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.

Duke Undergraduate Research Society. Hit them up.

By Lyndsey Garcia

I have a confession: I have never personally been interested in performing research. I love to read, listen, and talk about research and latest developments, but never saw myself micropipetting or crunching raw data in the lab. But after attending the Duke Undergraduate Research Society (DURS) Kickoff, they got me to sign up for their listserve!

DURS Executive Board: (from left to right) Joseph Kleinhenz, Syed Adil, Lillian Kang, Dr. Huntington Willard, Sammie Truong, John Bentley

DURS Executive Board: (from left to right) Joseph Kleinhenz, Syed Adil, Lillian Kang, Dr. Huntington Willard, Sammie Truong, John Bentley

The kickoff highlighted DURS’s leading man, Dr. Huntington Willard. He was a biology pre-med undergraduate at Harvard for 3 years until he was introduced to genome research, which quickly became his life’s passion.

In 2002, Willard launched the Institute for Genome Sciences and Policy at Duke, which grew to more than 100 faculty and 300 staff members. The institute unfortunately met its end this past June, but Willard continues his love and passion for genome research here at Duke, and with Duke undergraduate students.

Before creating IGSP, Willard had only interacted with medical and graduate students during his research. But at Duke he had his first opportunity to engage with  undergrads.

“The best thing at Duke is the undergrads and I wanted to take advantage of the best thing at Duke,” he says.

Willard explains his love for research by explaining the inherent differences between all Duke students and those Duke students who perform research. All Duke students love to learn and are interested in what they are learning, but Duke students who research are questioners. He says they want to know more than what is given in the textbook. They constantly go between B and C on the test because there could be valid reasons for both, but we just don’t know why yet. They aren’t afraid to delve into uncharted territories where there is no safety net of certainty.

Willard says many of these young researchers seem to follow his own motto: “This is so cool. I want to know how it works.”

Willard’s talk already had me inspired, but then I got to hear from the executive board of DURS. Each member explained the research they are involved with on campus and how they got there. They explained how they sent tons of emails to professors and received no responses and gave anecdotes about switching labs because it wasn’t what they wanted.

They also expanded on what DURS offers to undergraduates. The program connects professors and undergraduates for potential research positions, sets up workshops to help make networking contacts, pairs young undergrads with experienced undergrads to mentor and give advice, and helps one realize that no one came out of the womb with lab experience, so don’t be discouraged by not having any at first.

“This is exactly why I came to Duke. It’s a great university with amazing research opportunities and now I can’t wait to get started.” – Freshman Jaclyn Onufrey.

So my takeaway from Duke Undergraduate Research Society was:

1)      Are you interested in questioning the unknown?

2)      Do you want to be part of discovering something new?

3)      Don’t know where to start?

If any of those aspects apply to you, it’s definitely worth hitting up DURS!

Duke Undergrads Sink Their Teeth into Evolution Research

Undergraduates Ben Schwartz (left) and Amalia Cong (center) have spent the past year studying enamel evolution in the labs of Christine Wall (right) and Greg Wray (not pictured).

Undergraduates Ben Schwartz (left) and Amalia Cong (center) have spent the past year studying enamel evolution in the labs of Christine Wall (right) and Greg Wray (not pictured).

By Erin Weeks

The evolution of thick tooth enamel helped turn our species into hard food-chomping omnivores, and two undergraduates are taking a bite out of research to unravel how that happened. Amalia Cong and Ben Schwartz are building on the work of a recent paper that identified precisely where in the human genome natural selection worked to give our species thick tooth enamel. The original study looked only at the potential role of four genes with a known role in tooth development — so now the team is broadening their scope.

“They’re really excited to expand out and push the envelope on new genes,” said Christine Wall, associate research professor of evolutionary anthropology and one of the authors of the paper, along with professor of biology Greg Wray.

Cong and Schwartz arrived in the Wall and Wray labs last summer through a special research session at Duke, the Howard Hughes Vertical Integration Partners (VIP) Program. For ten weeks, they received a crash course in primate evolutionary genomics.

“They had very little time, and the progress they made was astounding,” Wall said. “The success that they had is really a testament to how hard they worked. This has developed into their own research.”

“We’ve begun to expand our tooth enamel gene analysis to include proteins in conjunction with the RNA in order to gain a more holistic understanding of the evolutionary differences that exist between chimpanzees and humans,” Schwartz said. He will continue to work in the lab through this summer, turning the work into a senior thesis.

“One of our goals was to look at the relative expression of these few genes,” Schwartz said, which they’ve done by comparing tooth development in primates of different ages. “Our results correlated very heavily with known functions of these genes in other animals, such as rats.”

The experience has given both students a taste for research, which they hope to continue doing after graduating from Duke. Cong, who hails from a small city outside of Toronto, will be attending dental school in the fall, while Baltimore native Schwartz is interested in pursuing a joint MD/PhD.

Lawrence David Gets to the Gut of the Matter

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This “stream plot” is a running tally of various microbial populations in the gut over time.

By Karl Leif Bates

Assistant Professor Lawrence David of molecular genetics and microbiology in the Medical School, recently did a star turn on the Radio In Vivo program, talking about his work on the human gut’s incredible rainforest of microbial biodiversity and its interactions with infections, the immune system and our diets. There are ten non-you cells in your gut for every cell of you and their genes outnumber yours about 100 to one.

