May 7, 2018 | Atlanta, GA

Using an informatics tool that identifies “hotspots” of post-translational modification (PTM) activity on proteins, researchers have found a previously-unknown mechanism that puts the brakes on an important cell signaling process involving the G proteins found in most living organisms.

The mechanism, dubbed a “tail,” is part of a small protein known mostly for its role in attaching larger structures to the cell membrane. When researchers inactivated the tail, a signaling response that had previously taken 30 minutes to occur happened almost immediately – with an intensity four times greater than normal.

The research took place in yeast, but if a similar process occurs in human G proteins, the discovery could provide a new drug target for controlling important cellular processes – and potentially offer a new class of biosensors able to more sensitively detect and respond to certain chemical agents. The research, supported by the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS), was reported May 1 in the journal Cell Reports.

“We have discovered the mechanism that regulates how quickly a pathway gets turned on by an external stimulus,” said Matthew Torres, an associate professor in the School of Biological Sciences at the Georgia Institute of Technology. “By genetically altering the control mechanism underlying this process, we are able to modulate how much of a signal from outside the cell gets inside the cell and how quickly it gets through. It’s all the more astonishing because this mechanism has been hiding in plain sight for decades.”

G proteins, also known as guanine nucleotide-binding proteins, are a family of molecules that operate as molecular switches inside cells. They transmit signals acquired from a variety of extracellular stimuli to the interior of a cell – through the membrane, which otherwise wouldn’t allow communication.

The tail found by Torres and Doctoral Candidate Shilpa Choudhury likely escaped attention because it is flexibly attached to the G protein gamma subunit of a closely-collaborating protein team known as G beta/gamma. Protein structures have generally been identified by X-ray crystallography techniques which cannot resolve structures that are in motion. 

Prior to their work, the G gamma subunit has been known primarily as the protein that connects the larger G beta subunit to the cell membrane. Without the work of SAPH-ire – an informatics program that maps PTM activity using machine learning – the role of the tail structure might not have been identified.

“For years, people had focused on G beta/gamma as a complete unit, and not as separate components,” said Choudhury, the paper’s first author. “The gamma is a tiny protein compared to the larger G beta subunit, but we now know that it has a major role in the activity of the signaling system.”

In yeast, G beta/gamma subunits activate a signaling pathway in response to pheromones, a process which normally takes about 30 minutes after stimulation of a pheromone receptor at the cell membrane. Torres and Choudhury suspected that protein modifications, PTMs, were somehow causing the delay. Their computer program SAPH-ire – developed in the Torres lab and announced in 2015 – pointed the finger straight at the G gamma subunit.

The program analyzes existing meta-data repositories of protein sequence and PTM activity to reveal “hotspots” of protein alteration. SAPH-ire was designed to accelerate the search for important regulatory targets on protein structures and to provide a better understanding of how proteins communicate with one another inside cells.

Pulling from worldwide PTM databases that use mass spectrometry to identify sequences that are chemically altered, SAPH-ire pointed to a specific location on the G gamma protein. Using genetic mutation techniques, Choudhury modified a section of the protein to render the tail structure inactive. 

But removing the tail from the process by itself wasn’t enough. To activate the signaling process, structures on the tail had to interact with a separate effector protein. When both were inactivated, the researchers saw a dramatic effect when the receptor was stimulated.

“You can think of the signaling pathway like a wheel travelling down a hill where two pads of the bicycle brake are gripping the wheel to slow it down,” said Torres. “Activating the pheromone receptor is like releasing the wheel down the hill. When both brakes are active, the wheel moves very slowly because the two brakes are working together to slow its speed and momentum. This turns out to be how the pathway behaves in normal cells immediately after receptor stimulation.” 

“If you take away one of the brakes, you get partial braking and the wheel is allowed to move slightly faster, but is still restrained from moving as fast as it can. This is how the pathway behaves in normal cells within the first 20 minutes after receptor stimulation. But if you eliminate both brakes, releasing the wheel down the hill results in very high speed and momentum – kind of like a golf cart without a governor.” 

