Pain-Sensing Gene Named for Rocky

Guest Post By Sheena Faherty, graduate student in Biology

How do our neurons discriminate between a punch to the face or a kiss on the cheek? Between something potentially harmful, and something pleasant?

A new study published this week in Current Biology offers an answer by describing a previously uncharacterized gene required for pain sensing.

This work comes out of Dan Tracey’s lab at the Duke Institute for Brain Sciences. They named the gene balboa in honor of fictional prizefighter Rocky Balboa and his iconic immunity to pain.

Stallone as Rocky

Float like a drosophila, sting like a …oh, never mind.

The researchers found that the balboa gene is only active in pain-sensing neurons and is required for detection of painful touch responses. Without it, neurons can’t distinguish between something harmful and something pleasant.

Does the ultimate prize of naming of the gene inspire any boxing matches between lab mates?

“In the fly community, we are allowed to have these creative gene names, so discussions about the decision on naming are more fun than argumentative,” Tracey says.

Tracey’s lab is concerned with sensory neurobiology, the study of how neurons transform cues from the surrounding environment to signals that can be interpreted by the brain. Ultimately, the lab group hopes to identify the underlying molecular mechanisms that are involved in our sense of touch.

Pugilistic fly artwork designed by Jason Wu, a neurobiology graduate student in Jorg Grandl's lab

Pugilistic fly artwork designed by Jason Wu, a neurobiology graduate student in Jorg Grandl’s lab

“It’s unclear what happens during that moment of touch sensation when sensory neurons detect and convert a touch stimulus into a nerve impulse,” said graduate student Stephanie Mauthner, who is the lead author on the Rocky paper. “It’s also ambiguous how nerves are capable of discriminating the threshold of touch intensity.”

Although the fruit fly has a relatively simple central nervous system, Tracey’s group uses it as model because it has many of the same neural circuits that the human brain has.

“[Our goal was to figure out] what molecular components are required for pain neurons to detect harsh touch responses and what is the mechanism for performing this task,” Mauthner said.

Using fluorescent cells, their study also shows that balboa interacts with another protein of the same family named pickpocket. They’re hopeful that this gene duo can be a potential target for pain medications that could discriminate between different sites of pain throughout the body.

Pain relievers such as aspirin or ibuprofen work broadly throughout the whole body—with no discrimination to where the pain is actually occurring. But, by working towards the exact molecular mechanism of pain signaling, genes like balboa and pickpocket are potential candidates for more targeted therapeutics.

Grad student Stephanie Mauthner, hangs out with one of her many vials of flies (courtesy of Stephanie Mauthner)

Grad student Stephanie Mauthner hangs out with one of her many vials of flies (courtesy of Stephanie Mauthner)

CITATION: “Balboa Binds to Pickpocket In Vivo and Is Required for Mechanical Nociception in Drosophila Larvae,” Stephanie E. Mauthner, Richard Y. Hwang, Amanda H. Lewis, Qi Xiao, Asako Tsubouchi, Yu Wang, Ken Honjo, J.H. Pate Skene, Jörg Grandl, W. Daniel Tracey Jr. Current Biology, Dec. 15, 2014. DOI: http://dx.doi.org/10.1016/j.cub.2014.10.038

Pursuit Of Bird Brains Takes Researchers Back 66 Million Years

A handful of bird species survived the K-T extinction. Chicken genomes have changed the least since that terrible day.

A handful of bird species survived the K-T extinction. Chicken genomes have changed the least since that terrible day.

By Karl Leif Bates

In the beginning was the Chicken. Or something quite like it.

At that moment 66 million years ago when an asteroid impact caused the devastating Cretaceous–Tertiary (K-T) extinction, a handful of bird-like dinosaur species somehow managed to survive.

The cataclysm and its ensuing climate change wiped out much of Earth’s life and brought the dinosaurs’ 160-million-year reign to an end.

