March 2, 2017 | Atlanta, GA

Though tailpipe emissions could fall in the years ahead as more zero-emission vehicles hit the streets, one major source of highway air pollution shows no signs of abating: brake and tire dust.

Metals from brakes and other automotive systems are emitted into the air as fine particles, lingering over busy roadways. Now, researchers at Georgia Institute of Technology have shown how that cloud of tiny metal particles could wreak havoc on respiratory health.

In a study published January 31 in the journal Environmental Science & Technology, the researchers described how vehicle-emitted metals such as copper, iron and manganese interact with acidic sulfate-rich particles already in the air to produce a toxic aerosol.

“There’s a chain reaction happening in the air above busy highways,” said Rodney Weber, a professor in Georgia Tech’s School of Earth & Atmospheric Sciences. “Acidic sulfate in the atmosphere comes into contact with those metals emitted from traffic and changes their solubility, making them more likely to cause oxidative stress when inhaled.”

The study, which was sponsored by the National Science Foundation and the U.S. Environmental Protection Agency, showed how the metals are emitted mainly in an insoluble form but slowly become soluble after mixing with sulfate.

“Sulfate has long been associated with adverse health impacts,” said Athanasios Nenes, a professor and Georgia Power Scholar in the School of Earth & Atmospheric Sciences and the School of Chemical & Biomolecular Engineering. “The old hypothesis was that the acidic sulfate burns your lung lining, which in turn leads the bad health effects. But there is not enough acid in the air alone to really have that impact.”

But sulfate plays a key role in making metals soluble before they are inhaled, which could explain the association of sulfate with adverse health impacts, the researchers said.

The researchers collected samples of ambient particulate matter in two locations in Atlanta – one near a major interstate highway and another urban site 420 meters away from the roadway. They analyzed the chemical content, size distribution and acidity of the samples.

A significant amount of the ambient sulfate found was similar in size to the metal particles, suggesting that the ambient sulfate and metals were mixed within individual particles, which over hours or days would allow the acidic sulfate to convert the metal into a soluble form.

To quantify just how dangerous the aerosol could be, the researchers developed a high throughput analytical system for a chemical assay – called oxidative potential – that simulates the toxic response that such a mix would have on cellular organisms. This instrument was used to generate large data sets on ambient aerosol oxidative potential, which when utilized in an earlier epidemiological study, researchers at Georgia Tech and Emory University found that the chemical assay was statistically associated with hospital admissions in Atlanta for asthma and wheezing.

In the new study, the researchers observed that the peak toxicity indicated by the assay was closely correlated to those particles that contained the largest amount of soluble metals, which occurred only when metallic particles mixed with highly acidic sulfate.

“That’s the smoking gun,” Nenes said. “The sulfate essentially dissolves those metals; when you breathe in those particles, the metals could be absorbed directly into the blood stream and cause problems throughout the body. For the first time, a mechanism emerges to explain why small amounts of acidic sulfate can adversely affect health.”

While the sample taken from the testing site located farther away from the highway had less particulate metal, there was still enough to cause an increase in the oxidative potential, showing that roadway pollution could travel through the air and potentially cause problems in surrounding areas as well.

Dust from brakes and tires isn’t the only source of metals in the air. Incinerators and other forms of combustion also produce mineral dust and metallic particles, which could mix with sulfate to trigger a similar reaction.

The researchers noted that while the amount of particulate sulfate in the southeastern United States has decreased during the past 15 years as sulfur dioxide emissions from power plants have fallen, there’s still enough acidic sulfate in the air to keep the pH of particles very low, in the range of 0 to 2, transforming insoluble ambient metals to a soluble form.

“Vehicle tailpipe emissions are going down, but these kinds of emissions from braking will remain to some extent, even if you drive an electric car,” Weber said. “Therefore, this kind of process will continue to play out in the future and will be an important consideration when we look at the health effects of particulate matter.”

This material is based upon work supported by the National Science Foundation under Grant No. 1360730 and the U.S. Environmental Protection Agency under Grant No. RD834799. 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 U.S. Environmental Protection Agency.

CITATION: Ting Fang, Hongyu Guo, Linghan Zeng, Vishal Verma, Athanasios Nenes and Rodney J. Weber, “Highly acidic ambient particles, soluble metals and oxidative potential: A link between sulfate and aerosol toxicity,” (Environmental Science & Technology, 2017). http://dx.doi.org/10.1021/acs.est.6b06151.

