Duke Research Blog

Following the people and events that make up the research community at Duke.

Category: Biology (Page 2 of 28)

Scientists Engineer Disease-Resistant Rice Without Sacrificing Yield

Researchers have developed a way to make rice more resistant to bacterial blight and other diseases without reducing yield. Photo by Max Pixel.

Researchers have successfully developed a novel method that allows for increased disease resistance in rice without decreasing yield. A team at Duke University, working in collaboration with scientists at Huazhong Agricultural University in China, describe the findings in a paper published May 17, 2017 in the journal Nature.

Rice is one of the most important staple crops, responsible for providing over one-fifth of the calories consumed by humans worldwide. Diseases caused by bacterial or fungal pathogens present a significant problem, and can result in the loss of 80 percent or more of a rice crop.

Decades of research into the plant immune response have identified components that can be used to engineer disease-resistant plants. However, their practical application to crops is limited due to the decreased yield associated with a constantly active defense response.

“Immunity is a double-edged sword, ” said study co-author Xinnian Dong, professor of biology at Duke and lead investigator of the study. “There is often a tradeoff between growth and defense because defense proteins are not only toxic to pathogens but also harmful to self when overexpressed,” Dong said. “This is a major challenge in engineering disease resistance for agricultural use because the ultimate goal is to protect the yield.”

Previous studies have focused on altering the coding sequence or upstream DNA sequence elements of a gene. These upstream DNA elements are known as promoters, and they act as switches that turn on or off a gene’s expression. This is the first step of a gene’s synthesis into its protein product, known as transcription.

By attaching a promoter that gives an “on” signal to a defense gene, a plant can be engineered to be highly resistant to pathogens, though at a cost to growth and yield. These costs can be partially alleviated by attaching the defense gene to a “pathogen specific” promoter that turns on in the presence of pathogen attack.

To further alleviate the negative effects of active defense, the Dong group sought to add an additional layer of control. They turned newly discovered sequence elements, called upstream open reading frames (uORFs), to help address this problem. These sequence elements act on the intermediate of a gene, or messenger (RNA, a molecule similar to DNA) to govern its “translation” into the final protein product. A recent study by the Dong lab in an accompanying paper in Nature has identified many of these elements that respond in a pathogen-inducible manner.

The Dong group hypothesized that adding this pathogen-inducible translational regulation would result in a tighter control of defense protein expression and minimize the lost yield associated with enhanced disease resistance.

To test this hypothesis, the researchers started with Arabidopsis, a flowering plant commonly used in laboratory research. They created a DNA sequence that contains both the transcriptional and translational elements (uORFs) and fused them upstream of the potent “immune activator” gene called snc1. This hybrid sequence was called a “transcriptional/translational cassette” and was inserted into Arabidopsis plants.

When plants have snc1 constitutively active, they are highly resistant to pathogens, but have severely stunted growth. Strikingly, plants with the transcriptional/translational cassette not only have increased resistance, but they also lacked growth defects and resembled healthy wild-type plants. These results show the benefits of adding translational control in engineering plants that have increased resistance without significant costs.

The Dong group then sought to apply these findings to engineer disease-resistant rice, as it is one of the world’s most important crops. They created transgenic rice lines containing the transcriptional/translational cassette driving expression of another potent “immune activator” gene called AtNPR1. This gene was chosen as it has been found to confer broad spectrum pathogen resistance in a wide variety of crop species, including rice, citrus, apple and wheat.

The dry yellowish leaves on these rice plants are a classic symptom of bacterial blight, a devastating disease that affects rice fields worldwide. Photo by Meng Yuan.

The transgenic rice lines containing the transcriptional/translational cassette were infected with bacterial/fungal pathogens that cause three major rice diseases — rice  blight, leaf streak, and fungal blast. These showed high resistance to all three pathogens, indicating broad spectrum resistance could be achieved. Importantly, when grown in the field, their yield — both in terms of grain quantity and quality per plant — was almost unaffected. These results indicate a great potential for agricultural applications.

