Triboelectric nanogenerators (TENG) convert mechanical energy harvested from the environment to electricity for powering small devices such as sensors or for recharging consumer electronics. Now, researchers have harnessed these devices to improve the charging of molecules in a way that dramatically boosts the sensitivity of a widely-used chemical analysis technique.
Researchers at the Georgia Institute of Technology have shown that replacing conventional power supplies with TENG devices for charging the molecules being analyzed can boost the sensitivity of mass spectrometers to unprecedented levels. The improvement also allows identification to be done with smaller sample volumes, potentially conserving precious biomolecules or chemical mixtures that may be available only in minute quantities.
Though the mechanism by which the enhancement takes place requires more study, the researchers believe the unique aspects of the TENG output – oscillating high voltage and controlled current – allow improvements in the ionization process, increasing the voltage applied without damaging samples or the instrument. The research, which was supported by the National Science Foundation, NASA Astrobiology Program and the Department of Energy, is reported February 27 in the journal Nature Nanotechnology.
“Our discovery is basically a new and very controlled way of putting charge onto molecules,” said Facundo Fernández, a professor in Georgia Tech’s School of Chemistry and Biochemistry who uses mass spectrometry to study everything from small drug molecules to large proteins. "We know exactly how much charge we produce using these nanogenerators, allowing us to reach sensitivity levels that are unheard-of – at the zeptomole scale. We can measure down to literally hundreds of molecules without tagging.”
Fernández and his research team worked with Zhong Lin Wang, a pioneer in developing the TENG technology. Wang, a Regents professor in Georgia Tech’s School of Materials Science and Engineering, said the TENGs provide consistent charging levels that produce quantized ion pulses of adjustable duration, polarity and frequency.
“The key here is that the total charge delivered in each cycle is entirely controlled and constant regardless of the speed at which the TENG is triggered,” said Wang, who holds the Hightower Chair in the School of Materials Science and Engineering. “This is a new direction for the triboelectric nanogenerators and opens a door for using the technology in the design of future instrumentation and equipment. This research demonstrates another practical impact of TENG technology.”
Mass spectrometry measures the mass-to-charge ratio of ions to identify and quantify molecules in both simple and complex mixtures. The technology is used across a broad range of scientific fields and applications, with molecules ranging from small drug compounds on up to large biomolecules. Mass spectrometry is used in biomedicine, food science, homeland security, systems biology, drug discovery and other areas.
But in conventional electrospray mass spec techniques, as much as 99 percent of the sample can be wasted during ionization, said Fernández, who holds the Vasser Woolley Foundation Chair in Bioanalytical Chemistry. That’s largely because in conventional systems, the mass analysis process is pulsed or scanned, while the ionization of samples is continuous. The new TENG pulsed power source allows scientists to time the ionization to match what’s happening inside the mass spectrometer, specifically within a component known as the mass analyzer.
Beyond improved sensitivity and the ability to analyze very small sample quantities, the new technique also allows ion deposition on surfaces, even non-conducting ones. That’s because the oscillating ionization produces a sequence of alternating positive and negative charges, producing a net neutral surface, Fernández said.
Mass spectrometers require large amounts of power for creating the vacuum essential to measuring the mass-to-charge ratio of each molecule. While it’s possible that future TENG devices could power an entire miniature mass spectrometer, the TENG devices are now used just to ionize samples.
“The nanogenerators could eliminate a big chunk of the mass spectrometer system because they wouldn’t need a more powerful device for making the ions,” Fernández said. “This could be particularly applicable to conditions that are extreme and harsh, such as on a battlefield or in space, where you would need a very robust and self-contained unit.”
Triboelectric nanogenerators, developed by Wang in 2012, use a combination of the triboelectric effect and electrostatic induction to generate small amounts of electrical power from mechanical motion such as rotation, sliding or vibration. The triboelectric effect takes advantage of the fact that certain materials become electrically charged after they come into moving contact with a surface made from a different material. Wang and his research team have developed TENGs with four different working modes, including a rotating disc that may be ideal for high throughput mass spectrometry experiments. This paper is the first publication about an application of TENG to an advanced instrument.
Wang’s team has measured voltage levels at the mass spec ionizer of between 6,000 and 8,000 volts. Standard ionizers normally operate at less than 1,500 volts. The technology has been used with both electrospray ionization and plasma discharge ionization, with the flexibility of generating single polarity or alternating polarity ion pulses.
“Because the voltage from these nanogenerators is high, we believe that the size of the sample droplets can be much smaller than with the conventional way of making ions,” Fernández said. “That increases the ion generation efficiency. We are operating in a completely different electrospray regime, and it could completely change the way this technology is used.”
The TENG technology could be retrofitted to existing mass spectrometers, as Fernández has already done in his lab. With publication of the journal article, he hopes other labs will start exploring use of the TENG devices in mass spectrometry and other areas. “I see potential not only in analytical chemistry, but also in synthesis, electrochemistry and other areas that require a controlled way of producing electrical charges,” Fernández said.
The research was initiated by postdoctoral fellows in the two laboratory groups, Anyin Li and Yunlong Zi. “This project really shows how innovation can happen at the boundaries between different disciplines when scientists are free to pursue new ideas,” Fernández added.