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Josh Brown
Research News
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March 1, 2017 | Atlanta, GA

Researchers have successfully identified biological signatures in pediatric patients with newly diagnosed Crohn’s disease (CD) capable of predicting whether a child will develop disease-related complications requiring major surgery within three to five years. The results of this research, “Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study,” have been published in the journal, The Lancet. 

This groundbreaking work is the result of the Crohn’s & Colitis Foundation’s “RISK Stratification” study, the largest new-onset study completed on pediatric Crohn’s disease patients. It is a multicenter research initiative that consists of 25 U.S. institutions and three from Canada and a cohort of 1,112 CD children enrolled at diagnosis, of which 913 were included in the published study. Of the 28 research sites, four are located in Atlanta - Emory University, Georgia Institute of Technology, Children’s Healthcare of Atlanta, and the Children’s Center for Digestive Health Care. The goal of this research was to identify measurable indicators of the two most common complications in pediatric Crohn’s disease that require surgery - stricturing and penetrating disease. 

Stricturing, also referred to as fibrostenosis, is characterized by a build-up of fibrotic scar tissue which leads to thickening of the intestinal wall and narrowing of the intestinal passage. Penetrating disease is the result of sustained inflammation that spreads beyond the intestinal wall resulting in the creation of fistulas, abnormal connections between the intestine and other organs. Penetrating complications can also lead to the formation of abscesses at the sites of fistulas. 

“Twenty five percent of patients with Crohn’s disease account for 80 percent of complications, hospitalizations, surgery and health care costs. The aim of RISK is to preemptively identify those 25 percent of patients at diagnosis,” Subra Kugathasan, M.D., Emory University, principal investigator and lead author of the paper. “Through the study of baseline gene expression, immune reactivity, and intestinal bacteria, we have identified distinct biological signatures capable of predicting stricturing and penetrating disease, at diagnosis. After analyzing millions of biological and clinical data points, RISK has generated a composite risk stratification model.” 

"Stricturing and penetrating disease account for substantial morbidity in both pediatric and adult patients with Crohn’s disease, but there are no validated models to predict risk and the effect of treatment," said Caren Heller, M.D., chief scientific officer of the Foundation. 

RISK study researchers looked at intestinal gene expression levels to identify risk factor genes whose levels are altered (increased or decreased) at enrollment, and identified distinct biological gene expression signatures at baseline that could distinguish children who will develop strictures form those who develop fistulas or abscesses, without the confounding effects of treatment on gene expression. Therefore, these genetic signatures together with other biological and clinical variables they evaluated could be used as predictors of complications and treatment outcomes at diagnosis. 

"Importantly, the functional nature of these genetic signatures is consistent with the clinical presentation of the complications," said Ted Denson, M.D., Cincinnati Children's Hospital, co-principal investigator and lead author of the paper. "This means that while patients who develop fibrostenosis exhibit, at diagnosis, increased levels of several genes involved in the fibrosis process, patients who develop penetrating disease have increased levels of genes involved in the inflammatory response."

In addition to providing predictive biological signatures for development of complications, the RISK study also found that patients who receive early anti-TNFa biologic treatment, within three months of diagnosis, were less likely to develop penetrating complications. However, patients with stricturing complications were poorly responsive to early intervention with biologics. These data support the utility of risk stratification of pediatric Crohn’s disease patients at diagnosis, and may guide early tailored use of anti-TNFa therapy. The data also highlight the unmet medical need to find new treatment options for children likely to develop strictures. 

“These discoveries are great steps toward precision medicine in the treatment of pediatric Crohn's disease,” said Andrés Hurtado-Lorenzo, Ph.D., Director of Translational Research of the Foundation. “In the coming years, we plan to translate these findings into a risk diagnostic tool that could use these biological signatures as biomarkers to predict risk of complications and to help clinicians make therapeutic decisions at diagnosis.”

The Foundation has made significant investments in support of pediatric IBD research through the PRO-KIIDS network, an umbrella for clinics participating in pediatric IBD research. Although many projects are expected to arise from this network the Risk Stratification has been the flagship study.  

