Study on worm, mice fertility could lead to 'the pill' for men

Research led by biology professor Steven L'Hernault establishes a connection between fertilization in nematodes and mammals. (Emory Photo/Video)

By April Hunt

Someday, if women toast the discovery of male oral contraceptives, they may want to lift a glass to Emory biology professor Steven L'Hernault and his worms.

L'Hernault, chair of Emory College's Department of Biology, researched sperm proteins (not male hormones) in nematode worms. He and fellow researchers were able to establish a connection between fertilization in mammals, including humans, and nematodes. It was a highly unexpected outcome, given the two animal groups last shared a common ancestor about a billion years ago.

The conclusion, which some think could eventually lead to the equivalent of "the pill" for men, provides new insights on the basic mechanics of sperm and egg fertilization. It was recently reported in the journal Current Biology.

"At the end of the day, fertilization in humans seems to share some fundamental features with fertilization in worms," L'Hernault says. "Specifically, a similar protein is found on the sperm surface in humans and worms and, if a drug could be discovered that interfered with its function, we might be able to prevent sperm from fertilizing the egg.

"The worm may offer an inexpensive way to find such a drug," he adds. "Women have borne more than their fair share in that category of contraception, so the idea is to look at what might be possible for men."

In mammals, such as mice and humans, this protein is called Izumo, named for a shrine in Japan where newly married couples visit seeking luck in having children.

The Izumo equivalent in worms, named SPE-45, allows the sperm to be recognized by the egg, so that fertilization can occur. Without it, the sperm can move and do other processes normally, but they cannot fertilize the egg.

Worms with a mutation affecting SPE-45 are sterile. If you do "gene therapy" by expressing the worm SPE-45 protein in mutant worms, fertility is restored.

The challenge was to show that mammalian Izumo was functionally similar to SPE-45. L'Hernault says that he and his team of researchers worked for seven years, focusing on whether there was something specific that connected the two that allowed for fertilization.

Both SPE-45 and Izumo proteins have an Ig region that probably allows the sperm to adhere to the egg. Ig regions are widely found in many proteins of all animals, where they provide "stickiness" to proteins.

So, L'Hernault and his team took the Ig region from the mouse Izumo protein and used it to replace the Ig region in the worm SPE-45 protein, making a "hybrid" protein.

Surprisingly, this "hybrid" protein can be expressed in a worm SPE-45 mutant and it will partially restore fertility to the worm SPE-45 mutant.

In contrast, if the Ig domain from a worm skin protein is used to replace the Ig domain of the worm SPE-45 protein, this "hybrid" does not restore fertility.

In other words, not any Ig domain, with its associated "stickiness," will allow SPE-45 to fertilize an egg. It must be either the natural worm SPE-45 Ig domain or the Ig domain from a similar mammalian gene.

"One useful way to think about Ig domains is that they are all keys and, like real keys that look similar, some specifically open your house, while others only open your car," L'Hernault says. His research shows that the mouse Izumo and worm SPE-45 Ig domains are near-identical "keys."

All animals produce sperm that stick to and fertilize eggs from that species, but, generally, sperm from one animal cannot fertilize eggs from another species.

That means L'Hernault's work extends well beyond any potential connection to birth control and could provide more understanding on the basic underpinnings of fertility.

"Knowing how sperm stick to and fertilize eggs will provide key insights into what has changed and what has remained similar as animals have evolved," L'Hernault says.

 In addition to L'Hernault, the team and co-authors of the paper came from his lab and include Hitoshi Nishimura, Tatsuya Tajima, Heather Skye Comstra and Elizabeth J. Gleason.

Is your memory better than a chimpanzee's?

Slate ran an excerpt from the latest book by Emory primatologist Frans de Waal, "Are We Smart Enough to Know How Smart Animals Are?" De Waal describes how animals "keep surprising us" with their intelligence:

"There is the example of Ayumu, a young male chimpanzee at the Primate Research Institute of Kyoto University, in Japan. I watched Ayumu’s incredibly rapid decision-making on a touch screen the way I admire my students typing 10 times faster than me. In 2007, he managed to put human memory to shame by recalling a series of numbers from 1 through 9. He tapped them in the right order, even though the numbers appeared randomly on the screen and were quickly replaced by white squares. Having memorized the locations of all numbers, Ayumu touched the squares in the right order. Reducing the amount of time the numbers flashed on the screen didn’t bother him in the least, even though humans become less accurate the shorter the interval. Trying the task myself, I was unable to keep track of more than five numbers after staring at the screen for many seconds, while Ayumu did the same after having seen the numbers for just one-fifth of a second—literally the bat of an eye."