This work was jointly supported by NSF and the NASA Astrobiology Program, under the NSF Center for Chemical Evolution, CHE-1504217. Research was also supported by the U.S. Department of Energy, Office of Energy Sciences (Award DE-FG02-07ER46394), and the National Science Foundation (DMR-1505319). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the sponsors.
CITATION: Anyin Li, Yunlong Zi, Hengyu Guo, Zhong Lin Wang, Facundo M. Fernández, “Triboelectric Nanogenerators for Sensitive Nano-Coulomb Molecular Mass Spectrometry,” (Nature Nanotechnology, 2016). http://dx.doi.org/10.1038/nnano.2017.17
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The 25th annual Suddath Symposium was devoted, for the first time, to neuroscience research. The two-day event (Feb. 21-22) featured speakers from across the country and both sides of the Atlantic – some of the world’s thought-leaders in the budding field.
But it was a young, recently-minted Ph.D. in the area of chemical and biomolecular engineering who took center stage as the event unfolded. Suddath Award winner Christine He, from the lab of Petit Institute researcher Martha Grover, and with one foot out the door, delivered the first presentation of the symposium, and it had nothing to do with neuroscience.
Such is the nature of this well-attended, wide-ranging event. At the end of every calendar year, a doctoral student is selected as the Suddath Award winner, for having demonstrated a significant research achievement in biology, biochemistry, or biomedical engineering. In addition to the $1,000 first prize, the winner also is invited to present his or her research at the annual Suddath Symposium, regardless of whether or not it matches with the symposium’s selected theme.
He, the seventh woman in a row to earn the honor, presented her research project (entitled, “Building a Model Prebiotic Nucleic Acid Replication Cycle in Viscous Enivornments.”). And even though it was not about neuroscience, her presentation – delivered with the calmness of a seasoned pro – drew a packed room.
“I wasn’t really sure what to expect, so I was very pleased with the turnout,” said He, who opened the two-day symposium on Tuesday, then caught a plane Wednesday morning for her new assignment as a post-doc at the University of California-Berkeley, where she’ll be working in the lab of Jennifer Doudna, the scientist who co-invented pioneering new technology for editing genes, called CRISPR-Cas9.
“This is going to be exciting,” He said Tuesday evening, shortly before leaving for the next phase of her life.
Meanwhile, the neuroscientists and neuro-engineers kept packing the Suddath Room on the ground floor of the Petit Institute.
“This is an exciting time in neuroscience. Things are rapidly expanding in the field, especially here at Georgia Tech,” said Garrett Stanley, co-director of this year’s symposium with Hang Lu. Both are Petit Institute researchers.
Stanley is professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, and Lu is a professor in Georgia Tech’s School of Chemical and Biochemical Engineering), both of them busily engaged in neuroscience research and members of the GTNeuro steering committee (GTNeuro is the umbrella organization of Georgia Tech’s neuro-community).
Featured researchers from out of town were Eve Marder (Brandeis University), Gero Miesenböck (University of Oxford, England), Vincent Pieribone (Yale University), William Shafer (Cambridge University, England), and Mark Schnitzer (Stanford University).
Researchers from the Atlanta area were Gordon Berman (Emory University), Bilal Haider (Coulter Department at Emory/Georgia Tech), Liang Han (Georgia Tech), Ravi Kane (Georgia Tech), Paul Katz (Georgia State University), Robert Liu (Emory), Patrick McGrath (Georgia Tech), Annabelle Singer (Coulter Department at Emory/Georgia Tech), Sam Sober (Emory), Zhexing Wen (Emory), and Larry Young (Emory).
“The goal is to highlight some of the excitement of neuroscience and neuro-technology from our community, but also to talk to non-neuroscientists and get them excited,” said Stanley. “So we brought in people from across the U.S. and abroad, an exciting array of speakers. I think the interest and attendance at this symposium is a reflection of the growing interest in the field. And really, we’re just getting started.”
LINKS:
2017 Suddath Symposium program
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Parker H. Petit Institute for
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David M. Collard is the recipient of the 2017 Felton Jenkins, Jr. Hall of Fame Faculty Award for the research and comprehensive universities sector of the University System of Georgia (USG). The award, which invites nominations from across USG, recognizes a faculty member for strong commitment to teaching and student success.
Collard is a professor in the School of Chemistry and Biochemistry and the associate dean for academic programs in the College of Sciences.
According to the award review committee, Collard is “an exemplar for combining the best of teaching and research” at a research institution. Collard’s selection for the award was unanimous, according to USG.
“I speak for the entire College when I congratulate David on this USG recognition of his accomplishments and thank him for his extraordinary partnership,” says College of Sciences Dean Paul M. Goldbart.
Among Collard’s many outstanding accomplishments, the USG review committee singled out his use of active-learning approaches and educational technology. Collard has also established a number of on-campus experiential learning programs. These have engaged more than a thousand students in undergraduate research, financial aid scholarships, and living-learning communities.