This strategy is the first known use of adding translational control for the engineering of disease-resistant crops with minimal yield costs. It has many advantages, as it is broadly applicable to a variety of crop species against many pathogens. Since this strategy involves activating the plants’ endogenous defenses, it may also reduce the use of pesticides on crops and hence protect the environment.

Additionally, these findings may be broadly applicable to other systems as well. These upstream elements (uORFs) are widely present in organisms from yeast to humans, with nearly half of all human transcripts containing them. “The great potential in using these elements in controlling protein translation during specific biological processes has yet to be realized,” Dong said.

Corresponding author Xinnian Dong can be reached at xdong@duke.edu or (919) 613-8176.

CITATION:  “uORF-Mediated Translation Allows Engineered Plant Disease Resistance Without Fitness Costs,” Guoyong Xu, Meng Yuan,   Chaoren Ai, Lijing Liu, Edward Zhuang, Sargis Karapetyan, Shiping Wang and Xinnian Dong. Nature, May 17, 2017. DOI: 10.1038/nature22372

 

Guest post by Jonathan Motley

Where Some Ski, Others Do Science

For most people, Lost Trail is a ski spot located at 7,000 feet in the Rocky Mountains on the border of Idaho and Montana. Skiers and snowboarders descend down steep slopes, past forests and alpine meadows that get more than 25 feet of snow each year. But for a team of researchers led by Duke biology professor Thomas Mitchell-Olds, buried beneath the snow is a hidden population of native plants on the cusp of dividing into two new species.

Molly Rivera-Olds shovels snow at Lost Trail Pass.

Studying a spindly North American wildflower called Boechera stricta, Mitchell-Olds and colleagues suspected that a process called chromosomal inversion — in which part of a chromosome breaks off and reattaches itself upside down — plays a central role in speciation. To test the idea, they planted Boechera stricta seedlings in a mountaintop meadow near the Lost Trail resort.

To reach the meadow, the researchers carried thousands of seedlings up the mountain in specially constructed backpacks. They also lugged up nine empty garbage cans and filled them with snow to water the plants throughout the summer.

Once the seedlings matured, the researchers measured flowering time, seed production, and survival. They found that plants with the chromosomal inversion had a leg up on the steep slopes of the Rocky Mountains. Eventually, the researchers say, this can lead to plants with the inverted DNA splitting off and forming a new species.

The findings were published April 3, 2017 in the journal Nature Ecology & Evolution.

# # #

CITATION:  “Young Inversion with Multiple Linked QTLs Under Selection in a Hybrid Zone,” Cheng-Ruei Lee, Baosheng Wang et al. Nature Ecology & Evolution, April 3, 2017. DOI:10.1038/s41559-017-0119.

Guest post by Molly Rivera-Olds

 

 

 

 

 

From Sunfish-Seeker to Planet-Saver: Dr. Tierney Thys

Marine biologist Tierney Thys believes that science make us superheroes. In her words, the tools of science are the superpowers that “allow us to explore worlds that are invisible to the naked eye.”

As a National Geographic Explorer, Research Associate at the California Academy of Sciences, and, in my humble opinion, one of the most effective, passionate science communicators out there, she may as well be a superhero already.

Dr. Tierney Thys snorkels with some aquatic research subjects. Photo credit: Tierney Thys.

Thys, an alumna of Duke’s Biology Department, presented at the Marine Science and Conservation Leaders’ (MSCL) inaugural Marine Science Symposium on Saturday, March 25. She was one of four featured speakers — all women in STEM— whose research interests range from marine biology to physical oceanography.

Though she discussed her own research and life story in depth, the main point Thys drove home was the importance of (and science behind) powerful science communication.

Like most marine biologists, Thys’ love for the ocean began when she was a child. She received her Ph.D. from Duke in 1998, an endeavor which, she said, “looked interminable while [she] was in the midst of grad school but, in retrospect, was just a blink of an eye.”

Among the many fun tidbits she has gleaned studying ocean science are the following:

  • As adults, humans retain a lot of characteristics from our fish-like time in the womb; e.g. “we can thank fish for washboard abs.”
  • Humans, for all our obsession with large brains, have nothing on the African elephantfish, which has a “higher brain weight to body weight ratio than any other vertebrate.”
  • Fish had the gender continuum “totally nailed” before it became trendy among humans, with fish of many species having the ability to change sex at will.