Read the full book excerpt at Slate.

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From the field to the Emory Herbarium: How knowledge of nature blooms

Graduate student Daniella Cicka, left, and senior Rina Lee, in the field in South Florida, collect a DNA sample from a plant species.

By Carol Clark

Adam Mackie will never look at a red maple the same way. “Native Americans made an infusion from the tree’s bark to treat gunshot wounds,” says Mackie, a senior majoring in biology. “It was also used to treat bug bites.”

Stachys floridana

Mackie is one of six Emory students who spent a recent alternative spring break in the field in rural South Florida. The students looked for plants used in indigenous medicine in the past, and collected specimens for the Emory Herbarium, under the guidance of medical ethnobotanist Cassandra Quave. They learned to identify endemic plant species in the wild, how to dig deep roots out of the thick mud of a marsh – even how to harvest and cook a swamp cabbage and make a mean guacamole.

"The best part was learning about plants from local people who knew how they were traditionally used," Mackie says.

Florida rancher Bob Brewer spent several days with the students in the field, introducing them to the gopher tortoise, a keystone species, and pointing out plants such as a thorny vine of smilax, which the locals call pipe briar.

We kept pulling and pulling on the stem," Mackie says, "and finally we got to this big tuber. He told us that old-timers used to hollow out these tubers to make pipes for smoking tobacco."

“Plants teach students to be more aware and appreciative of the natural world,” says Quave, a professor in Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology. Quave’s lab researches how traditional uses of plants can inform modern medicine. Interviews with traditional healers in rural Italy, for instance, led to her recent discovery that the leaves of the European chestnut tree contain ingredients with the power to disarm dangerous staph bacteria without boosting its drug resistance.

HERBARIUM NEEDS YOUR GREEN TO GROW

The Emory Herbarium, founded in 1949 by members of the biology department, was closed for decades, and its collection of more than 20,000 specimens was kept in storage. The facility, which recently reopened in the Rollins Research Center, needs $10,000 to help restore and annotate some of its damaged specimens, including rare plants in the Granite Rock Outcrop Collection, which grow in the vernal pools of Arabia Mountain and Stone Mountain. The funds will also support digitizing the specimens so they can be posted online and accessed from around the globe. Check out the Herbarium’s Momentum fundraising campaign to learn how to contribute.

A graduate of Emory herself, Quave found her career path after she went into the Peruvian Amazon as part of a tropical ecology class in the department of environmental sciences.

“When I first get students in the field, they look at a meadow and just see what looks like overgrown grass. It’s like they have blinders on,” Quave says. “Then the blinders come off and they begin to use their ‘plant goggles.’ They start seeing the world in a new way.”

Jennifer Ko, a freshman, grew up in Manhattan and considered herself a city girl. That view was broadened somewhat, as she recounted in a blog post about the trip on the Center for Human Health web site. “I am no longer scared of laying down on the grass and, by the end of the trip, even embraced dirt,” she wrote.

Seniors Jessie Cai and Rina Lee prepare to press an epiphytic air plant from the Bromeliaceae family for deposit in the Emory Herbarium.

Ko also learned to spot and collect specimens such as the frilly white plume of Saururus cernuus (lizard’s tail), deep in a swamp.

“The Choctaw and Creek Indians called this plant ‘widow’s medicine’ because they used it in a tea to help the bereaved get over their loss,” Quave says. She pulls a thick book, “Florida Ethnobotany,” off a shelf in her office to show a picture of widow’s medicine and a flattened sprig of yellow flowers falls out from the pages. “Oh, that’s a neat little Hypericum I collected,” she says, using the Latin name for St. John’s wort.

Ladyfinger bananas

The students rose before dawn and worked 12-hour days while in Florida. They explored scrub pine forests filled with 150-year old trees, still bearing what old-timers call “cat-facing” marks:” V-shapes cut into the bark during the 1800s to harvest turpentine. They took an airboat ride up the Peace River – the habitat of roseate spoonbills, bald eagles, alligators and other wildlife. They squelched in rubber boots through the mucky soil of cypress swamps, in search of species such as the Salyx willow tree, the original source of aspirin.