“Our programs today would be unrecognizable if you removed David’s contributions,” says M.G. Finn, the chair of the School of Chemistry and Biochemistry. “What we teach, how we teach it, what facilities we use to do so, and what advanced opportunities are available to our students all bear the Collard stamp.”
Also noted by the review committee was Collard’s work as co-director of the Chemistry Collaborations, Workshops & Communities of Scholars (cCWCS) program. The program, which is funded by the National Science Foundation, offers workshops that put professors back in the classroom to learn or relearn material in new contexts. cCWCS encourages best practices in science, technology, engineering, and mathematics (STEM) education for all instructors, the committee noted. The program’s workshops have engaged more than 3,000 faculty members from more than 800 U.S. institutions.
“In the development of undergraduate programs, David’s sharp strategic vision has led to several game-changing moves for the College,” Goldbart says. Examples are the creation of the science-oriented SMaRT and SHaRP living-learning communities, the planning for the B.S. in Neuroscience degree, and the cultivation of a strong partnership with the Georgia Tech Office of Admissions, which has yielded strong strides in undergraduate enrollment. “David’s multidimensional leadership,” Goldbart says, “continues to be crucial in advancing the College of Sciences and Georgia Tech.”
As a novice assistant professor entering a classroom of 70 students for the first time, Collard says, “expertise in my thesis research did little to inform me about how to connect to students in the class.” Twenty-five years later, Collard’s journey in academic leadership continues as he strives to further elevate teaching and learning and to broaden participation in STEM research. “My aim is to make sure that students know I’ve got their backs,” he says. “If they fail, then I have failed.”
The office of M.G. Finn in the Molecular Science and Engineering Building blends chemistry and jazz. Amid an extensive library of science literature and textbooks is a large photograph of jazz musicians posing in 1950s Harlem. The black-and-white photo evokes creativity, innovation, and inspiration; it hangs directly across Finn’s desk and occupies a prominent space in his field of vision. The juxtaposition of keen intellectual pursuits against avid enthusiasm for improvisation reflects Finn’s approach to scientific leadership.
Finn’s resume is as impressive as it is long. His research spans far and wide within the fields of chemistry, biology, and materials science. A lifelong passion for science has blazed his trail to the Pediatric Technology Center (PTC) at Georgia Tech, where he recently became the first professor to hold the James A. Carlos Family Chair for Pediatric Technology. The newly endowed chair was made possible in part by the generosity of Georgia Tech alumnus James A. Carlos, the vice chairman of the Children’s Healthcare of Atlanta Foundation and one of many corporate and community leaders in Atlanta who are dedicated to improving pediatric medicine.
“I am truly honored. The chair comes with significant resources that aren’t tied to any particular project, allowing us to initiate and continue important research in pediatric medicine,” Finn says. “The chair also brings high-profile recognition to the work being done thanks to PTC,” adds Finn, who also chairs the School of Chemistry and Biochemistry.
LOFTY INTENTIONS
PTC is a research center established through a pediatric research alliance between Georgia Tech, Children’s Healthcare of Atlanta (CHOA), Emory Healthcare, and Morehouse School of Medicine. As PTC’s chief scientific officer, Finn orchestrates a vast pool of talent. Like the quintessential jazzman, Finn and his team bring together artists who, in ensemble, create innovative music that challenges the limits of conventional thinking. However, his “artists” are professionals in the healthcare and STEM fields, members of the Georgia Tech-CHOA-Emory community, and their “music” saves lives right here in Atlanta.
“Getting the right people in the same room is the hard part,” Finn says. “When you’ve gotten that far, that’s when the excitement really takes off.”
How exactly does PTC save lives? It starts with lofty intentions, such as the PTC’s goal to end child deaths in Georgia due to sickle cell anemia by 2025. Sickle cell anemia is only one of many diseases that originate from the mutation of a single gene. “Roughly 6,000 single-gene related diseases have been identified so far,” says Finn, “and these diseases can, in principle, be cured by a process called single-gene editing, whereby the offending gene is restored to its natural function.”
The molecular machinery that edits specific genes has already been developed; the current challenge lies in actually delivering it. Overcoming this challenge through research and testing is just one role PTC and Finn’s lab have assumed.
REVOLUTIONIZING PEDIATRIC MEDICINE
Under the leadership of a council comprising representatives of the partner organizations, PTC is developing technologies in the fields of smartphone medical apps, 3D printing, regenerative medicine, and pediatric medical devices, among others. Finn heads this council and draws from his experience as a research scientist to recommend the allocation of resources.
PTC initiatives that promise to revolutionize pediatric medical science excite Sherry N. Farrugia, PTC’s director of operations and one of Finn’s colleagues on the council. “Using stem cells to repair lethal arrhythmias in infant hearts, developing implants that will grow with a child, creating interactive 3D images of a patient’s heart to help surgeons determine the effects of a procedure before they ever step into the operating room—these are just a few of the projects happening through the PTC,” Farrugia says.
In the five years since the PTC’s inception, this intersection of medicine, science, and engineering has led to great strides in pediatric medicine. For this reason, Finn believes that PTC should aim to establish Atlanta as the international hub for groundbreaking pediatric medical technology innovations.
