28 Jan 2013

Dung beetles follow the Milky Way

After the sun sets over the African savannah, the nocturnal male beetle Scarabaeus satyrus leaves its nest in the ground to go on a hunt for a pile of fresh dung. Once he finds the fuming manure, the beetle franticly sculpts it into a ball and rolls it away as quickly as possible to escape competition from vicious dung stealers. At a safe distance from the dung heap, the beetle buries the ball and, if he is lucky, a female will mate with him and then lay her eggs inside the secluded excrement. Otherwise, he simply enjoys feeding on its nutritious content.

Beetle making dung ball (Credit: Marcus Byrne)

The fastest way to get away from the perilous dung pile is to move in a straight line. This is an easy task for the beetle’s diurnal cousins, which can use the sun and terrestrial landmarks, like trees, to guide their way, but for nocturnal dung beetles staying on their path can be quite tricky. New research in Current Biology now shows that dung beetles can use the Milky Way as a compass. “This is the first animal known that does this” says Eric Warrant, leading author in the study.

Even in a full moon, the sunlight reflected by the moon is a million times weaker than direct sunlight. Despite this, beetles and other nocturnal insects such as ants and moths know their way around astonishingly well, as well as diurnal insects in fact. The secret lies in their super-sensitive compound eyes, which are extremely well adapted to see in dim light. For beetles, as for most insects, the main night guidance cue is undoubtedly the moon.

But what happens in moonless nights? A few years ago, while studying how beetles use the polarised moonlight pattern as compass, Warrant and colleagues at the University of Lund noticed that, even in moonless nights, the beetles could still roll their dung balls in a straight line. The only possible remaining visual cue was the stars. “We found this quite a surprise and set out to test whether the beetles were using the stars to orientate” says Warrant “It turned out they did, which was really remarkable!”

Beetle with eye cap (Credit: Marcus Byrne)

The scientists travelled to South Africa to do field experiments under S. satyrus’s native southern-hemisphere starry sky. They placed the beetles with their dung balls in the centre of a circle enclosed by a black cloth (to hide any terrestrial landmark), and measured how long they took to reach the edge of the circle. Under a full moon, the beetles rolled their dung balls in a straight line and quickly reached the periphery. However, on a cloudy night, or when their eyes were covered by tiny cardboard caps, the beetles took six times longer to reach the edge of the circle- they were lost. What happened in moonless, but starry nights? When the only celestial cue available was the stars, the beetles swiftly rolled their balls in a straight direction.

The beetles’ tiny compound eyes, however, are in theory not sensitive enough to distinguish individual stars, but they might detect the Milky Way or constellations, the scientists thought. They tested this in a planetarium, where they could switch stars on and off and check how the beetles behaved under different starry skies. “We found that nocturnal ball-rolling dung beetles are able to roll dung balls in straight lines […] by using the Milky Way as a compass cue” says Warrant. The authors showed that, rather than using the stars themselves, the beetles use the bright streak of light formed by the Milky Way as guidance cue.

Field experiments (Credit: Marcus Byrne)

Jochen Zeil, an expert in insect navigation from the Australian National University says “The demonstration that an insect with compound eyes that have very low resolution […] can perceive structure in the night sky is significant and interesting.”

Nocturnal insects have morphological adaptations that increase the sensitivity of their eyes. For instance, nocturnal dung beetles have huge light-sensitive cells in their retinas capable of detecting many more photons than the retinas of their diurnal counterparts.

“The main and fascinating remaining question in the context of the present study will be whether the beetles can perceive individual stars” says RĂ¼diger Wehner, a neurophysiologist specialised in insect vision from the University of Zurich. Warrant suspects they can: “It is very likely that the beetles can see the brightest stars in the sky […] but exactly how many remains to be determined, but this is something we plan to do.”

Dacke, M., Baird, E., Byrne, M., Scholtz, C., & Warrant, E. (2013). Dung Beetles Use the Milky Way for Orientation Current Biology DOI: 10.1016/j.cub.2012.12.034

This article was published in Lab Times on 28-01-13. You can read it here.

21 Jan 2013

Cancer research: fruit flies take it down a notch

You wouldn’t think that those pesky flies hovering around your fruit bowl could help scientists understand cancer. Flies don’t have cancer, and a fly is, well, just a fly. However, the fruit fly Drosophila melanogaster has been one of scientists' favourite animal models for over a century, and is nowadays used to study many human diseases. New research using fruit flies has now uncovered molecular details in tissue overgrowth that explain some long-standing questions in cancer research.