“Pediatric patients are the fastest growing group of the IBD population. Under the auspices of the PRO-KIIDS network, every major pediatric IBD center in the country is touched by our work or funding,” said Michael Osso, President and CEO of the Foundation. “Through the network, and the results of the RISK study, we are furthering research that will significantly lower the treatment burden on kids, and help minimize side effects on the quality of life surrounding the most vulnerable of patients.”

As part of the study, Georgia Tech postdoctoral researcher Urko Marigorta analyzed RNAseq gene expression data from biopsies provided by Cincinnati Children's Hospital. The work identified dozens of pathways that are differentially expressed in complicated disease, and showed that immune activity is more disrupted in penetrating disease while extracellular matrix is more involved in stricturing disease. Inclusion of these profiles in a statistical model with the serological and classical markers improved the predictive accuracy of the model significantly.  

“We performed statistical and bioinformatic analyses of the genomic data which led to enhanced discrimination of which patients are likely to progress to complicated disease,” said Greg Gibson, a professor in the Georgia Tech School of Biological Sciences and one of the paper’s co-authors. “The involvement of TNF-alpha signaling in progression to stricturing disease is consistent with the overall finding that these are the patients who respond to TNF-alpha therapy.”

This seminal work and its discovery represent over $10 million investment by the Crohn’s & Colitis Foundation, nearly 10 years of work, and collaborative team effort. Dr. Thomas Walters from the Hospital for Sick Kids, Canada shares lead authorship with Drs. Kugathasan and Denson. In addition, Dr. Jeffrey Hyams (Connecticut Children’s Medical Center), and Dr. Marla Dubinsky (Mount Sinai Hospital, New York) share authorship. 

About the RISK Stratification Study
The RISK Stratification Study enrolled 1,800 patients from 28 clinics, with a focus on 913 children with Crohn’s disease enrolled at diagnosis and complication-free following 90 days after diagnosis. This 36-month prospective inception cohort study included well documented clinical, demographic, and biological sample collection every six months on all patients for three years with continuing follow up for five years. 

About the Crohn's & Colitis Foundation 
The Crohn's & Colitis Foundation is the largest non-profit, voluntary, health organization dedicated to finding cures for inflammatory bowel diseases (IBD). The Foundation’s mission is to cure Crohn's disease and ulcerative colitis, and to improve the quality of life of children and adults who suffer from these diseases. The Foundation works to fulfill its mission by funding research; providing educational resources for patients and their families, medical professionals, and the public; and furnishing supportive services for those afflicted with IBD. For more information visit www.crohnscolitsfoundation.org. 

- Written by Crohn’s & Colitis Foundation

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The recently named Regents Professor combines imagination, courage, and optimism in his approach to origins-of-life research.

February 28, 2017 | Atlanta

Nicholas V. Hud imagines that life evolved from molecules that were the result of chemical reactions that took place at millions of locations, scattered across the landscape of early Earth, each location producing a type of molecule that could grow as chemistry permitted. As the molecules grew, they ‘crept’ across the land in puddles and rivulets, mixing with other sets of molecules. The molecular aggregates became more complex mixtures until, after eons of mingling, the transition from chemistry to biology occurred.

The television show “Star Trek: The Next Generation” has alluded to this scenario. In the series finale, the omnipotent antagonist Q takes the hero, Captain Jean-Luc Picard, back in time to early Earth: a barren wasteland except for small pools of water stretching across the surface. As Picard examines a pool, Q mockingly tells him, “This is you. Right here, life is about to form on this planet for the very first time. Strange, isn’t it? Everything you know, your entire civilization, it all begins right here in this little pond of goo.”

“I thought the whole setting looked as I would imagine it,” says Hud, a professor in the School of Chemistry and Biochemistry.

In Hud, such imagination is coupled with ingenuity and creativity in breaking down large research objectives into smaller ones and attacking those one by one. This—plus a fearlessness in pushing new ideas and a cheery optimism—makes Hud an outstanding professor and scientist. For his achievements so far, the University System of Georgia (USG) last year named Hud a Regents Professor. This honor is the highest bestowed by USG for distinction and achievement in teaching and scholarly research.

Understanding how chemistry begat biology is one of the grand challenges of science. It is the focus of Hud’s research and of the Center for Chemical Evolution (CCE), which Hud directs. The CCE has positioned Georgia Tech as one of the leading institutions in origins-of-life research.