“The people and facilities in Atlanta make working with pharmaceutical companies a natural fit,” Finn says. “We are also uniquely suited to work with individuals and smaller organizations to bring their discoveries to market. The partnerships could be mutually beneficial; the strengths of one could bolster the weaknesses of the other.”
To researchers joining his lab, Finn likes to say, “Be fearless, and take risks that might seem a little crazy.” These are words a jazz instrumentalist might say to inspire fellow musicians to reach new levels of improvisation. The same words have guided Finn himself and keep him pushing the boundaries of his science.
Matt Barr
Science Communications Intern
College of Sciences
The College of Sciences warmly congratulates Wade Barnes for receiving the Joseph Mayo Pettit Distinguished Service Award, the highest award conferred by the Georgia Tech Alumni Association. An alumnus of the School of Biological Sciences (B.S. Biology 1971), Barnes is a founding partner and physician at North Florida OB/GYN Associates.
The award honors alumni who have provided outstanding support of the Institute and the Alumni Association throughout their lives and who have provided leadership in their chosen professions and local communities.
“Being a graduate of Georgia Tech has been a powerful force in my life,” Barnes says. “Giving back to ‘Mother Tech’ always feels great because of what I have received from Tech.”
Barnes is a member of the advisory boards of the College of Sciences and of the School of Biological Sciences.
“We are delighted by this well-deserved recognition of Wade,” College of Sciences Dean Paul M. Goldbart says. “We have been beneficiaries of Wade’s untiring support of his alma mater, especially in creating research opportunities for our undergraduate students, and we are privileged to have been associated with him for all these years.”
Barnes received the award at the Georgia Tech Alumni Association 2017 Gold & White Honors Gala, held on Jan. 26, 2017, at the Ritz-Carlton Buckhead, in Atlanta, Georgia.
For marine protected areas established to help coral reefs recover from overfishing, size really does seem to make a difference.
In a study that may sound a new alarm for endangered corals, researchers have found that small community-based marine protected areas may be especially vulnerable to attack by crown-of-thorns sea stars (Acanthaster species) that can devastate coral reefs. The findings, published this week in the journal PLOS ONE, don’t diminish the importance of protected areas, but point to a new threat that may emerge from the degraded areas that often surround healthy ecosystems.
“The marine protected areas that are enforced in the Fiji Islands are having a remarkable effect,” said Mark Hay, Regents Professor and Harry and Linda Teasley Chair in the School of Biological Sciences at the Georgia Institute of Technology. “The corals and fishes are recovering. But once these marine protected areas are successful, they attract the sea stars which can make the small marine protected areas victims of their own success.”
The research, conducted on marine protected areas in the Fiji Islands, was supported by the National Science Foundation, the National Institutes of Health and the Teasley Endowment at Georgia Tech. The findings conflict with earlier studies that showed diminished sea star threats in large-scale marine protected areas.
“Successful small marine protected areas are like oases in the desert that may attract the sea stars, which can move tens of meters per day from degraded areas into the more pristine areas,” said Cody Clements, a Georgia Tech graduate student who conducted the research. “One of the potential benefits of marine protected areas was supposed to be protection against these outbreaks, but that didn’t seem to be the case in the areas we studied.”
In the Fiji Islands and other areas of the tropical Pacific, many villages have established marine protected areas where the local residents don’t allow fishing. Protecting the fish helps control seaweeds that harm the coral, a foundation species whose presence helps ensure a healthy ecosystem. Enforcing the ban on fishing depends on community support for protecting the reefs, which are part of the local culture – and can provide economic benefits through tourism and spillover of fish to the areas where harvest is allowed.
The impact of the restored reefs goes beyond the recovered areas, which can contribute coral and fish larvae to help repopulate nearby areas.
These sea stars are natural predators that attack coral by climbing onto reefs and turning their stomachs inside out to digest the coral. Large populations of sea stars can rapidly degrade reefs, consuming healthy coral and causing large-scale coral decline in a matter of weeks.
To determine the extent of the problem and learn if the sea stars indeed preferred marine protected areas, Clements studied reefs within and immediately surrounding three marine protected areas on the Coral Coast of the Fiji Islands. First, he conducted a survey to determine population densities of the predators on both protected reefs and fished reefs outside their borders.
The protected areas, Clements found, had as many as 3.4 times as many of the pests as the fished areas, and their densities were high enough to be considered Acanthaster sea star outbreaks.
Next, he tagged 40 sea stars and caged 20 on the eastern and 20 on the western borders of each protected area for two days before releasing them. Clements tracked each sea star, recording whether they had entered the protected or fished areas, and how far they moved into each. Nearly three-quarters of the sea stars entered the marine protected areas rather than the fished areas.
“There seems to be something that is attracting them to the protected areas,” said Clements. “They are picking up on something, but we don’t necessarily know what it is.” The research did not examine chemical cues that may be attracting the sea stars, though other studies have suggested the scent of corals being consumed may draw the crown-of-thorns.
Hay theorizes that the degraded coral reefs may protect the juvenile sea stars, which often hide by day until they reach a certain size. Adult sea stars have poisonous spines to protect them against fish or other potential enemies. Once they reach a certain size, they may move into areas with higher coral density.