The group stayed in Quave’s hometown of Arcadia, in the home of her father, Raymond, who runs a business as a heavy equipment operator. “We shopped at a produce stand and bought gorgeous avocados and flats of the freshest, local strawberries to take home and prepare,” Quave says.

Ko cited time spent preparing food as one of the trip highlights. “In my 18 years of life, I never learned to cook,” she wrote in her blog post. “When Dr. Quave watched me struggle even cutting a tomato, she taught me all I needed to know to make my portion of dinner: The guacamole. She taught me the importance of a healthy meal, which is something I never fully understood. During the trip, I was forced to opt for the healthier choices and loved almost every meal I ate.”

Exploring the Peace River by airboat, from left: Cassandra Quave, Jessie Cai, Adam Mackie, Rina Lee, Jennifer Ko and Justin Robeny.

Raymond Quave showed the students how to chop down a swamp cabbage palm and pull the heart of it, then taught them how to boil the heart for their dinner, seasoned with milk, bacon and salt and pepper.

“As an educator I see many extraordinarily bright and talented students who have few outdoor survival skills,” Quave says. “I want them to appreciate the importance of different plants, for the health and sustenance of humans as well as ecosystems.”

The students brought back more than 170 species to add to the Emory Herbarium, which they will also help preserve and annotate.

Capsella bursa-pastoris

“It was an amazing experience,” Mackie said of the Florida trip. “I had worked in the Herbarium and in Dr. Quave’s lab, but that isn’t the same as learning about plants in the field. Now I’m able to grind and preserve some of the dried plant materials that I collected myself.”

Quave, who serves as curator of the Herbarium, spearheaded efforts to reopen it in 2012, after decades of neglect. She recently launched a fundraising campaign to restore some of the specimens and keep the facility in operation (see box, above).

The Herbarium’s original collection manager, Madeline Burbanck, who researched the rare and endangered plants on Georgia granite outcrop ecosystems, played a pivotal role in the official designation of Arabia Mountain as a National Heritage Area.

Tharanga Samarakoon, a plant scientist from Sri Lanka, now serves as the Herbarium’s collections manager, overseeing student volunteers who are working at restoration and digitization efforts.

“The Herbarium is not just a musty room filled with dried plants,” Quave says. “It’s a window into the natural world and a valuable resource for research and education, across disciplines. We need to not only maintain natural habitats, but collect and preserve plant specimens over time, to better understand and monitor ecosystems.”

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Celebrating math, miracles and a movie

The Carter Center hosted an advance screening of "The Man Who Knew Infinity." The gala celebrated the efforts of (from left): Samuel Pressman, of Pressman Films, the film's producer; Emory mathematician Ken Ono, an associate producer and math consultant for the film; Matthew Brown, the writer and director; and Devika Bhise, who portrays the mathematician Ramanujan’s wife, Janaki. (All photos by Becky Stein.)

By Carol Clark

“This is truly a joyful evening for me,” said Robin Forman, dean of Emory College of Arts and Sciences, at a special advance screening for Emory alumni of the film “The Man Who Knew Infinity.”

“First of all, I’m a mathematician,” Forman said, “and like every other mathematician, I’ve been waiting for this film to come out ever since I heard about it.”

The movie appeals, however, to a much broader audience. Hundreds of Emory alumni turned out for the private screening, held recently at the Carter Center. The evening was a chance to celebrate Emory’s connection to the film – Ken Ono, Asa Griggs Candler Professor of Math, served as an associate producer and the math consultant. The evening also celebrated how “miracles” of endurance, chance and unexpected human connections can overcome great odds to transform the world.

“The Man Who Knew Infinity,” to be released nationwide April 29, tells the true story of how a largely self-educated Indian named Srinivasa Ramanujan wrote to Cambridge mathematician G.H. Hardy in 1913, sparking an unlikely collaboration. The film stars Dev Patel and Jeremy Irons as Ramanujan and Hardy, whose “math bromance” spanned cultures and hierarchies to change math and science forever.

“What if Ramanujan had not reached out to Hardy?” Ono said in remarks before the screening. “The story of Ramanujan matters because science matters and imagination matters.”