Hud was a graduate student when origins-of-life research was undergoing a renaissance in the early 1990s. “It made me wonder: where did these molecules come from?” says Hud, referring to the biological polymers—RNA, DNA, and proteins—that are central to all the chemistry of life. How did the transition from single molecules to biological polymers occur?

“I had a feeling that it might be possible to address some parts of this problem,” Hud says. “We’ve made good progress within CCE, but we need to do more.”

OVERARCHING HYPOTHESIS

Origins-of-life research is vast in scope. Hud and CCE are focused on the origins of biopolymers. The origins of nucleic acids, which are DNA and RNA in current life, is a particularly challenging question. It starts with what has been named the “nucleoside problem.”

Unlike amino acids—the building blocks of proteins—which can be produced in relatively simple chemical reactions, nucleosides--the building blocks of nucleic acids—are trickier to make. Each nucleoside has a “base,” which is the pairing part of the molecule, and a sugar, which is ribose in RNA and deoxyribose in DNA. Although ribose and the bases of RNA can be made in model prebiotic reactions, Hud says, it has proven virtually impossible to connect the bases to ribose by reactions that would have likely happened on early Earth.

Instead of using the bases found in modern nucleic acids to figure out how nucleosides may have formed from primordial pools, Hud is looking for different bases that connect easily with a sugar to form a nucleoside.

“If you change just one or two atoms from the molecules that we have in life today, it may be possible to come up with molecules that will easily form RNA-like polymers,” Hud says. “That’s our overarching hypothesis: that life started with slightly different molecules and developed more sophisticated chemistry over time.”

Whether the question of how chemistry gave rise to biology will ever be fully answered, Hud says that CCE research will not only further our understanding of life’s origins, but also reap benefits in other ways. “We are finding reactions for the synthesis of molecules and polymers in water that rival the best of those designed by synthetic chemists,” Hud says. “If we are successful, these molecules and polymers could facilitate the production of useful materials and therapeutics, for example.”

A WACKY IDEA

Research on the nucleoside problem has led Hud to revitalize an old origins-of-life theory, one that counters the “RNA world” idea, which caught fire when Hud was a graduate student. Questioning RNA as the end-all be-all molecule of life, Hud prefers the idea of a series of pools and hotbeds of chemical activity spread over a wide area, all involved in different chemical reactions. In time, the separate pools engage in cross-talk, cooperating and evolving synchronously, until enough components coalesce into membrane-bound cells.

“I think early on there were many different molecules simultaneously making the transition from small molecules to polymers,” Hud says. He thinks of the system as “a giant, distributed organism where the chemistry that we have in cells today was operating over the surface of the land.” As chemistries were evolving in different parts of this “megaorganism,” the pools of chemical activities were sharing solutions to certain problems in the chemistry of what needed to be done to initiate life, Hud explains.

“I like this model of early life where in one place a solution arises that is able to catalyze a reaction that’s needed a kilometer away,” Hud explains. “Some people think this is a wacky idea,” Hud adds with a chuckle. But, he emphasizes, “the theory fits the current data well.”

AN OPTIMIST

“Thinking about the wonder and the power of chemistry to give rise to molecules as complex as what we have inside of us is exciting,” Hud says. The drive that moves him toward uncovering the mysteries of the eons also makes him optimistic. Unraveling the steps from chemistry to biology has become a consuming passion that permeates his speech and manner with cheerful positivity.

“Within a few years, we may be able to understand the chemistry that gives rise to life,” Hud says. “In doing that, chemists could use what we learn to make new materials, medicines, and therapeutics. As we understand more about the nature of the universe, I am hopeful that all of us will have a greater appreciation for the special role Earth played in the origins of life, which could result in us making better choices for the world and for society.”

Nathanael Levinson
Contributing Writer
College of Sciences

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A. Maureen Rouhi, Ph.D.
Director of Communications
College of Sciences

GTNeuro researchers on the cutting edge are exploring the frontier between our ears

February 27, 2017 | Atlanta, GA

Imagine trying to eavesdrop on the human brain, with its complex, chattering galaxy of 86 billion neurons, each one connected to thousands of other neurons, holding cellular conversations through more than 100 trillion synaptic connections.

It is a dense and noisy communication network, wrapped and hidden deep within precious tissue. We’ve pondered over, poked, and prodded the brain for centuries. But so much of what goes on inside our skulls is a mystery and neuro-research is still closer to the starting line than the finish.

