied this method to the then recently available single nucleotide polymorphism (SNP) data from the International HapMap Project – a catalogue of subtle (but potentially important) genetic variations in different human populations.

By TimVickers at en.wikipedia [Public domain], from Wikimedia Commons The source of this image is the frontispiece of Huxley's 1863 book Man's Place in Nature.

By TimVickers at en.wikipedia [Public domain], from Wikimedia Commons
The source of this image is the frontispiece of Huxley’s 1863 book Man’s Place in Nature.

What do we mean by ‘recent positive selection‘? Well, we’re not talking about how humans evolved from apes, nor are we considering how the last 100 years have changed us, but instead ‘recent’ here means the last ~100,000 years, give or take, during which time modern human populations experienced dramatic environment and lifestyle shifts; Homo sapiens would have left Africa and probably encountered distant cousins H. erectus in Asia and H. neanderthalensis in Europe. They will have needed to adapt to climate and habitat changes as well as to successfully exploit novel food sources and evade newly emerging pathogens. Crucially the authors’ approach specifically looks for genetic variants that are still under ongoing selection, and haven’t yet become universal in the population (haven’t reached “fixation”, in the parlance).

Senior author of the study, Jonathan Pritchard, commented that “this was an important paper for my lab. It really represented the start of our transition into thinking about genome-wide variation data.” He notes also that “[this project] brought me back to thinking about how positive selection shapes the genome… the first area that excited me when I got into biology.” The study was groundbreaking. It presented both the authors’ new statistical method to scan the genome, and many intriguing insights about what had been (and is still being) selected for in humans.

I fully intended to describe the paper to you in some detail, but luckily for me long-time Editorial Board member, and the academic editor who advised us through the review process back then, Laurence Hurst, remembers it well:

“I recall that this paper came at an interesting time.  Plenty of folks were attempting between-species trawls for domains under selection (using Ka/Ks etc) but this was one of the first to consider genome-wide trawls for selection based on SNP/haplotype data and so capture much more recent selection events – potentially events that reflect different selection pressures in different populations.”

He goes on to note that the author came up with “a simple but elegant solution” and that ”all methods of this variety also have problems with demography (which can give false signals), but the paper makes a good crack at doing simulations to try and weed out these issues.”

“I liked this study,” continues Hurst, “not least because it is novel, clever, rigorous and careful, but it is interesting to see what selection is doing.  I find it intriguing, for example, that skin pigment genes appear to be under selection in Europeans. But this isn’t just academic interest: as the authors note, alleles under recent selection are often associated with complex phenotypes of medical relevance. Indeed they identify alleles associated with alcohol susceptibility and salt-sensitive hypertension.”

A map of positive selection along chromosome 2. The blue peak surrounds the lactase gene, already known to be involved in the adaptation to dairy farming. Voight et al., PLOS Biology.

A map of positive selection along chromosome 2. The blue peak surrounds the lactase gene, already known to be involved in the adaptation to dairy farming. Voight et al., PLOS Biology.

In short, the authors  compared SNP data from three populations – Yorubans from sub-Saharan Africa, a combination of Japanese and Chinese individuals from Asia, and a cohort from Europe. They specifically looked across the genome for long blocks of co-inherited DNA (haplotypes) that indicate that a particular SNP (or a nearby feature in the genome) confers some positive advantage on the individual that carries it, and that it is increasing in prevalence in that population. Their new method was a breath of fresh air, and has been widely adopted since then, and they found lots of intriguing biologically and medically relevant results. What’s not to like?

PLOS Biology editorial board member Chris Tyler-Smith noted that this is “A classic paper in my own field, introducing a method that has now become standard”. One of the two co-first authors, Ben Voight, was a graduate student when undertaking this research and is now an Assistant Professor at U. Penn. Voight notes that this paper probably “was a non-trivial factor in getting me where I am today”. In recalling his work on this study, he remembers that given the competitive nature of the field at that time and as a newcomer they were very careful in “crafting the description of the framework, model, and inferences possible. This took a great deal of effort, but in some way was only really possible by a publication framework where we weren’t unnecessarily limited in making that description”.