This is exactly what happened when Choudhury prevented PTMs on both G gamma and the effector protein. “When we do that, we see a rapid activation of the signaling pathway that occurs six times faster, and is four times more intense than with the normal condition with the pathway brakes intact.”

Beyond identifying the control mechanism for the pathway, the researchers also learned how it controls the ability of yeast to respond to pheromones in a “switch-like” manner that is either on or off versus an analog manner that is analogous to a volume knob on a stereo. 

While Torres and Choudhury made their discovery in yeast, they believe it will have broad implications because all organisms that have G proteins, including humans, have G gamma tails that are riddled with PTMs. Among the next steps will be to see if the same type of braking system is exhibited by G gamma subunits and G beta/gamma effectors in human cells. If so, that could provide insights that could identify potentially new drug targets.

“The tail exists, and it’s important in this process of controlling interactions with G beta/gamma effectors, which are essential for turning on signaling pathways,” Torres said. “We suspect the importance of G gamma as a regulator G protein signaling will extend beyond any single organism.”

This research was supported by the National Institutes of Health’s National Institute of General Medical Sciences (NIGMS) grants R01GM117400 and R00GM094533. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

CITATION: Shilpa Choudhury, Parastoo Baradaran-Mashinchi and Matthew Torres, “Negative Feedback Phosphorylation of Gy Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast,” (Cell Reports, 2018). https://doi.org/10.1016/j.celrep.2018.03.135

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Annual two-day event showcases thought leaders in microbiology research from Georgia Tech and beyond

February 4, 2018 | Atlanta, GA

There are vast, invisible, churning communities of organisms living all around and inside every living thing on Earth, overwhelmingly outnumbering us. We can’t see them, but their influence is profound – their processes can connect us, sustain us, protect us, or destroy us.

They are the bacteria, fungi, viruses and other microbes that comprise the world’s many microbiomes, which were the focus of this year’s Suddath Symposium (Jan. 30-31) at the Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology.

“A microbiome is, generally, the collection of interacting microbes in a particular location, and the locations vary in scale,” said Brian Hammer, associate professor in Georgia Tech’s School of Biological Sciences and a Petit Institute researcher.

Hammer and Frank Stewart, also a Petit Institute researcher, were co-chairs of what may have been the best-attended Suddath Symposium in the event’s 26-year history. Every session, for all 12 speakers, featured standing-room crowds in the Suddath Room, in addition to people watching the simulcast in the Petit Institute atrium, and across campus – symposium seating was sold out before the early registration deadline, in early January.

It was an opportunity to showcase work being done at Georgia Tech and across the country and the attendance reflected growing and diverse interest in microbial science.

“Over the last five years or so, the importance of and interest in microbial science at Georgia Tech has really increased,” said Stewart, associate professor in the School of Biological Sciences. “We’ve added faculty, resources, the field is growing. All of those things are coming together right now.”

 

Microbes Are Popular

The topic of microbiomes has infiltrated public consciousness – this is a popular subject, Hammer said. “You’ll see microbiome research in high profile journals every week now, it’s one of those things that’s made it into the mainstream. You go home and your parents are starting to ask about these things. Everybody seems to care about their microbiomes, and we’re all trying to figure out how these things work, and we’re right at the forefront here at Tech.”

The interest, like the science, is deep and wide. For instance, there’s a lot of research into the microbiomes of the human gut and lungs, much of it fueled by initiatives like the ongoing NIH Human Microbiome Project. Meanwhile, there’s the Earth Microbiome Project, across ecologies and habitats and environments.

“There are so many scales, some more narrowly focused, some broader, and we tried to reflect that range of interest in this symposium,” Hammer said.

The symposium, which was entitled, “The Chemical Ecology of Microbiome Interactions,” presented research unified by the goal of understanding microbe-microbe and microbe-host interactions, spanning diverse specialties, including biomedicine and genomics, chemical ecology, biogeochemical cycling, environmental science, biophysics, and the evolution of microbial interactions, including those involving pathogens.

 

Two Days of Brain Candy

Accordingly, the symposium drew speakers who are among the nation’s thought leaders in both environmental and human microbiome research (including several from Georgia Tech), presenting their research over, “two days of brain candy,” which is how Bonnie Bassler of Princeton University described the gathering.