But this week, the genomes of modern birds are telling us that a few resourceful survivors somehow scratched out a living, reproduced (of course), and put forth heirs that evolved to adapt into all the ecological niches left vacant by the mass extinction. From that close call, birds blossomed into the more than 10,000 spectacularly diverse species we know today.

Erich Jarvis

Erich Jarvis

Not all birds are descended from chickens, but it’s true that chicken genes have diverged the least from the dinosaur ancestors, says Erich Jarvis, an associate professor of neurobiology in the Duke Medical School and Howard Hughes Medical Institute Investigator.

He’s one of the leaders on a gigantic release of scientific data and papers that tells the story of the plucky K-T survivors and their descendants, redrawing many parts of the bird family tree.

From giant, flightless ostriches to tiny, miraculous hummingbirds, the descendants of those proto-birds now rule over the skies, the forests, the cliff-faces and prairies and even under water. While other birds were learning to reproduce songs and sounds, hover to drink nectar, dive on prey at 230 miles per hour, run across the land at 40 miles per hour, migrate from pole to pole or spend months at sea out of sight of land, the chickens just abided, apparently.

terror birds

Sweet little chickadees had a very big, very scary cousin. “Parrots and songbirds and hawks and eagles had a common ancestor that was an apex predator,” Erich Jarvis says. “We think it was related to these giant ‘terror birds’ that lived in the South American continent millions of years ago.”

The new analyses released this week are based on complete-genome sequencing done mostly at BGI (formerly Beijing Genomics Institute). and DNA samples prepared mostly at Duke. The budgerigar, a parrot, was sequenced at Duke. There are 29 papers in this first release, but many more will tumble out for years to come.

“In the past, people have been using 1, 2, up to 20 genes, to try to infer species relationships over the last 100 million years or so,” Jarvis says. But whole-genome analysis drew a somewhat different tree and yielded important new insights.

More than 200 researchers at 80 institutions dove into this sea of big data like so many cormorants and pelicans, coming up with new insights about how flight developed and was lost several times, how penguins learned to be cold and wet and fly underwater and how color vision and bright plumage co-evolved.

The birds’ genomes were found to be pared down to eliminate repetitive sequences of DNA, but yet to still hold microchromosomal structures that link them to the dinosaurs and crocodiles.

The sequencing of still more birds continues apace as the Jarvis lab at Duke does most of the sample preparation to turn specimens of bird flesh into purified DNA for whole-genome sequencing at BGI. (More after the movie!)

As one of three ring-leaders for this massive effort, Erich Jarvis is on 20 papers in this first set of findings. Eight of those concern the development of song learning and speech, but the other ones are pretty cool too:

Evidence for a single loss of mineralized teeth in the common avian ancestor. Robert W. Meredith, et al. Science. Instead of teeth, modern birds have a horny beak to grab and a muscular gizzard to “chew” their food. This analysis shows birds lost the use of five genes related to making enamel and dentin just once about 116 million years ago.

Complex evolutionary trajectories of sex chromosomes across bird taxa. Qi Zhou, et al. Science. The chromosomes that determine sex in birds, the W and the Z, have a very complex history and more active genes than had been expected. They may hold the secret to why some birds have wildly different male and female forms.

Three crocodilians genomes reveal ancestral patterns of evolution among archosaurs. Richard E Green, et al Science. Three members of the crocodile lineage were sequenced revealing ‘an exceptionally slow rate of genome evolution’ and a reconstruction of a partial genome of the common ancestor to all crocs, birds, and dinosaurs.

Evidence for GC-biased gene conversion as a driver of between-lineage differences in avian base composition. Claudia C. Weber, et al, Genome Biology. The substitution of the DNA basepairs G and C was found to be higher in the genomes of birds with large populations and shorter generations, confirming a theoretical prediction that GC content is affected by life history of a species.

Low frequency of paleoviral infiltration across the avian phylogeny. Jie Cui, et al. Genome Biology. Genomes maintain a partial record of the viruses an organism’s family has encountered through history. The researchers found that birds don’t hold as much of these leftover bits of viral genes as other animals. They conclude birds are either less susceptible to viral infection, or better at purging viral genes.