Thys, right, and her dissertation advisor, Dr. Stephen Wainwright, left. Photo credit: Tierney Thys.

Her most impactful lesson out of Duke, however, came from her dissertation advisor Stephen Wainwright, James B. Duke Professor emeritus of zoology. Wainwright is the founder of Duke’s Bio-Design Studio, an art studio within a scientific research laboratory employing a full-time sculptor “to create three-dimensional working models of biological systems for research,” as reported by Duke Magazine. Exposure to this unique melding of disciplines in the final stages of Thys’ education set her on what she said was “an eclectic career path” that would also seek to fuse the artistic and the scientific.

Thys’ research specialty out of graduate school is the Mola mola, more commonly known as the Ocean sunfish—the heaviest bony fish on the planet. According to Thys, sunfish can grow to “60 million times their starting weight,” the equivalent of a human child growing to the weight of six Titanic ships. The heaviest Mola ever caught weighed over 5000 lbs., though, surprisingly, jellies (what most folks would call jellyfish) comprise most of the adult sunfish’s diet.

Thys hailed pop-off satellite tags as the “superpower” of science that allows her to track sunfish through the world ocean, generating data that can improve environmental protection of the species.

A fun graphic Thys used in her presentation to explain the technology of pop-off tags for tracking Mola mola, pictured right. Photo credit: Mike Johnson.

“Studying the sunfish has eclipsed studying any other fish for me. [They’re ] a massive part of the bycatch in driftnet fisheries all over the world—[but] we need to keep our jelly-eaters intact. With data, we can figure out the [sunfish] hotspots, and work to protect those areas,” Thys said.

Thys has tackled this problem herself by adapting the discipline-blending approach of her advisor, Wainwright. She has primarily used filmmaking to bridge the gap between the arts and sciences, playing key roles in high-profile documentary projects meant to improve public understanding of marine science, technology, and conservation. These include the Strange Days on Planet Earth series with National Geographic, The Shape of Life series with PBS, and several short documentary films. She has also collaborated with dance companies to create conservation-oriented dance productions, K-6 schools for educational art projects, and prisons to improve inmates’ scientific literacy with nature imagery—all to widen the scope of her science-education efforts. Thys supports her creative ideas with science itself:

“One very large filter exists between our conscious mind and subconscious mind, she said. “Our conscious mind can only process a tiny amount of the information gathered by our subconscious mind.”

“A good story can cut through these filters and light up our brains in new ways,” Thys said “By using different forms of art to tell stories infused with scientific information, we can message in profound ways. We can reach people who might not otherwise be interested or receptive to science. The arts are not a luxury, but rather a powerful vehicle for helping message, teach and share our vital scientific findings,” Thys said.

A mural Thys made with students out of bottle caps at a California elementary school, one of Thys’ many efforts to spread public awareness of scientific issues. Photo credit: Tierney Thys.

As though she hadn’t already empowered everyone in the audience to save the world, Thys concluded with a compelling piece of advice: “Be a part of something much bigger than yourself.”

Post by Maya Iskandarani

Closing the Funding Gap for Minority Scientists

DURHAM, N.C. — The barriers to minority students in science, technology, engineering and math (STEM) don’t go away once they’ve finished school and landed a job, studies show. But one nationwide initiative aims to level the playing field once they get there.

With support from a 3-year, $500,0000 grant from the National Science Foundation, assistant professors and postdoctoral fellows who come from underrepresented minorities are encouraged to apply by May 5 for a free grant writing workshop to be held June 22-24 in Washington, D.C..

It’s no secret that STEM has a diversity problem. In 2015, African-Americans and Latinos made up 29 percent of the U.S. workforce, but only 11 percent of scientists and engineers.

A study published in the journal Science in 2011 revealed that minority scientists also were less likely to win grants from the National Institutes of Health, the largest source of research funding to universities.