At the Georgia Institute of Technology, scientists and engineers from different backgrounds have formed an interdisciplinary research community called ‘GTNeuro.’ They’re out to improve our understanding of the brain and the entire nervous system, and they’re seeking and creating the means to treat neurological diseases and injuries, even boost neural function, bringing the mysteries of the human brain into clearer focus.

“There’s a large and growing community here, of people focused on basic science, translation, and technology related to a range of neurological diseases and disorders, and all of this is bolstered by a vibrant educational and training environment,” says Garrett Stanley, a researcher in the Petit Institute for Bioengineering and Bioscience and professor in the Wallace H. Coulter Department of Biomedical Engineering (BME, a joint department of Emory and Georgia Tech).

 

Busy Intersection

Currently, there are more than 60 faculty researchers from Georgia Tech and Emory under the GTNeuro umbrella, and they come from the schools of Biological Sciences, Chemical and Biomolecular Engineering, Mechanical Engineering, Electrical & Computer Engineering (ECE), Psychology, and Physics at Georgia Tech, in addition to BME and multiple departments and divisions at Emory.

“The activities at Georgia Tech represent an intersection of basic neuroscience, and engineering-driven neuro-technology, a synergy which is necessary to drive the field forward,” says Stanley, who co-chairs the faculty steering committee for GTNeuro (with Petit Institute researcher Todd Streelman, professor and chair in the School of Biological Sciences).

“GTNeuro is just a very organic, faculty-driven kind of thing,” says Stanley, who also co-chairs the Neural Engineering Center (one of the research centers based at the Petit Institute, which also houses the Neuro Design Suite, a core lab facility) with Lena Ting, a professor who joined the Coulter Department 15 years ago.

“We were a small but tightly integrated group in the Laboratory for Neuroengineering, which occupied the third floor of the Whikater Building,” says Ting.

The small neuro-community of six neuro-researchers (two ECE faculty members, and four from BME) included, in addition to Ting, current Petit Institute researchers Rob Butera and Michelle LaPlaca.

“We pooled resources and had an internal seminar series, shared a lab manager. It was a very tight knit community,” says Ting. “Back then, we were about the only neuroscience research on the Georgia Tech campus. Slowly, over the last 12 years or so, that has changed dramatically.”

The burgeoning interest in neuro-research (across disciplines and department boundaries) was exemplified recently in the 25th edition of the Suddath Symposium at the Petit Institute (Feb. 21-22). The focus was neuroscience. Thought leaders from across the country and overseas spent two days discussing their research at the symposium, where the theme was “Neuromodulation and Synaptic Control: Modern Tools and Applications.”

 

Accelerating Progress

Every Monday in the Engineered Biosystems Building (EBB), a packed room takes in the GTNeuro Seminar Series, in which a wide range of experts – from Georgia Tech, Emory, and beyond – present cutting edge research.

These popular seminars, which start at 11 a.m. in EBB Room 1005, are video-conferenced to Emory, and recorded (and made available through the Georgia Tech Library).

Recent speakers have come from Case Western, Princeton, Harvard, in addition to brain experts from right here. Most recently, Audrey Duarte from Georgia Tech’s School of Psychology presented a talk entitled, “What can neuroimaging tell us about age-related memory changes?” In two weeks, Mark Frye from UCLA will discuss how flies see the world. And later in March, Machelle Pardue of the Coulter Department will talk about how to improve detection and treatment of diabetic retinopathy.

“We’re attracting 80, 100 people on a weekly basis,” says Ting, who is based at Emory, where she now heads up the Neuromechanics Lab. “That really suggests that no matter what kind of topic we’re presenting, and it’s been diverse, people are hungry to learn about neuroscience.”

Modern neuroscience is about a century old, but research has really hastened over the past 20 years, mostly due to the development of new tools and technology, according to Stanley. 

“Neuroscience has always pivoted around advances in techniques and technologies that enable us to better measure and manipulate different aspects of the networks of the tens of billions of neurons in the brain and the rest of the nervous system," he says.

Also, federal government support through programs like the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative are helping to drive research, “accelerating our understanding of both normal brain function, and function related to a range of neurological disorders,” says Stanley, whose own research is all about making sense of what all of those neurons are saying to each other.