Though the small size of the Fijian protected areas – averaging less than a square kilometer – may be a negative for protecting against the sea stars, they could be a positive in efforts to control the pest. Teams of local residents could capture the predators in periodic harvests to keep populations at lower densities, Hay said.
The animals can hide in the reefs, but their feeding habits usually make them visible. “Once you deal with them enough, you don’t have to see them to know where they are,” said Clements. “You can follow the feeding scars they leave on the coral. Where the scar ends, you know you’ll find one nearby.”
The sea stars are a natural part of the tropical Pacific environment, and outbreaks have been known for years. But there is concern that the densities of the pests and number of outbreaks have been increasing at a time when the coral reefs are more vulnerable.
“Reefs are facing many novel stressors today,” said Clements. “They might have been able to tolerate crown-of-thorns attacks in the past that are too much for them now. There are multiple threats facing coral reef ecosystems, and this doesn’t help.”
Coral conservation efforts can require a decade to show results, and Hay hopes the latest threat will not discourage designation of marine protected areas.
“Our findings do not negate the value of the protected areas, but raise an issue of concern to the people who manage them,” he said. “This looks like a threat that could be accelerating, and we wanted to raise the awareness.”
This research was supported by the National Science Foundation under grant OCE- 0929119, by the National Institutes of Health ICBG grant U19TW007401, and the Teasley Endowment to the Georgia Institute of Technology. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation or the National Institutes of Health.
CITATION: Cody S. Clements, Mark E. Hay, “Size matters: Predator Outbreaks Threaten Foundation Species in Small Marine Protected Areas,” (PLOS One, 2017). http://dx.doi.org/10.1371/journal.pone.0171569
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The enemies were thrown together, so the killing began.
Brandishing harpoon-like appendages covered in poison, two armies of cholera bacteria stabbed each other, rupturing victims like water balloons. Scientists at the Georgia Institute of Technology tracked the battle over sustenance and turf mathematically to gain insights that could, someday, lead to new, targeted therapies to fight infections.
But dueling bacteria would not be the infectors in that scenario; they’d be the remedy.
Conceivably, specially engineered assassin bacteria friendly to humans could kill harmful bacteria while sparing hordes of microbes that keep people healthy. By contrast, the antibiotics we use today vanquish harmful and helpful bacteria alike.
“If you could target harmful bacteria in the human gut, you could use engineered bacteria as a living antibiotic,” said Brian Hammer, an associate professor at Georgia Tech’s School of Biological Sciences. He cautioned, “We’re not anywhere near that right now.”
Calculating bacteria
But to harness bacteria for use in medicine or industry, or just to better understand how they thrive and spread, it’s helpful to determine the consistency of their actions over time. That’s where the math comes in.
Georgia Tech researchers applied to the bacteria existing physics equations developed to precisely describe the interactions of atoms and molecules. They found that those calculations could also precisely predict that two cholera armies would separate from each other into phases, like oil and water, when they met on the battlefield.
“The models predicted pretty much exactly when the phase separation would occur, and then we observed it happening just like the math said it would,” Hammer said. The predictive models were based what's called a “Model A” equation.
"Empirically, it's been used to describe metals that undergo phase separation,” Hammer said. “The type of curve we observed describing our results had never been used to describe living systems before.”
Hammer and Georgia Tech biologists Will Ratcliff, an assistant professor, and Samuel Brown, an associate professor, teamed up with Peter Yunker, an assistant professor in Georgia Tech’s School of Physics for the research. They published their results in the journal Nature Communications on Monday, February 6, 2017.
First authors were Hammer’s former graduate student biologist Eryn Bernardy, and Brown’s former postdoctoral assistant Luke McNally. Their research was funded by the National Science Foundation, the NASA Exobiology program, the Gordon and Betty Moore Foundation, the Wellcome Trust and the Human Frontier Science Program.
Rotting crab shells
Cholera bacteria are commonly found in water attached with other microbes to the shells of crabs and tiny krill, and people who drink that water can die within hours due to the severe vomiting and diarrhea the germs cause. The impetus for doing math on dueling cholera came from how they wage turf war on crab shells, which contain a material called chitin that switches on the harpoon function in Vibrio cholerae. No chitin, no stabbing.
“I was studying this amazing biological system,” Hammer said, “and I was looking for a way to visualize it.” Ratcliff and Yunker had been applying microscopy and mathematics to study the dynamics of yeast evolution and suggested Hammer give the method a try.
But before getting to the math itself, it’s important to understand a few things about Vibrio cholerae. First of all, most microbiologists think cholera bacteria use the harpoons to kill competing bacteria and not to destroy human cells.
The poisonous weapon is called a Type VI secretion system (T6SS), and is common. “This harpoon system is in about one quarter of Gram-negative bacteria,” Hammer said. “So, this bacterial dueling is going on all around you.”
Gram-negative bacteria have thinner walls, which can be punctured more easily. Gram-positive bacteria have thicker walls less susceptible to the harpoons, and human cells may be even more difficult to penetrate.
And the stabbing mechanism is not limited to pathogens like cholera. Many harmless bacteria use it, too. But more is known about the mechanism in pathogens, because harmful bacteria are more often the focus of scientific study than harmless bacteria, Hammer said.