Genomic signatures of near-extinction and rebirth of the Crested Ibis and other endangered bird species. Shengbin Li, et al Genome Biology. Genomes of several bird species that are recovering from near-extinction show clues to the susceptibilities to climate change, agrochemicals and overhunting that put them in peril. This effort has created better information for improving conservation and breeding these species back to health.

Dynamic evolution of the alpha (α) and beta (β) keratins has accompanied integument diversification and the adaptation of birds into novel lifestyles. Matthew J. Greenwold, et al. BMC Evolutionary Biology.  Keratin, the structural protein that makes hair, fingernails and skin in mammals, also makes feathers. Beta-keratin genes have undergone widespread evolution to account for the many forms of feathers and claws among birds.

Comparative genomics reveals molecular features unique to the songbird lineage. Morgan Wirthlin, et al. BMC Genomics. Analysis of 48 complete bird genomes and 4 non-bird genomes identified 10 genes unique to the songbirds, which account for almost half of bird species today. Two of the genes are more active in the vocal learning centers of the songbird brain.

Reconstruction of gross avian genome structure, organization and evolution suggests that the chicken lineage most closely resembles the dinosaur avian ancestor. Michael N. Romanov, et al. BMC Biology. Of 21 bird species analyzed, the chicken lineage appears to have undergone the fewest changes compared to the dinosaur ancestor.

Two Antarctic penguin genomes reveal insights into their evolutionary history and molecular changes related to the cold aquatic environment. Cai Li, et al. Gigascience. The first penguins appeared 60 million years ago during a period of global warming. Comparisons of two Antarctic species show differences and commonalities in gene adaptations for extreme cold and underwater swimming.

Evolutionary genomics and adaptive evolution of the hedgehog gene family (SHH, IHH, and DHH) in vertebrates. Joana Pereira, et al. PLoS ONE. Whole-genome sequences for 45 bird species and 3 non-bird species allow a more detailed tracing of the evolutionary history of three genes important to embryo development.

A Duke lab led the effort to isolate bird DNA for sequencing at BGI: (L-R) Erich Jarvis, associate professor of neurobiology and Howard Hughes Medical Institute investigator, lab research analyst Carole Parent, undergraduate research assistant Nisarg Dabhi, and research scientist Jason Howard. (Duke Photo, Les Todd)

A Duke lab led the effort to isolate bird DNA for sequencing at BGI: (L-R) Erich Jarvis, associate professor of neurobiology and Howard Hughes Medical Institute investigator, lab research analyst Carole Parent, undergraduate research assistant Nisarg Dabhi, and research scientist Jason Howard. (Duke Photo, Les Todd)

Kumbaya and All That… Until Thursday!

By Karl Leif Bates

You wouldn’t know it from the war drums banging over at ESPN this week in advance of Thursday night’s football showdown, or the hairy eyeball the frat boys give you for wearing the wrong shirt in Chapel Hill, but our two fine institutions, Duke and UNC-Chapel Hill, are actually very good friends and close collaborators. …At the faculty level, at least.

A February 2013 map showing which blue Facebook users follow during March Madness. (We're huge in NW Arizona, okay?)

A February 2013 map showing which blue Facebook users follow during March Madness. (We’re huge in NW Arizona, okay?)

It’s quite common for a major research paper coming out of either campus to include collaborators from the other Tier 1 research university just 10 miles away. It only makes sense. When the ARRA Stimulus funding was on the table a few years ago, the two pulled together on all sorts of projects to bring about $400 million in federal tax dollars back to the Triangle.

And now, a new program announced just a few weeks ago will actually pay researchers from both schools to be friends! Can you imagine?

A Chapel Hill taunt. (Not actually supported by the data, but whatever.)

A Chapel Hill taunt. (Not actually supported by the data, but whatever.)

Duke’s Translational Medicine Institute (DTMI) and the North Carolina Translational and Clinical Sciences Institute (NC TraCS) are awarding $50,000 grants to research projects that are trying to speed laboratory medical findings into the clinic or the population. (That’s what “translation” means.) The only catch is that the application has to include one co-investigator from each school.