 

Exploring the Network

The researchers who form GTNeuro are approaching the problem of understanding the brain and the nervous system from many directions with a diverse toolbox.

Ting’s work, for example, draws from neuroscience, biomechanics, rehabilitation, robotics, and physiology, which has led to discoveries of new principles of human movement. Her research is used by other researchers across the planet, to understand both normal and impaired movement control in humans and animals, and to develop better robotic devices.

Meanwhile, the lab of Petit Institute researcher Craig Forest is perfecting a robotic cleaning technique to automate and improve neuroscience research, and looking for ways to record what’s happening deep inside the brain.

“Our mission is to develop the tools that make new science possible,” says Forest, associate professor in the Woodruff School of Mechanical Engineering.

His lab developed a technique that will allow the pipettes used in patch-clamping to be reused over and over again. Patch-camping, the method used to stimulate and record neuron activity, involves touching the cell membrane with a glass pipette – a painstaking, prolonged process, and these pipettes are typically used only once.

The new cleaning process, integrated with the Autopatcher (robotic patch-clamping technology from the Forest lab), saves money on pipettes while gathering more data, faster.

The lab of Hang Lu, Petit Institute researcher and professor in the School of Chemical and Biomolecular Engineering, also is in the business of gathering large-scale data, through engineering BioMEMS (Bio Miro-Electro-Mechanical Systems) and microfluidic devices. These ‘Lab-on-a-chip’ tools are used to study how the nervous system develops and functions, and how genes and environment influence behavior.

“We’re a little different in terms of the space we occupy in neuro-research on campus,” says Lu, who was co-director with Stanley of the neuro-focused Suddath Symposium. “Functional researchers like Garrett or Rob Butera are very much down to the neurons and circuits. My lab’s approach is complementary.”

Butera (who holds a joint appointment in BME and ECE) and his lab colleagues have developed an implanted device that stimulates the vagus nerve to treat chronic inflammation, while also targeting and inhibiting unwanted nerve activity.

 

High Aspirations

Butera was principal investigator of the vagus nerve study, but the lead researcher was grad student Yogi Patel, who represents the next generation of neuroengineering.

“We’re actually working with a clinician at Emory to try and push this into some human evaluation,” says Patel, a fifth-year Ph.D. student. “That’s the key thing, to get this approved so it can be used in patients. It’s very promising.”

So is his future in neuroscience research. He already has a postdoctoral position lined up at Johns Hopkins University.

“It’s a fundamental neuroscience lab, more science than engineering,” says Patel, who is also serving as a consultant to industry on the side. “Long term, I still want to have my own research lab one day.”

It’s an aspiration that became a reality for Annabelle Singer less than a year ago, when she joined the Coulter Department at Georgia Tech and Emory, where her lab is exploring how neural activity guides behavior in health and disease. She was a lead author of recently published research demonstrating a non-invasive, flickering light treatment that reduces the build-up of plaques closely associated with Alzheimer’s disease.

This radically different approach has lots of promise, she says, but like so much else in a relatively nascent field like neuroscience, there are flights of steps to go before it can be translated into therapeutics for humans. Singer believes she’s in the right place to take those steps.

“There’s a culture of collaboration here, a kind of unity of purpose,” says Singer, who also recently joined the Petit Institute. “That was a big appeal for me.”

So was Emory’s Alzheimer’s Disease Research Center, and the Neuro Design Suite at the Petit institute, and the complementary research of colleagues who are all trying to make better sense of the brain, like Stanley, who wants to read and write the neural code.

“Patterns of activity in the brain are a language of sorts, but a language we don’t yet understand,” he says.

It only weighs about 3.3 pounds, but the human brain is still mostly unexplored or virtually inaccessible. Stanley and his GTNeuro colleagues are out there, making their way and charting new paths in a gray matter frontier.

“How cells interact within the complex networks in our brain and nervous system underlies many diseases and disorders,” Stanley says. “The advent of new tools for dissecting circuits within the nervous system gives us, for the first time, the ability to actually ‘see’ and interact with the networks in a very specific and precise manner, perhaps leading to new insights and discoveries for treating a range of neurological disorders and diseases.”

 

LINKS:

GTNeuro

Neural Design Suite

Neural Engineering Center

Neuromechanics Lab at Emory

Center for Advanced Brain Imaging

 

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

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Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

February 27, 2017 | Atlanta, GA

Alzheimer’s disease, and other neurodegenerative conditions involving abnormal folding of proteins, may help explain the emergence of life – and how to create it.