Lawrence David

Lawrence David

“Our guts are probably some of the world’s most densely colonized microbial communities,” David told host Ernie Hood. It’s a paradise really, with a steady supply of nutrients, constant climate, no sunlight “and only one way in and out.”

Listen to the one-hour April 30 podcast here

And then maybe take another 14 minutes to hear Lawrence absolutely kill at a  Story Colliders session in December 2012, telling the outrageous tale of sampling his own poop for a year and making it through airport security with a backpack full of um, specimens. (Warning – includes some pretty unavoidable scatalogical profanity.)

Discovering “CRISPR” methods for genetic recombination

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By Olivia Zhu

In a lecture to an overflowing auditorium in the Bryan Research Building on March 27th, Dr. Jennifer Doudna, of the University of California, Berkeley, unraveled her story of research into CRISPRs, or “clustered regularly interspaced short palindromic repeats.” Dr. Doudna specializes in RNA; she started her project on CRISPRs seven years ago, when CRISPRs were denounced as no more than junk.

The CRISPR method includes a modifiable RNA sequence whose function is to recognize target sequences on DNA. The RNA also includes a target sequence that induces cleavage by the associated protein, CAS9. CAS9 introduces double-stranded breaks and represents an exciting improvement over the previous, less efficient collection of nine proteins used to cleave DNA; the breaks make room for insertion of new genes. The CRISPR-CAS9 system has inserted genes into a wide range of organisms, including bacteria, yeast, nematode worms, fruit flies, plants, fish, mice, and even human cells.

Jennifer Doudna

Jennifer Doudna of UC Berkeley and the Howard Hughes Medical Institute

While researchers are actively investigating the possibility of using CRISPR technology to alter genes, Doudna said the mechanism behind CRISPR gene editing remains unclear. For example, it seems extraordinary that the CRISPR-CAS9 system can locate and unwind specific DNA sequences in human cells, as the DNA there is highly condensed around histones and methylated.

Doudna’s lab is working to understand the details of the CRISPR process. One current hypothesis includes the idea that there is a spring mechanism that allows the CAS9 protein to effectively cleave DNA strands.

Nevertheless, CRISPR technology has been instrumental in allowing more precise and efficient genetic modification. What we once considered junk has spurred substantial advances across various fields of science.

Stem Cells Might Tell Us Why Chimps Can’t Blush

Guest post by graduate student Sheena Faherty

Clint the Chimpanzee

Clint the chimpanzee was the first member of Pan troglodytes to have his DNA sequenced. Thanks, dude. (Photo from Yerkes National Primate Research Center.)

Clint the chimpanzee is at it again.

The first chimpanzee to have his genome sequenced in 2005 has now made another mammoth contribution to science, this time with his stem cells.

Using these stem cells, Greg Wray, professor in Biology and Evolutionary Anthropology and his former Ph.D. student, Lisa Pfefferle, recently published an article detailing an exciting new genomic tool that provides a sneak peek into how fundamental differences at the genetic level can lead to drastic differences we see at the outward level between humans and chimpanzees.

This fascinating new approach is based on a specific type of adult stem cells, known as adipose derived stromal cells (ASC). The beauty of ASCs is that they can be manipulated to morph into different types of mature cells. These cells can then be poked, prodded, and scrutinized under the microscope as a means to delve into fundamental questions regarding the molecular basis of human origins.

This work adds a powerful new tool to the field of comparative primate genomics. The goal is to discover the source of traits that set humans apart from other animals, like spoken language or the sole ability to blush when embarrassed.

By comparing humans with our closest genetic cousin, the chimpanzee, we can begin to uncover qualities unique to both humans and chimpanzees. These discoveries might lie within the genome.

Lisa Pfefferle developed a new technique, based on Clint's stem cells, to get at human-chimp differences. (Photo courtesy of Lisa Pfefferle.)

Lisa Pfefferle developed a new technique, based on Clint’s stem cells, to get at human-chimp differences. (Photo courtesy of Lisa Pfefferle.)

In a beautifully designed experiment, Wray and Pfefferle obtained a precious stock of Clint’s frozen ASCs, manipulated them into fat cells, known as adipocytes, and then compared his adipocytes with three different populations of human ASCs. (Clint, a resident of the Yerkes National Primate Research Center in Georgia, died at age 24 a few months before his genome was published.)

Using next-generation sequencing approaches, the researchers were then able to compare over 10,000 genes between human and chimpanzee. The results of this comparison show central differences within the set of genes that may be contributing to the obvious dissimilarities between humans and chimpanzees.

For example, genes controlling the development and function of the immune system were significantly higher in chimpanzees than in humans. It is well documented that chimpanzees are able to heal wounds faster than humans. This may be why.

In contrast, genes involved in the cell cycle and DNA processing, important for passing on genetic information and repairing DNA damage within cells, were expressed at a higher level in humans.

This novel approach of using ASCs in a controlled laboratory setting will undoubtedly be a valuable complement to existing studies on comparative primate genomics.

CITATION: Pfefferle, LW and Wray GA. Insights From a Chimpanzee Adipose Stromal Cell Population: Opportunities for Adult Stem Cells to Expand Primate Functional Genomics. October 2013: 1–18, doi:10.1093/gbe/evt148