“It was a thrill,” said Bassler. “There was such a diverse range of science discussed, and every speaker still made sure that everyone understood their talks, which is remarkable when you consider the range of topics.”

As tradition demands, the two-day symposium began with a research presentation from the grad student who was named the Suddath Award winner during the Petit Institute holiday party back in December. These presentations often have little connection with the symposium theme. This year, David Hanna, a doctoral candidate in the lab of Petit Institute researcher Amit Reddi, presented his research, entitled, “Shedding Light on Heme Signaling Networks with Heme Sensors and Quantitative Mass Spectrometry.”

Then it was all about the many interactions of very tiny things, the contact and communication between microbes. Bassler, who was Hammer’s postdoctoral advisor, led off the microbiome presentations on Tuesday with a talk entitled, "Bacterial Quorum Sensing and its Control."

Bassler is a wet lab microbiologist, said Hammer, and she was followed by a who’s who list of microbial researchers from beyond the Georgia Tech campus. On Tuesday, Jon Clardy, a chemical biologist from Harvard University, spoke on, “Microbiomes, Chemical Ecology, and Animal Development.” Seth Bordenstein, a classically trained evolutionary biologist from Vanderbilt University, delivered a presentation that asked, “How do Microbes Form Relationships With Animals?”

Tuesday’s sessions ended with a presentation from Mary Voytek, a microbiologist who heads up NASA’s Astrobiology Program, that really took the subject to far out places – like, deep onto our solar system, to the moons of Jupiter and Saturn and the search for life beyond Earth, with a talk entitled, “How can Microbiomes Serve as a Model for the Emergence and Early Evolution of Life.”

“Mary is very interested in how microbial systems that we can study on Earth might inform our understanding of how life might look on other planets,” said Stewart.

Mary Ann Moran from the University of Georgia led off Wednesday with her talk, “Chemical Currencies of the Ocean Microbiome,” followed by Tim Read from the Emory School of Medicine, and his presentation, “Pathogen Genomic Variation in the Context of a Human Microbiome.”

Rebecca Vega Thurber from Oregon State University who has focused much of her research on coral systems in the oceans, delivered a presentation entitled, “The Roles of Environmental Nitrogen in Coral Microbiome Dysbiosis and Disease.”

Karine Gibbs, the second speaker from Harvard and the final presenter from outside Georgia Tech, stressed the importance of contact-dependent interactions in her talk, “Know Thy Neighbors: The Influences of Self/Non-Self Recognition on the Collective Migration of a Bacterial Population.”

Gibbs, said Hammer, “was one of the pioneers that figured out bacteria have ways to discriminate self from non-self, and use that information to organize microbial communities.”

Civics at the microscale? No, not quite. But Gibbs, who has observed wholesale warfare between microbial armies, is working with her lab to develop models that clarify the differences between lethal and non-lethal contact dependent interactions. “The predominant theory in microbiology is that all of these interactions would be about death,” Gibbs said. “Our evidence shows that’s not the case.”

 

Tech Researchers Take Stage

A quartet of Georgia Tech researchers also took research center stage – or, center projection screen – during the two-day symposium.

Neha Garg, assistant professor in the School of Chemistry and Biochemistry, gave a talk on Tuesday entitled, “Chemical Chatter between the Cystic Fibrosis-associated Microbiome.” She’s one of the new microbiology-focused faculty members at Georgia Tech, arriving last year following her postdoctoral work at the University of California-San Diego.

“She’s studying the lungs of people with cystic fibrosis, trying to understand the nature of the chemical compounds that organisms use to interact with other micro-organisms, or a host,” Hammer said.

While most researchers engaged in this area would typically remove the organisms that cause a bacterial infection in a cystic fibrosis patient, and study them in a petri dish, Garg has developed a method to study all of the bacterial chemicals in an infected lung, based on their DNA.

“She’s doing it spatially, building a three-dimensional map of the infected lung,” Hammer said. “She’s taking the research to the next level.”

The other three Georgia Tech researchers were part of the Wednesday lineup.