Researchers at Emory University and Georgia Tech demonstrated this connection in two new papers published by Nature Chemistry: “Design of multi-phase dynamic chemical networks” and “Catalytic diversity in self-propagating peptide assemblies.”

“In the first paper we showed that you can create tension between a chemical and physical system to give rise to more complex systems. And in the second paper, we showed that these complex systems can have remarkable and unexpected functions,” said David Lynn, a systems chemist at Emory who led the research. “The work was inspired by our current understanding of Darwinian selection of protein misfolding in neurodegenerative diseases.”

The Lynn lab is exploring ways to potentially control and direct the processes of these proteins – known as prions – adding to knowledge that might one day help to prevent disease, as well as open new realms of synthetic biology. For the current papers, Emory collaborated with the research group of Martha Grover, a professor in the Georgia Tech School of Chemical & Biomolecular Engineering, to develop molecular models for the processes.

Darwin’s theory of evolution by natural selection is well-established – organisms adapt over time in response to environmental changes. But theories about how life emerges – the movement through a pre-Darwinian world to the Darwinian threshold – remain murkier.

The researchers started with single peptides and engineered in the capacity to spontaneously form small proteins, or short polymers. “These protein polymers can fold into a seemingly endless array of forms, and sometimes behave like origami,” Lynn explained. “They can stack into assemblies that carry new functions, like prions that move from cell-to-cell, causing disease.” 

This protein misfolding provided the model for how physical changes could carry information with function, a critical component for evolution. To try to kickstart that evolution, the researchers engineered a chemical system of peptides and coupled it to the physical system of protein misfolding. The combination results in a system that generates step-by-step, progressive changes, through self-driven environmental changes.

“The folding events, or phase changes, drive the chemistry and the chemistry drives the replication of the protein molecules,” Lynn said. “The simple system we designed requires only the initial intervention from us to achieve progressive growth in molecular order. The challenge now becomes the discovery of positive feedback mechanisms that allow the system to continue to grow.”

The researchers used mathematical modeling to help guide the experimental work.

“Modeling requires us to formulate our hypotheses in the language of mathematics, and then we use the models to design further experiments to test the hypotheses,” said Grover. “In this project, the hypotheses were sometimes invalidated by these further experiments, but ultimately this led us to a better understanding of the underlying chemical and physical events and their interactions."

The research was funded by the McDonnell Foundation, the National Science Foundation’s Materials Science Directorate, Emory University’s Alzheimer’s Disease Research Center, the National Science Foundation’s Center for Chemical Evolution and the Office of Basic Energy Sciences of the U.S. Department of Energy.

Additional co-authors of the papers include: Toluople Omosun, Seth Childers, Dibyendu Das and Anil Mehta (Emory Departments of Chemistry and Biology); Ming-Chien Hsieh (Georgia Tech School of Chemical & Biomolecular Engineering); and Neil Anthony and Keith Berland (Emory Department of Physics).

- Written by Carol Clark, Emory University

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February 27, 2017 | Atlanta, GA

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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25th annual gathering at the Petit Institute featured ground-breaking research in neuroscience

February 24, 2017 | Atlanta, GA

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

Suddath Award

GTNeuro

 

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

For More Information Contact

Jerry.grillo@ibb.gatech.edu

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

The professor of chemistry and biochemistry and College of Sciences’ associate dean is the unanimous choice for recognition by the University System of Georgia

February 15, 2017 | Atlanta

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.”

For More Information Contact

maureen.rouhi@cos.gatech.edu

A. Maureen Rouhi, Ph.D.
Director of Communications
College of Sciences

The James A. Carlos Family Chair for Pediatric Technology opens new doors to lifesaving research in pediatric medicine

February 15, 2017 | Atlanta, GA

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

For More Information Contact

maureen.rouhi@cos.gatech.edu

A. Maureen Rouhi, Ph.D.
Director of Communications 
College of Sciences

The School of Biological Sciences alumnus is a member of the College of Sciences Advisory Board

February 7, 2017 | Atlanta

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 More Information Contact

maureen.rouhi@cos.gatech.edu

A. Maureen Rouhi, Ph.D
Director of Communications
College of Sciences

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