And it seems that this area is rife for future additional discovery as Pritchard muses “More recently my lab [and others] has argued that adaptation by polygenic selection is likely much more important than standard sweep models… in the next few years it will be possible to make a lot of progress on untangling these issues, helped … by the much richer sequence data that are available today”. Voight told me that “it is clear that this work opened the door to a number of new questions which follow that, even today, have not been flushed out completely: the times these sweeps occurred in human history, the targets, mechanisms, the phenotypes subject to fitness consequences, and the relationship to complex traits and diseases.” And so as our resources and tools improve and advance, our ability to decipher and decode backwards progresses in tandem, leading us to better understand how we came to be who, what, and where we are today. The fascinating research will continue… 

If you want to read more about the original research article, we published both a synopsis and an editorial in the same issue of the journal way back when.


collection logoSee the Tenth Anniversary PLOS Biology Collection or read the Biologue blog posts highlighting the rest of our selected articles.
Voight BF, Kudaravalli S, Wen X, & Pritchard JK (2006). A map of recent positive selection in the human genome. PLoS biology, 4 (3) PMID: 16494531

Category: Biology, Evolution, Genetics, Genomics, PLOS Biology | Tagged | Leave a comment

PLOS Biology – open for cancer research

Cancer, the big C, is not just a single disease; it is a complex beast that, according to data from the National Cancer Institute, will be diagnosed in 1 in 2 people during their lifetime. The Editorial team at PLOS Biology believes strongly that we are Open for a Reason, precisely so that research in areas of high importance reaches the widest audience.  Cancer research is one such area that should be as openly available as possible, with associated data mineable and reusable, ideally in an open access, CC-BY journal as quickly as possible.

Cancer can take hold in numerous locations in the body, can metastasize and travel to other sites, and generally results from cumulative mutations in many genes and pathways. Although the (open access) Annual Report to the Nation on the Status of Cancer [1] reports an encouraging overall decline in cancer death rates, many of us will have lost someone, or know someone currently battling with cancer, and it continues to devastate lives.

Despite research and advanced treatment options leading to an increased survival rate for many kinds of cancer, there is still a lot that we don’t understand. Cancer research does not encapsulate just one small area of research, instead it encompasses investigations across a broad range of mechanisms in many genes and pathways using a range of model organisms, not least, humans. Many questions remain as to what triggers the onset of cancer, tumour progression and metastasis; how we can best identify new targets for drug development; and of course how best to treat the disease in its many forms.

Given the worldwide impact of cancer from a financial and economic perspective, as well as from a more emotive one, publishing cancer research in an open access forum is one way to ensure that those who need access to  AACR2_300x250research discoveries from across this broad field have that access as quickly and as easily as possible. PLOS Biology is open for just this reason, and we publish many high impact publications that relate to cancer one way or another. For this reason, we encourage cancer researchers to consider PLOS Biology as a high visibility venue for your future research. We are interested in all areas of cancer research traversing the bedside-to-bench spectrum, and we welcome translational studies.

Later this week, I will be representing PLOS Biology at the American Association of Cancer Research (AACR) Annual Meeting 2013, along with colleagues from PLOS Medicine and PLOS ONE.  Last year at the AACR meeting, there were nearly 17,000 attendees from 70 countries; based in Washington DC this year, no doubt thousands will again gather to discuss the latest, most interesting findings in all areas of cancer research.

If you’re attending and want to find out more about how to publish in an Open Access journal, you can visit the PLOS booth to learn more about PLOS Biology, meet me and others from PLOS at our booth, number 544. We’re planning a meet the editor session from 12 til 1:30 pm on Monday 8th April; stop by to leave a message for me, or email me at biologue[at], and we can arrange a time to chat.

We’ve gathered some examples of research articles in various aspects of cancer biology that have been published in PLOS Biology over the last few years, so if you’re interested in seeing some of the great research we publish, take a look at our AACR Collection 2013.


[1] ‘Annual Report to the Nation on the Status of Cancer, 1975–2009, Featuring the Burden and Trends in Human Papillomavirus (HPV)–Associated Cancers and HPV Vaccination Coverage Levels’
Ahmedin Jemal, Edgar P. Simard, Christina Dorell, Anne-Michelle Noone, Lauri E. Markowitz, Betsy Kohler, Christie Eheman, Mona Saraiya, Priti Bandi, Debbie Saslow, Kathleen A. Cronin, Meg Watson, Mark Schiffman, S. Jane Henley, Maria J. Schymura, Robert N. Anderson, David Yankey, and Brenda K. Edwards
JNCI J Natl Cancer Inst (2013) 105(3): 175-201 first published online January 7, 2013 doi:10.1093/jnci/djs491



Category: Biology, Cancer, Conference, Disease, Open access, PLOS Biology | Tagged , , , | 4 Comments

AACR Collection 2013


Mejia R (2010) Cancer Courts Immune Response to Aid Growth. PLoS Biol 8(12): e1001004. doi:10.1371/journal.pbio.1001004

The Editorial team at PLOS Biology believes strongly that we are Open for a Reason; precisely so that research in areas of high importance reaches the widest audience.  Cancer research is one such area that should be as openly available, with associated data mineable and reusable, ideally in an open access, CC-BY journal as quickly as possible. Open access ensures the most expedient, economic and practical route to discovery and to developing potential therapeutic advances for the suite of diseases and conditions that we tend to over-simplify and apply one name to, cancer.