Why Drosophila? When compared to other lab animals like mice, for instance, flies have many advantages. They are tiny and hence you can grow them anywhere, they are cheap to maintain (in the old days they were fed with rotten bananas) and they breed in just 12 days while mice take 12 weeks. But the most important fact is that, even though flies and humans look very different, most of their genes are the same, or very similar. So while manipulating fly genes in the lab is quite easy, when scientists understand how a gene works in the fly, these discoveries can have significant implications for human medicine.

Fruit fly Drosophila melanogaster (Credit: therealbeast/everystockphoto)

To study a human disease in flies scientists begin by making them sick. They mutate, or disrupt, the same gene that is known (or suspected) to cause the human disease, and then they try to figure out why meddling with this particular gene causes the disease symptoms, which in flies are called phenotypes. And this is exactly what Sarah Bray’s team at the University of Cambridge did to understand the molecular details of tissue overgrowth that may lead to cancer.

In a study published in the January issue of EMBO Journal, the Cambridge scientists introduced in flies a modified version of the Notch gene that makes it overactive, or in other words, the gene is always turned on, and this set off massive tissue overgrowth in the larvae, mimicking what happens in cancer. Notch is a gene that is overactive in many cancers such as breast, lung and cervical cancers, but how Notch activation triggers cancer is not understood.

The Notch gene encodes for a protein involved in cell communication. When Notch receives a signal from a neighbouring cell, it becomes activated and instructs specific genes to switch on. Each of these genes does a different job in the cell, such as telling the cell to multiply. The problem is that, with the same signal, Notch can activate many genes, and it is difficult for scientists to predict what the combined effect of turning on all these genes will be for a cell or a tissue. To make matters worse, Notch activation can have opposite cellular outcomes. For instance, in some cases Notch causes tissue overgrowth and cancer, while in others Notch stops tissue growth. This paradox has been puzzling scientists for over a decade, and is a major factor hindering progress in Notch cancer research.

Magnified Drosophila larval tissue with fluorescent marker. Left: normal tissue, right: tissue with overactive Notch. (Credit: Bray lab, University of Cambridge)

To try and solve this problem, Bray's team used genomic approaches to search for genes activated by Notch in the overgrown tumour-like larval tissues. The researchers figured that knowing which genes are abnormally activated by Notch in their simplified ‘cancer’ fly model might explain the different cellular responses to Notch. And this is exactly what they found. “We found that in a same tissue, Notch activates genes that seem antagonistic” says Alexandre Djiane, leading author in the study. But when they had a closer look the team found that these opposing genes “are actually activated in different subsets of the tissue.” Notch activation produced a central region in the tissue where cells divided slowly, surrounded by cells that multiplied very quickly. How does Notch induce these different cellular responses? Djiane explains “this regionalisation of the response is at least in part a consequence of cross-regulation between the different Notch targets themselves”. Notch can not only activate different genes in the same tissue, but some genes can also interfere with one another, in a sort of battle between genes where the winner gets to tell the cell what to do.

But are these newly found genes involved in cancer? By comparing their results with cancer patients’ databases, the authors found that several of the genes abnormally activated by Notch in the fly overgrown tissue were overactive in human cancers. This is a good indication that the genes identified in the fly may be potential candidate cancer-promoting genes in humans. But the researchers went even further. They used genetic tricks that turned these genes up or down to test what they actually do in living flies, and found that about two thirds “play a role in tissue growth and mediate the effect of Notch,” says Djiane.

“The advantage of the fruit fly is, as demonstrated in this work, that several of these candidates can be rigorously tested via fast and efficient genetic testing to confirm the functional importance of each target gene” says Marcos Vidal, a cancer biologist at the Beatson Institute for Cancer Research in Glasgow who was not involved in this study. “This kind of research complements the one performed directly from clinical samples and cell lines.”

Current cancer drugs targeting Notch have side effects because Notch is critical for many biological processes. Vidal says “[…] direct inhibition of Notch appears to have undesired side effects and therefore may not be an ideal therapeutic target itself. On the other hand, the gene targets specifically regulated by Notch in tumorous growth identified in this study, could potentially be better therapeutic targets in Notch-driven cancers.”

Djiane, A., Krejci, A., Bernard, F., Fexova, S., Millen, K., & Bray, S. (2013). Dissecting the mechanisms of Notch induced hyperplasia The EMBO Journal, 32 (1), 60-71 DOI: 10.1038/emboj.2012.326

This article was published in The Munich Eye on the 21-01-13. You can read it here.