Joel Kostka, professor and associate chair of research in the School of Biological Sciences, delivered a talk called, “The Sphagnum Phytobiome: Ecosystem Engineers of the Global Carbon Cycle.”

“Joel is one of the leaders in thinking about microbes in real world environmental settings, which are often quite diverse,” Stewart said. “He studies systems ranging from the Gulf of Mexico to the Arctic. He combines a wide range of approaches in thinking about the system holistically.”

Petit Institute researcher James Gumbart, from the School of Physics, talked about, “Molecular Mechanisms of Nutrient Acquisition and Virulence Revealed by Molecular Dynamics Simulations.”

Gumbart is one of that breed of physicist who calls himself a ‘squishy,’ according to Hammer. “They work in ‘squishy physics.’ His expertise is in using mathematical simulations to look at these molecular machines that bacteria use to interact with one another,” Hammer said.

The last speaker of the symposium was Marvin Whiteley, a professor in the School of Biology and the Emory School of Medicine, whose talk was entitled, “Biogeography of in vivo Biofilms.”

Like Hammer, Whiteley was trained as a classical bacterial geneticist, “which is, you take an organism and dissect it at the level of DNA to figure out how it’s capable of accomplishing certain tasks,” Hammer said. “Marvin has transitioned in the last 10 to 15 years to focusing on the organism that causes disease in cystic fibrosis patients.”

At some point, Whiteley’s work in cystic fibrosis as a geneticist would ideally dovetail with Garg’s work in the same disease as a chemist. That isn’t by accident.

“That’s an example of complementary expertise that Georgia Tech is bringing together,” Hammer said. And it gets to the heart of the reason for this topic at this symposium at this time. “We’ve reached a stage now where these interactions are allowing us to move the science forward in ways we weren’t able to at Georgia Tech until fairly recently. We think we’re at a turning point.”

Microbiology, the study of the smallest living organisms, is playing an increasingly expanded role in the further understanding of life, and how it evolves, thrives, or doesn’t. As she left to catch a plane back to Boston, Gibbs thought about the two days of multifaceted brain candy, and its impact on her.

“This was an amazing community of science,” she said. “The breadth of it! This was a nice reflection of the dynamics that are in place right now in microbiology, and I think it helped illustrate how microbes, whether we like it or not, are integral to so many aspects of our lives and our living planet.”

 

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January 8, 2018 | Atlanta, GA

Psssst, mud crabs, time to hide because blue crabs are coming to eat you! That’s the warning the prey get from the predators’ urine when it spikes with high concentrations of two chemicals, which researchers have identified in a new study.

Beyond decoding crab-eat-crab alarm triggers, pinpointing these compounds for the first time opens new doors to understanding how chemicals invisibly regulate marine wildlife. Insights from the study by researchers at the Georgia Institute of Technology could someday contribute to better management of crab and oyster fisheries, and help specify which pollutants upset them.

In coastal marshes, these urinary alarm chemicals, trigonelline and homarine, help to regulate the ecological balance of who eats how many of whom -- and not just crabs.

Blue crabs, which are about hand-sized and are tough and strong, eat mud crabs, which are about the size of a silver dollar and thin-shelled. Mud crabs, on the other hand, eat a lot of oysters, but when blue crabs are going after mud crabs, the mud crabs hide and freeze, so far fewer oysters get eaten than usual.

Humans are part of the food chain, too, eating oysters as well as blue crabs that boil up a bright orange. The blue refers to the color of markings on their appendages before they’re cooked. Thus, the blue crab urinary chemicals influence seafood availability for people, as well.

Predator pee-pee secrets

The fact that blue crab urine scares mud crabs was already known. Mud crabs duck and cover when exposed to samples taken in the field and in the lab, even if the mud crabs can’t see the blue crabs yet. Digestive products, or metabolites, in blue crab urine trigger the mud crabs’ reaction, which also makes them stop foraging for food themselves.

“Mud crabs react most strongly when blue crabs have already eaten other mud crabs,” said Julia Kubanek, who co-led the study with fellow Georgia Tech professor Marc Weissburg. “A change in the chemical balance in blue crab urine tells mud crabs that blue crabs just ate their cousins,” Kubanek said.