PLOS Biology is open for cancer research, and to highlight some of the discoveries we’ve published in this broad field, we’ve gathered together some research articles that cover various aspects of cancer biology published in PLOS Biology over the last few years, so if you’re interested in learning more about some of this great research take a look:

Nonheritable Cellular Variability Accelerates the Evolutionary Processes of Cancer.
Frank SA, Rosner MR (2012)
PLOS Biol 10(4): e1001296. doi:10.1371/journal.pbio.1001296

Book review:
Cancer: The Whole Story.
Frank SA (2011)
PLOS Biol 9(4): e1001044. doi:10.1371/journal.pbio.1001044

Cancer Courts Immune Response to Aid Growth.
Mejia R (2010)
PLOS Biol 8(12): e1001004. doi:10.1371/journal.pbio.1001004

And Corresponding Research Article:
Live Imaging of Innate Immune Cell Sensing of Transformed Cells in Zebrafish Larvae: Parallels between Tumor Initiation and Wound Inflammation.
Feng Y, Santoriello C, Mione M, Hurlstone A, Martin P (2010)
PLOS Biol 8(12): e1000562. doi:10.1371/journal.pbio.1000562

Research Articles:

ELF5 Suppresses Estrogen Sensitivity and Underpins the Acquisition of Antiestrogen Resistance in Luminal Breast Cancer.
Kalyuga M, Gallego-Ortega D, Lee HJ, Roden DL, Cowley MJ, et al. (2012)
PLOS Biol 10(12): e1001461. doi:10.1371/journal.pbio.1001461

Stimulation of Host Bone Marrow Stromal Cells by Sympathetic Nerves Promotes Breast Cancer Bone Metastasis in Mice.
Citation: Campbell JP, Karolak MR, Ma Y, Perrien DS, Masood-Campbell SK, et al. (2012) PLOS Biol 10(7): e1001363. doi:10.1371/journal.pbio.1001363

Novel Role of NOX in Supporting Aerobic Glycolysis in Cancer Cells with Mitochondrial Dysfunction and as a Potential Target for Cancer Therapy.
Lu W, Hu Y, Chen G, Chen Z, Zhang H, et al. (2012)
PLOS Biol 10(5): e1001326. doi:10.1371/journal.pbio.1001326

ESRRA-C11orf20 Is a Recurrent Gene Fusion in Serous Ovarian Carcinoma.
Citation: Salzman J, Marinelli RJ, Wang PL, Green AE, Nielsen JS, et al. (2011)
PLOS Biol 9(9): e1001156. doi:10.1371/journal.pbio.1001156

Mesenchymal Transition and Dissemination of Cancer Cells Is Driven by Myeloid-Derived Suppressor Cells Infiltrating the Primary Tumor.
Toh B, Wang X, Keeble J, Sim WJ, Khoo K, et al. (2011)
PLOS Biol 9(9): e1001162. doi:10.1371/journal.pbio.1001162

HER2 Phosphorylation Is Maintained by a PKB Negative Feedback Loop in Response to Anti-HER2 Herceptin in Breast Cancer.
Gijsen M, King P, Perera T, Parker PJ, Harris AL, et al. (2010)
PLOS Biol 8(12): e1000563. doi:10.1371/journal.pbio.1000563

Targeting A20 Decreases Glioma Stem Cell Survival and Tumor Growth.
Hjelmeland AB, Wu Q, Wickman S, Eyler C, Heddleston J, et al. (2010)
PLOS Biol 8(2): e1000319. doi:10.1371/journal.pbio.1000319

If you visit the PLOS booth (booth #544) at the AACR Annual Meeting 2013, you can collect a printed version of this collection. We hope that you will enjoy these research and magazine articles from PLOS Biology; as with all of our content they are Open Access and freely available to all.

We encourage you to consider PLOS Biology as a high visibility venue for your future research. We are interested in all areas of cancer research traversing the bedside-to-bench spectrum, and we welcome translational studies. Our editorial model involves a partnership between professional and academic editors that guarantees our authors the best of both worlds; editorial expertise from the in-house team combined with the up-to-date specialised scientific knowledge of your colleagues who serve on our editorial board.

We hope you find this collection interesting. For more information about PLOS Biology and to submit your research, please visit




Category: Biology, Cancer, Conference, Disease, Open access, PLOS Biology | Tagged , , , | Leave a comment