Armed and generous
Harpooning cholera stab randomly at all bacteria they come into contact with, including each other, but Vibrio cholerae of the same strain are immune to each other’s stabs. So, they kill their enemies but not their own kind.
The killing also appears to go hand in hand with cooperative social behavior. The researchers found that bacteria that are good at killing together are also good at sharing with each other and building a community.
It starts with creating a common pool of food. “Bacteria do a lot of their digestion outside their cells,” Hammer said. But having all that food lying around is risky.
“You need a strategy for ensuring that all the effort of chewing up and digesting food benefits you and your relatives, and not someone else who comes and plunders it.” When a strain of bacteria kills invaders, it preserves the fruits of its labor, and multiplies, passing on its genes.
Brown’s postdoctoral researcher Luke McNally examined the genomes of many types of bacteria (in addition to cholera) that use poison harpoons. Some strains had six or seven harpoons, and some harpoons had multiple poisons. And there appeared to be a correlation between weapons and cooperation.
“We found that the more weaponry a bacteria strain had in its genome, the more it looked like it was apt to share,” Hammer said.
Purple, red, blue
Under the microscope, the battling bacteria strains actually did look a little like beads of oil and water separating out on a flat surface. They were stained two different colors like red and blue, so they could be told apart.
“We start with two strains well mixed,” Hammer said. “We jokingly call this the salad dressing model, because you shake oil and water, and they’re well mixed, and you let it sit, and they phase separate.”
When they’re well mixed, the two strains of cholera appear as one purple mass, but as they kill each other and conquer separate territories, they divide into red blotches and blue blotches.
There are significant differences between how chemical and living systems operate. For example, the bacteria also reproduce and multiply; molecules don’t. But the basic math that worked for materials also worked for the bacteria.
Future applications?
“In your gut, a lot of useful bacteria are Gram-positive,” Hammer said. “But there might be a small number of Gram-negative bacteria messing up your gut community, and perhaps engineered bacteria with spears could get rid of just those Gram-negative.”
Also, an external material like chitin, which switches the harpoon function on in cholera bacteria, could be given along with assassin bacteria to trigger their weaponry, and then deactivate it when the chitin is gone.
Arben Kalziqi and Jennifer Pentz, and Jacob Thomas all of Georgia Tech, also co-authored the research paper. The work was funded by the National Science Foundation (grants DEB-1456652, MCB-1149925), the NASA Exobiology program (grant NNX15AR33G), the Gordon and Betty Moore Foundation (grant 4308.07), the Wellcome Trust (grant WT095831) and the Human Frontier Science Program (grant RGP0011/2014). Findings and opinions are those of the authors and do not necessarily reflect the official views of the funding agencies.
Historically speaking, women have been underrepresented in professions heavy in science technology, engineering, and mathematics (the STEM fields). You wouldn’t know it to look at the 2017 class of Petit Undergraduate Research Scholars.
This year’s class – tied for the largest number of students, 22, with last year’s class – features 16 women, a record number in the program’s 18-year history.
Since it was established as a summer research experience in 2000, the program has supported hundreds of top undergraduate researchers who have moved on to successful careers in research, medicine, and industry. But it has never supported this many women at one time. That first year, six of the seven scholars were men.
Oh, how times have changed.
“It’s empowering to be surrounded by motivated women who aren’t going to stop moving forward in STEM just because the field has been traditionally male dominated,” says Madeline Smerchansky, a third-year student in the Wallace H. Coulter Department of Biomedical Engineering, who has been doing undergraduate research for about a year.
“But I’m excited about the Petit Scholars program because of how independent it will allow me to be in the lab,” she adds. “I think it will help me solidify my post-graduation plans while providing valuable experience and networking in the research world.”
The Petit Scholars program, open to all Atlanta area university students, basically gives scholars room to breathe intellectually. What makes the program unique is that it provides for a full year of research in state-of-the-art labs of the Parker H. Petit Institute for Bioengineering and Bioscience.
“The scholars will work alongside graduate students or postdoctoral mentors in labs across the spectrum of bioengineering and bioscience,” explains Raquel Lieberman, the Petit Institute researcher who serves as faculty mentor for the program.
“The sustained research effort over the course of a year will enable the Petit Scholars to contribute to a research project in a substantive way,” adds Lieberman, an associate professor in the School of Chemistry and Biochemistry.
This year’s group of students come from three different universities (while most come from Georgia Tech, two students are from Morehouse and one is from Agnes Scott).
They represent nine different majors, reflecting the multi-disciplinary approach the Petit Institute takes toward research. The largest group (six students) is majoring in biomedical engineering (BME) in the Coulter Department.
“I’ve been interested in becoming a biomedical engineer since I was a sophomore in high school and my math teacher brought in real data from a hospital for us to work on,” says Isabelle Stasenko, one of the BME undergrads. “I loved the idea of doing the math and research behind the medicine, and I still do.”
Stasenko figures the the program will help confirm if a career in research is the right path for her. In the meantime, the Petit Scholar experience is a source of empowerment for her.