Figuring out the two specific chemicals, trigonelline and homarine, that set off the alarm system, out of myriad candidate molecules, is new and has been a challenging research achievement.

“My guess is that there are many hundreds of chemicals in the animal’s urine,” said Kubanek, who is a professor in Georgia Tech’s School of Biological Sciences, in its School of Chemistry and Biochemistry, and who is also Associate Dean for Research in Georgia Tech’s College of Sciences.

The researchers applied technology and methodology from metabolomics, a relatively new field used principally in medical research to identify small biomolecules produced in metabolism that might serve as early warning signs of disease. Kubanek, Weissburg, and first author Remington Poulin published their results the week of January 8, 2017, in the journal Proceedings of the National Academies of Science.

The research was funded by the National Science Foundation.

Peedle in a haystack

Trigonelline has been studied, albeit loosely, in some diseases, and is known as one of the ingredients in coffee beans that, upon roasting, breaks down into other compounds that give coffee its aroma. Homarine is very similar to trigonelline, and, though apparently less studied, it’s also common.

“These chemicals are found in many places,” Kubanek said. But picking them out of all those chemicals in blue crab urine for the first time was like finding two needles in a haystack.

Often, in the past, researchers trying to narrow down such chemicals have started out by separating them out in arduous laboratory procedures then testing them one at a time to see if any of them worked. There was a good chance of turning up nothing.

The Georgia Tech researchers went after all the chemicals at one time, the whole haystack, using mass spectrometry and nuclear magnetic resonance spectroscopy.

“We screened the entire chemical composition of each sample at once,” Kubanek said. “We analyzed lots and lots of samples to fish out chemical candidates.”

Crabs are ‘walking noses’

The researchers discovered spikes in about a dozen metabolites after blue crabs ate mud crabs. They tested out those pee chemicals that spiked on the mud crabs, and trigonelline and homarine distinctly made them crouch.

“Trigonelline scares the mud crabs a little bit more,” Kubanek said.

More specifically, high concentrations of either of the two did the trick. “It’s clear that there was a dose-dependent response,” said Weissburg, who is a professor in Georgia Tech’s School of Biological Sciences. “Mud crabs have evolved to hone in on that elevated dose.”

“Most crustaceans are walking noses,” Weissburg said. “They detect chemicals with sensors on their claws, antennae and even the walking legs. The compounds we isolated are pretty simple, which suggests they might be easily detectable in a variety of places on a crab. This redundancy is good because it increases the likelihood that the mud crabs get the message and not get eaten.”

Ecological and fishery effects

Evolution preserved the mud crabs with the duck-and-cover reaction to the two chemicals, which also influenced the ecological balance, in part by pushing blue crabs to look for more of their food elsewhere. But it influenced other animal populations as well.

“These chemicals are staggeringly important,” Weissburg said. “The scent from a blue crab potentially affects a large number of mud crabs, all of which stop eating oysters, and that helps preserve the oyster populations.”

All of that also impacts food sources for marine birds and mammals: Just by the effects of two chemicals, and there are so many more chemical signals around. “It’s hard for us to appreciate the richness of this chemical landscape,” Weissburg said.

As scientists learn more, influencing these systems could become useful to ecologists and the fishing industry.

“We might even be able to use these chemicals to control oyster consumption by predators to help preserve these habitats, which are critical, or to help oyster farmers. That’s becoming important in Georgia fisheries,” Weissburg said.

Pollutants in pesticides and herbicides are known to interfere with estuaries’ ecologies. “It will be a lot easier to test how strong this is by knowing specific ecological chemicals,” Weissburg said.

Fear-o-mone small molecules

By the way, trigonelline and homarine are not pheromones.

“Pheromones are signaling molecules that have a function within the same species, like to attract mates,” Kubanek said. “And blue crabs and mud crabs are not the same species.”

“In this case, the mud crabs have evolved to chemically eavesdrop on the blue crabs’ pee. You might call trigonelline and homarine fear-inducing cues.”