Based on an analysis of 83,000 grant applications from 2000 to 2006, the study authors found that applications from black researchers were 13 percent less likely to succeed than applications from their white peers. Applications from Asian and Hispanic scientists were 5 and 3 percent less likely to be awarded, respectively.

Even when the study authors made sure they were comparing applicants with similar educational backgrounds, training, employers and publication records, the funding gap persisted — particularly for African-Americans.

Competition for federal research dollars is already tough. But white scientists won 29 percent of the time, and black scientists succeeded only 16 percent of the time.

Pennsylvania State University chemistry professor Squire Booker is co-principal investigator of a $500,000 initiative funded by the National Science Foundation to help underrepresented minority scientists write winning research grants.

“That report sent a shock wave through the scientific community,” said Squire Booker, a Howard Hughes Medical Institute investigator and chemistry professor at Pennsylvania State University. Speaking last week in the Nanaline H. Duke building on Duke’s Research Drive, Booker outlined a mentoring initiative that aims to close the gap.

In 2013, Booker and colleagues on the Minority Affairs Committee of the American Society for Biochemistry and Molecular Biology decided to host a workshop to demystify the grant application process and help minority scientists write winning grants.

Grant success is key to making it in academia. Even at universities that don’t make funding a formal requirement for tenure and promotion, research is expensive. Outside funding is often required to keep a lab going, and research productivity — generating data and publishing results — is critical.

To insure underrepresented minorities have every chance to compete for increasingly tight federal research dollars, Booker and colleagues developed the Interactive Mentoring Activities for Grantsmanship Enhancement program, known as IMAGE. Program officers from NIH and NSF offer tips on navigating the funding process, crafting a successful proposal, decoding reviews and revising and resubmitting. The organizers also stage a mock review panel, and participants receive real-time, constructive feedback on potential research proposals.

Participants include researchers in biology, biophysics, biochemistry and molecular biology. More than half of the program’s 130 alumni have been awarded NSF or NIH grants since the workshop series started in 2013.

Booker anticipates this year’s program will include more postdoctoral fellows. “Now we’re trying to expand the program to intervene at an earlier stage,” Booker said.

To apply for the 2017 workshop visit http://www.asbmb.org/grantwriting/.  The application deadline is May 5.

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Post by Robin Smith

The Road to a Tastier Tomato

This week, I discovered that I’ve lived life deprived of a good tomato.

As a tomato-lover, I was surprised to learn from Professor Harry Klee of the University of Florida that the supermarket tomatoes I’ve enjoyed throughout my 18-year existence are all flavorless compared to the tomatoes of the past. He spoke at Duke as a guest of the University Program in Genetics and Genomics on Feb. 28.

It turns out that commercial tomato growers, by breeding more profitable (i.e. higher-yield, redder-color, larger-fruit) tomato varieties over the past 50 years, inadvertently excluded what Klee believes is the most important tomato trait of all:

Commercial tomato growers have bred larger, redder tomatoes that are less flavorful than heirloom and older varieties. Image courtesy of Harry Klee.

Flavor.

Apparently, I was one of very few people unaware of this issue. The public outcry in response to the increasing flavorlessness of commercial tomatoes began over a decade ago, when Klee first began to study tomato genetics.

From his research, Klee has drawn several important, unexpected conclusions, chief among them:

1: Flavor has more to do with smell than taste;

2: Lesser-known biochemical compounds called “volatiles” influence the flavor of tomatoes more than sugars, acids, and other well-known, larger compounds;

3: These “volatiles” are less present in modern tomato varieties than in tastier, older, and heirloom varieties;

But fear not—

4: Tomatoes can be back-bred to regain the genes that code for volatile compounds.

In other words, Klee has mapped the way back to the flavorful tomatoes of the past. His work culminated in a cover story of the Jan. 27 issue of Science. The corresponding paper describing the analysis of over 300 tomato strains to identify the chemicals associated with “good” and “bad” tomatoes.

Dr. Harry Klee and collaborators in his lab at the University of Florida. Image courtesy of Harry Klee.