“I think that although we come from different ends of Tobacco Road and our different shades of blue compete passionately in sports, when it comes to translating medical progress and health care to the community, we can be very collaborative,” Jennifer Li of the Duke Translational Medicine Institute told the DTMI newsletter.

Just look at those long faces! Poor kids. A Duke buzzer-beater will do that to you.

Just look at those long faces! Poor kids. A Duke buzzer-beater will do that to you.

Naturally, the newsletter then had to quote a Tarheel: “On a scientific basis, collaborative teams are formed based on shared interests and complimentary resources, skills and experiences,” said John Buse, deputy director of the NC Translational and Clinical Sciences Institute. “The hope (is) that the sum is greater than the parts.”

Perhaps, Dr. Buse, perhaps. But what’s the fun in that?

GO DUKE !

World Domination in a Loaf of Bread

By Robin Smith

If baker’s yeast could take over the world, the bread leavener’s world domination might look like this time-lapse movie produced by a team led by Duke biologist Nicolas Buchler:

Their report in the Nov. 5, 2014, issue of the journal Molecular Biology of the Cell shows time-lapse images of yeast cells under a microscope as one cell grows and divides into two, and two into four, and so on.

To watch the budding yeasts in action, the researchers inserted a gene for an enzyme that gives fireflies their characteristic yellow light into the yeasts’ DNA.

It normally takes one yeast cell about 90 minutes to grow and divide into two new cells. But in the time-lapse movie, the process is compressed into a few seconds.

The yellow dots show genes being turned on and off in the nucleus of each cell.

The approach allows scientists to track the activation and deactivation of genes over a tiny cell’s fast life cycle more accurately than standard labeling techniques using other glowing proteins, the researchers say.

CITATION: “Measuring fast gene dynamics in single cells with timelapse luminescence microscopy,” Mazo-Vargas, A., Park, H., Aydin, M. and N. Buchler. Molecular Biology of the Cell, November 5, 2014.

All Ears for Corn Genetics

By Nonie Arora

“Technology is progress” and “new is better” seem to be mantras in some fields of research. However, when it comes to fields of genetically modified corn, we might be wise to think otherwise.

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Dr. Mary Eubanks and Students at the Campus Farm. Credit: Nonie Arora

Duke biology professor Dr. Mary Eubanks spoke to a group of Duke students, community members, and a farmer from Togo about corn genetics in a workshop held Friday, Oct. 24 at the Duke Campus Farm. Dr. Eubanks founded her own seed genetics company (Sun Dance Genetics LLC) and is a leading advocate for changing the way we grow corn.

Dr. Eubanks became intrigued by the origins of corn while studying the origins of agriculture and the start of American civilization in an archaeology PhD program. She realized that she wouldn’t be able to answer her questions about what she considered to be this “great botanical mystery” without an understanding of genetics. To uncover this mystery, she pursued a postdoctoral program in corn genetics. Based on her experimentation, she developed the hypothesis that maize domestication involved something called intergeneric hybridization, or crossing between plants in different genera.

European Corn Borner attacks Maize. Credit: Wikimedia commons

European Corn Borner attacks Maize. Credit: Wikimedia commons

During her career, Dr. Eubanks also worked in regulatory affairs and learned about the devastating effects of chemical pesticides. She became an advocate for sustainable agriculture: finding ways to develop pest-resistant corn without genetic engineering. She has successfully transferred natural resistance to the worst insect pests of corn — corn rootworm and European corn borer.

In contrast to using natural breeding methods to create new lines of corn, genetically modifying organisms could have negative effects on human health, according to Dr. Eubanks. Dr. Eubanks believes that the inserter and promoter sequences that are used to get the genes to express the foreign proteins can lead to antibiotic resistance and intestinal issues for humans.