“It’s exciting to have so many powerful women pursuing and excelling in engineering fields,” she says. “Georgia Tech was originally an all-boys institution, so to see the number of women growing like this is amazing.”
Another BME undergrad, Rebecca Keate, says she knows a rare opportunity when she sees one: "As a second-year undergraduate, I recognize that a lot of students are not granted the same opportunities as I am, to have such a sophisticated research experience at a powerhouse like Georgia Tech."
But she admits to being tired of hearing that she, as a woman, is, “prone to be less successful in any STEM program. I disagree with this opinion. I refuse to believe that my intelligence is any less than a man’s. And as an engineer, I hope to be held to the highest standards, regardless of being a woman.”
Here they are, the 2017 Petit Scholars (plus, their school, their mentor, and the Petit Institute researcher’s lab they’ll be spending the year in):
• Ashley Alexander (Georgia Tech, Dong-Dong Yang, Frank Rosenzweig)
• Cedric Bowe (Morehouse, Vineet Tiruvadi, Rob Butera)
• Mi Hyun Choi (Georgia Tech, Joshua Lee, Frank Hammond)
• Hassan Fakhoury (Georgia Tech, Quoc Mac, Gabe Kwong)
• Sarah Ghalayini (Georgia Tech, Moustafa Ali, Mostafa El-Sayed)
• Daniel Gurevich (Georgia Tech, Ilija Uzelac, Flavio Fenton)
• Connor Huddleston (Georgia Tech, Zhenglun “Alan” Wei, Ajit Yoganathan)
• Rebecca Keate (Georgia Tech, Shlomi Cohen, Jennifer Curtis)
• Siyi “Sophie” Li (Georgia Tech, Aline Yonesawa, Mike Davis)
• Amelia Matthews (Georgia Tech, Sam Tonddast-Navaei, Jeff Skolnick)
• Esperance Mugabekazi (Agnes Scott, Sang-Eon Park, Robert Gross)
• Michelle Myrick (Georgia Tech, Inseung Kang, Aaron Young)
• Franck Nijimbere (Morehouse, Bo Broadwater, Harold Kim)
• Chiagoziem “Chichi” Obi (Georgia Tech, Udita Brahmachari, Bridgette Barry)
• Renee Puvvada (Georgia Tech, Katily Ramirez/Michael Bellavia*, Todd Sulchek)
• Celeste Runnels (Georgia Tech, Nicholas Kovacs, Loren Williams)
• Arushi Saini (Georgia Tech, Osiris Martinez-Guzman, Amit Reddi)
• Amanda Schaefer (Georgia Tech, Emily Jackson, Hang Lu)
• Madeline Smerchansky (Georgia Tech, Kirsten Parratt, Krishnendu Roy)
• Isabelle Stasenko (Georgia Tech, Efraín Cermeno, Andrés García)
• Moya Tomlin (Georgia Tech, Dustin Huard, Raquel Lieberman)
• Corey Zheng (Georgia Tech, Seung Yup “Paul” Lee, Erin Buckley)
LINKS:
Petit Undergraduate Research Scholars
CONTACT:
Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience
When Alfred H. Merrill launched his career as an assistant professor at Emory University in 1981, he wanted to carve out his own unique niche, to do something that would distinguish himself while contributing to the growing body of research in biochemistry and molecular biology. So, he jumped into an enigma.
Merrill, a professor in the School of Biology in the College of Sciences and Smithgall Institute Chair of Molecular Cell Biology at the Georgia Institute of Technology, became a pioneering researcher in the field of sphingolipids (named “sphingo,” for “sphinx,” because sphingolipids are considered as enigmatic as the Great Sphinx).
Now, 30 years later, his early work is being recognized as some of the most influential research of its kind – classic stuff, literally.
“Right off the bat, my lab had the good luck to find that the textbook pathway for biosynthesis of sphingolipids was wrong,” says Merrill.
Niche carved, first contribution made.
Then came the bigger surprise: that sphingolipids are involved in cell signaling. This came through an exciting collaboration that resulted in publication of three back-to-back papers in 1986 that have just been designated as “Classics” by The Journal of Biological Chemistry (JBC). The Classics are selected from articles that have previously appeared in the JBC (since its founding in 1905), and considered particularly impactful. They’re reprinted in their original form, along with an explanation of the research’s groundbreaking contribution to science.
“The JBC is considered one of the most prestigious journals in basic biochemistry, so for one’s work to be selected as a ‘Classic’ is a real honor,” says Merrill, a researcher in the Petit Institute for Bioengineering and Bioscience, who finds himself in some elite company, as the Classics series includes papers by many of the all-time legends in biological chemistry.
“In some cases, such as ours,” he adds, “the specifics of the papers are probably not as important as that they turned people’s minds around and got them to look at a field from a different angle.” The JBC Classics entry calls out the research’s impact right there in the headline: “Solving the Riddle of the Role of Sphingolipids in Cell Signaling.”
Merrill likes to emphasize that these findings were the synthesis of ideas and expertise from many scientists, not just one investigator. It started with his former post-doctoral mentor, Robert M. Bell at Duke University.