He announced plans for a global contest called “The Spirit of Ramanujan Math Talent Search.” In partnership with the film’s producers – IFC Films and Pressman films – the American Mathematical Society (AMS) and Carnegie Mellon mathematician Po-Shen Loh, Ono will seek hidden math talent and match it to opportunities for advancement.

“Ramanujan represents untapped potential that we must believe in,” Ono said. “In that spirit, our goal is to scour the villages, towns and cities of the world in search of undiscovered talent.”

Just before World War I, Hardy invited Ramanujan to leave rural India and come to Cambridge University in England. Hardy helped guide the unfathomable genius of Ramanujan – who said his fantastic math formulas came to him as visions from a Hindu goddess. Hardy ensured that Ramanujan’s discoveries had lasting impact, and he lobbied to have him elected as a fellow at Trinity College, where Isaac Newton studied.

After watching the story unfold on the screen, audience members asked questions and provided feedback to a panel that flew in for the event, including Matthew Brown, the writer and director; Devika Bhise, who portrays Ramanujan’s wife, Janaki; and Samuel Pressman, a creative consultant for Pressman Films.

“To be here tonight with you all at the Carter Center is a miracle,” Brown said. “This project has been 10 years in the making. It was a true independent film, made on a really tight budget.”

Matthew Brown and Devika Bhise took questions from the audience following the screening. "This movie is very important to me," said Bhise, who portrayed Ramanujan's wife.

The film takes its name and inspiration from a 1992 biography of Ramanujan by Robert Kanigel. Brown said he first picked up the book while visiting an aunt, who happened to be reading it for her book club, and he became captivated by the story. Hardy was an atheist and life-long bachelor with few close relationships. Ramanujan, on the other hand, was married, devoted to his family and extremely religious. He wrote that an equation had no meaning to him unless it was the thought of god.

“It was a miracle that Ramanujan came to Cambridge, and that Hardy took a chance on him,” Brown said. “I found the human aspect to be unbelievable, never mind the genius aspect. It was quite a story to jump into as a filmmaker.”

Brown was given Ono’s name as a Ramanujan expert who might be able to help keep the details right during filming. Ono is a number theorist who has solved many of the mysteries left behind by Ramanujan, revealing how his work relates to concepts that were largely unknown during his day, such as string theory and black holes.

“I emailed Ken,” Brown recalled, “and he was on an airplane within two days to be on set. Ken was our main man. He set all the math straight.” Brown said that his passion for filmmaking was more than matched by Ono’s passion for math.

“Congratulations on an exceedingly beautiful film,” one audience member told the panel. He added that he found Bhise’s portrayal of Janaki particularly moving.

Carnegie Mellon mathematician Po-Shen Loh joined the panel on stage to discuss plans for a global contest called “The Spirit of Ramanujan Math Talent Search.”

Ramanujan had to leave his young wife behind in India to go to England and collaborate with Hardy. The harsh English climate combined with war-time rationing and Ramanujan’s strict vegetarian diet took their toll. He contracted tuberculosis while at Cambridge and died at age 32, a year after returning to India. In keeping with tradition, Janaki never remarried. She endured familial abandonment and poverty but strived to keep the legacy of her husband’s work alive.

“Obviously, this movie is very important to me,” Bhise said. “When you play a real human being, you have to do her life justice. Even though she didn’t understand the math produced by her husband, she understood the artistry, the passion and the genius underlying it.”

Sam Pressman said he gained a similar insight working on the film. “I never realized the beauty of math, and that the ideas of math are like art,” he said. “Our education system chooses to focus on the building blocks of mathematics. But there’s another way to think of math and we want to invite the world to appreciate it.”

Mathematician Po-Shen Loh and Mike Breen, from the AMS, joined the panel to discuss the plans for The Spirit of Ramanujan Math Talent Search. The contest will connect with youth through Expii.com, a new smart phone friendly learning platform that delivers math quizzes and instruction. Loh developed the software as part of his role as coach for the 2015 USA International Math Olympiad team – the first U.S. team to take gold in 21 years.

“Everyone with a smart phone can benefit from this interactive teaching system,” Loh said. “Our purpose is to reach out across the world and try to find the next Ramanujan.”

The movie and the talent search are a chance to “think about math in a fun way,” Breen said. “Perhaps the best way to generate interest and amazing performances in math might be to fuse math and entertainment.”

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