The group was surprised by her description of her own anaphylactic shock reaction to Bt-corn, a GMO. Her own personal history of the allergic reaction made her think of the potential reactions our bodies could be having to GMOs. Dr. Eubanks described how it was problematic that genes being introduced to the crop came from other organisms and that humans haven’t evolved a tolerance to the proteins the genes encode. This could lead to potential allergenicity in humans. According to Dr. Eubanks, it is possible that there has been horizontal gene transfer between plasmids — small molecules used to insert genes from one organism to the next — and the human gut.

When asked about the regulations regarding GMOs, Dr. Eubanks explained that the FDA is in charge of the labeling and GMOs are generally regarded as safe so long as they are substantially equivalent to the other food product. The industry is very opposed to the labeling of GMOs and 90% of the corn, cotton, and soy available has some GMO product in it, according to Dr. Eubanks. She believes that not enough is being done to regulate the industry.

We were intrigued by her discussion of food security and funding for interventions. She described that a lot of international work on food security highly promotes technology and the big industry agricultural model. Dr. Eubanks believes we need to change our paradigm from thinking that the most advanced technological options are always best to considering an ecological intensification approach. Such an approach seeks to design more productive, sustainable production systems that are well suited to their environments by better understanding how nature functions. Her current work is helping bring food security to South Sudan through corn that is pest-resistant and drought-tolerant.

 

Scents Are Key to Lemur Nightlife

LEMUR SUPERPOWER #457:  Some lemurs can safely digest cyanide in amounts sufficient to kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. To add to their list of superpowers, lemurs also have especially keen powers of scent.

Buried in the nose of Fuggles the mouse lemur are specialized pheromone receptors that help her distinguish friend from foe in the dark of night, when mouse lemurs are active.

By Robin Ann Smith

If you could pick one superpower, consider taking inspiration from lemurs. Some lemurs can safely digest cyanide in amounts that would kill an elephant. Others can enter hibernation-like states to survive periods when food and water are in short supply. Still others have keen powers of scent, with the ability to find mates and avoid enemies in the darkness by smell alone.

Research by biologist and Duke Lemur Center director Anne Yoder suggests that the molecular machinery for sniffing out pheromones — much of which has gone defunct in humans and many other primates — is still alive and well in lemurs and lorises, our distant primate cousins.

Lemurs use scents to mark the boundaries of their territories, distinguish males from females and figure out whether another animal is friend or foe. When a lemur gets a whiff of another animal, specialized pheromone receptors in the lining of the nose transmit the information to the brain, triggering instinctive urges like mating, defense and avoiding predators.

The receptors are proteins encoded by a family of genes called V1Rs. First identified in rats in the mid-1990s, V1R genes are found in animals ranging from lampreys to humans. But the proportion of these pheromone-detection genes that actually functions varies greatly from one species to the next, Yoder said last week in a roundtable discussion hosted by Duke’s Science & Society program.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Randy the ring-tailed lemur scent-marks his territory. Photo by David Haring.

Studies suggest that as much as 90% to 100% of the pheromone-detection genes in humans consist of disabled pieces of DNA, called pseudogenes.

“Our pheromone-detection genes are so boring — we don’t have many of them, and almost all of them are broken,” Yoder said.

But in lemurs and lorises — whose ancestors split off from the rest of the primate family tree more than 60 million years ago — the proportion of pheromone-detection genes that is still intact is much higher.

In a study published this year, Yoder and colleagues analyzed the DNA of 19 species and subspecies of lemurs and lorises, looking for subtle differences in their V1R genes. They found that one group — the mouse lemurs — has the highest proportion of intact V1R sequences of any mammal yet studied.

To find out which genes are linked to which scents, Yoder and her colleagues plan to take DNA sequences from pheromone-detecting genes in lemurs, insert them into mice, and expose the mice to different scents to see how they respond.

An ability to sniff out the right mates — and avoid being seduced by the wrong suitors — may have served as a mating barrier that allowed lemur species to diverge after arriving in their island home of Madagascar, helping to explain how the more than 70 living species of lemurs came to be, Yoder says.