“In Dr. Bell’s lab, the major focus was glycerolipid metabolism, but he had become intrigued that diacylglycerols were being claimed to be signaling molecules that activate protein kinase C (PKC),” Merrill says. “Skeptical of the idea at first, Yusuf Hannun and others in his lab developed sophisticated ways to study PKC and they not only became leading experts in how lipids activate this kinase but also happened to notice that a sphingolipid, sphingosine, could inhibit it.”
This was the underpinning of the first of the three papers, entitled, “Sphingosine inhibition of protein kinase C activity and of phorbol dibutyrate binding in vitro and in human platelets.”
“Since these were compounds that my lab had been studying, we became heavily involved,” says Merrill, whose only other co-author for all three papers was Bell. Hannun co-authored two of the papers.
“But as the project became even more sophisticated, additional collaborators were needed,” Merrill adds.
Two were other faculty at Emory, Dr. Jack Kinkade for the paper entitled, “Inhibition of phorbol ester-dependent differentiation of human promyelocytic leukemic (HL-60) cells by sphinganine and other long-chain bases,” and Dr. J. David Lambeth for the third paper, “Inhibition of the oxidative burst in human neutrophils by sphingoid long-chain bases. Role of protein kinase C in activation of the burst.”
According to George Carman, director of Rutgers University’s Center for Lipid Research (and the JBC associate editor who nominated the trilogy for Classic status), the papers “showed that a lipid backbone of sphingolipids could affect a cell signaling pathway (Protein Kinase C) at not only by inhibiting the in vitro activity but also by affecting diverse cell functions dependent on protein kinase C (platelet activation, the neutrophil respiratory burst and cell differentiation). This work started a whole sub discipline of lipid signaling that affects cell physiology.”
Before these papers, according to Merrill, there was no clear understanding of why sphingolipids were built upon the sphingosine backbone, which differs from all other lipid categories. The research demonstrated that sphingosine is a highly bioactive molecule capable of altering cell signaling and a wide spectrum of cell functions.
"Once the papers stimulated scientists to think about sphingolipids from that perspective, additional bioactive metabolites were discovered and characterized, resulting in a now very large field of cellular regulation by sphingolipid mediators,” Merrill says. “This, in turn, led to discoveries about how defects in these pathways result in disease and new strategies to prevent and treat disease.”
Almost everything that Merrill’s lab has subsequently discovered has been built on this new perspective on sphingolipids, and involved some sort of collaboration: The connection of sphingolipids with diseases caused by the fumonisin mycotoxins, in collaboration with Ron Riley at the USDA; that dietary sphingolipids suppress colon cancer with Dirck Dillehay, and development of drug leads based on sphingolipids with Dennis Liotta (both at Emory); development of mass spectrometric methods to quantify all of the known bioactive sphingolipids and discover new ones, with Cameron Sullards, director of the Georgia Tech Department of Chemistry and Biochemistry Mass Spectrometry Center; characterization of the mammalian genes and enzymes that make ceramides, with Tony Futerman at the Weizmann Institute; changes in sphingolipid metabolism in ovarian cancer, with John McDonald (Petit Institute); and so on.
With the assistance of research technician Samuel Kelly, Merrill has returned to working fulltime in the lab, to develop new ways to study sphingolipid structure and function. Thinking back over his career, Merrill is proudest of the approach his lab and collaborators have taken in their research, rather than any one specific finding.
“We have expended a lot of effort to develop better methods to analyze sphingolipids and model systems to study them more definitively,” he says. “This has often been slow and sometimes tedious, but it has resulted in solid data that have stood the test of time, and in many unexpected discoveries.”
LINKS:
The Journal of Biological Chemistry "Classics"
CONTACT:
Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience
Four faculty in the College of Sciences, one in the Scheller College of Business, and one in the Ivan Allen College of Liberal Arts have been named fellows of the American Association for the Advancement of Science for 2015. Fellows are elected by their peers in recognition of distinguished contributions to science or its application.
Those recognized include:
- School of Biology Professor Yury Chernoff: For distinguished contributions to the field of molecular/cellular biology, particularly for understanding prion formation and deciphering the chaperone role in prion propagation in yeast.
- School of Chemistry and Biochemistry Professor Christoph J. Fahrni: For distinguished contributions on the development of metal ion sensors and for discoveries on the mechanisms for metal transport and storage during growth and development.
- School of Earth and Atmospheric Sciences Professor Jean Lynch-Stieglitz: For bringing physical oceanography approaches to the study of transient circulation changes during ice ages, providing a window into the ocean’s interaction with today’s climate change.
- School of Public Policy Professor Philip Shapira: For distinguished contributions to science, technology and innovation policy, particularly for contributions to improved understanding of effective means of modernizing manufacturing.
- Scheller College of Business Regents Professor Marie Thursby: For research contributions to the role universities play in innovation and the development of pioneering graduate programs that prepare students for careers commercializing new technologies.
- School of Chemistry and Biochemistry Professor Emeritus Paul H. Wine: For distinguished contributions to the fields of physical and atmospheric chemistry, particularly for experimental studies of the kinetics and mechanisms of fast free radical reactions.
A formal ceremony to induct new fellows will be held during the AAAS Annual Meeting in February.
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