To prove that modern tomatoes have less of the compounds that make them tasty, Klee and his team recruited a panel of 100 taste-testers to rank 160 representative tomato varieties. According to Klee, the team “developed statistical models to explain the chemistry of ‘liking’ [tomatoes],” then narrowed down the list of compounds that correlated with “liking” from 400 to 26. After tracing these 26 compounds to genetic loci, they used whole-genome sequencing to show that these loci are less expressed in modern tomatoes than in “cerasiforme” (i.e. old) and heirloom tomato varieties.

Further studies showed that tomato weight is inversely correlated with sugar content—in other words, “a gigantic fruit doesn’t taste as good,” Klee said.

If Klee can convince tomato growers that consumers value flavor over size, color, and quantity, then he might just single-handedly put flavorful tomatoes back on the shelves. Nevertheless—and despite the publicity surrounding his work—Klee understands it make take a while before commercial tomato growers see the light.

Klee and his team of scientists have genetically mapped the way back to the tasty tomatoes of the past. Image courtesy of Harry Klee.

“Growers get no more money if the tomato tastes good or bad; they’re paid for how many pounds of red objects they put in a box…[but] we can’t just blame the modern breeders. We’ve been selecting bigger and bigger fruit for millennia, and that has come at the cost of reducing flavor,” Klee said.

Post by Maya Iskandarani

Cells Need Their Personal Space

One of the body’s first lines of defense against harmful pathogens is the skin. The constant maintenance of this epithelial cell layer which serves as a barrier to infection  is essential to fighting off disease.

Jody Rosenblatt, an Associate Professor in the Department of Oncological Sciences at the University of Utah School of Medicine, has made it her lab’s mission to study the function of epithelia as a barrier, how this barrier is maintained, and what happens when it goes awry.

Jody Rosenblatt, PhD is an investigator for the Huntsman Cancer Institute at the University of Utah School of Medicine and a Howard Hughes Medical Institute Faculty Scholar

Rosenblatt recently spoke at Duke’s Developmental & Stem Cell Biology Colloquium where she presented some extraordinary findings about how epithelia can squeeze out  both healthy and dying cells  to preserve the protective barrier.

Some c cells commit suicide via programed cell death and are forced out of the cell layer because they are no longer functional. But in the case of forcing out living cells, “cell extrusion is more like a homicide” said Rosenblatt. The fact that perfectly functional living cells are pushed out of a cell layer perplexed her group until they discovered it was happening as a response to cell overcrowding.

Rosenblatt explained that like people, cells tend to like their personal space, so when this is compromised, live cells are actively pushed out of the cell layer, restoring balanced cell numbers.

Rosenblatt’s lab took this discovery a step farther and pinpointed the pathway that likely induces the extrusion of live cells.

Piezo1, a stretch-activated calcium ion channel present in epithelial cells, senses crowding and activates sphingosine-1-phosphate (S1P), the driver of epithelial cell extrusion. When Piezo1 channels are inhibited and don’t sense stretching, cells cannot extrude.

Using zebrafish, Rosenblatt showed that when extrusion was blocked by compromising the S1P2 pathway, epidermal cells form masses that are resistant to chemotherapy drugs and signals for programmed cell death.

Rosenblatt explains the importance of regulating cell extrusion in the epithelium to maintain the tissue’s function as a protective barrier for our organs. Misregulation of this function can result in diseases such as metastatic cancers.

This finding lead them to examine samples of human pancreatic, lung, colon, and breast tumors. They found that in all of these cancers, S1P2 is significantly reduced. But if they restored S1P2 activity in cell lines of these cancers, the extrusion pathway was rescued and tumor size and metastases were greatly decreased!

Rosenblatt and her colleagues have shown that the importance of cell extrusion cannot be overstated. If extrusion is compromised, cells can begin to pile up and move beneath the cell layer, which can lead to invasion of the tissues beneath the epithelium and metastasis to other sites in the body.

Now that we are uncovering more of the pathways involved in tumor formation and metastasis, we can develop new drugs that may be the key to fighting these devastating diseases.

Guest Post by Amanda Cox, PhD candidate in biology

 

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