Identifying such metabolites, also called small molecules, and their effects is the latest chapter in constructing the catalog of life molecules. “Everyone knows about the human genome project, identifying genomes; then came transcriptomes (molecules that transcribe genes),” Kubanek said. “Now we’re pretty far along with proteomics (identifying proteins), but we’re just now figuring out metabolomes.”

The paper was co-authored by Serge Lavoie, Katherine Siegel, and David Gaul. The research was funded by the National Science Foundation Division of Ocean Sciences (grant OCE-1234449). 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 sponsor.

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December 28, 2017 | Atlanta, GA

Got a sore throat? The doctor may write a quick prescription for penicillin or amoxicillin, and with the stroke of a pen, help diminish public health and your own future health by encouraging bacteria to evolve resistance to antibiotics.

It’s time to develop alternatives to antibiotics for small infections, according to a new thought paper by scientists at the Georgia Institute of Technology, and to do so quickly. It has been widely reported that bacteria will evolve to render antibiotics mostly ineffective against them by mid-century, and current strategies to make up for the projected shortfalls haven’t worked.

One possible problem is that drug development strategies have focused on replacing antibiotics in extreme infections, such as sepsis, where every minute without an effective drug increases the risk of death. But the evolutionary process that brings forth antibiotic resistance doesn’t happen nearly as often in those big infections as it does in the multitude of small ones like sinusitis, tonsillitis, bronchitis, and bladder infections, the Georgia Tech researchers said.

“Antibiotic prescriptions against those smaller ailments account for about 90 percent of antibiotic use, and so are likely to be the major driver of resistance evolution,” said Sam Brown, an associate professor in Georgia Tech’s School of Biological Sciences. Bacteria that survive these many small battles against antibiotics grow in strength and numbers to become formidable armies in big infections, like those that strike after surgery.

“It might make more sense to give antibiotics less often and preserve their effectiveness for when they’re really needed. And develop alternate treatments for the small infections,” Brown said.

Brown, who specializes in the evolution of microbes and in bacterial virulence, and first author Kristofer Wollein Waldetoft, a medical doctor and postdoctoral research assistant in Brown’s lab, published an essay detailing their suggestion for refocusing the development of bacteria-fighting drugs on December 28, 2017, in the journal PLOS Biology.

Duplicitous antibiotics

The evolution of antibiotic resistance can be downright two-faced.

“If you or your kid go to the doctor with an upper respiratory infection, you often get amoxicillin, which is a relatively broad-spectrum antibiotic,” Brown said. “So, it kills not only strep but also a lot of other bacteria, including in places like the digestive tract, and that has quite broad impacts.”

E. coli is widespread in the human gut, and some strains secrete enzymes that thwart antibiotics, while other strains don’t. A broad-spectrum antibiotic can kill off more of the vulnerable, less dangerous bacteria, leaving the more dangerous and robust bacteria to propagate.

“You take an antibiotic to go after that thing in your throat, and you end up with gut bacteria that are super-resistant,” Brown said. “Then later, if you have to have surgery, you have a problem. Or you give that resistant E. coli to an elderly relative.”

Much too often, superbugs have made their way into hospitals in someone’s intestines, where they had evolved high resistance through years of occasional treatment with antibiotics for small infections. Then those bacteria have infected patients with weak immune systems.

Furious infections have ensued, essentially invulnerable to antibiotics, followed by sepsis and death.

Alternatives get an “F”

Drug developers facing dwindling antibiotic effectiveness against evolved bacteria have looked for multiple alternate treatments. The focus has often been to find some new class of drug that works as well as or better than antibiotics, but so far, nothing has, Brown said.

Wollein Waldetoft came across a research paper in the medical journal Lancet Infectious Diseases that examined study after study on such alternate treatments against big, deadly infections.

“It was a kind of scorecard, and it was almost uniformly negative,” Brown said. “These alternate therapies, such as phage or anti-virulence drugs or, bacteriocins -- you name it -- just didn’t rise to the same bar of efficacy that existing antibiotics did.”

“It was a type of doom and gloom paper that said once the antibiotics are gone, we’re in trouble,” Brown said. “Drug companies still are investing in alternate drug research, because it has gotten very, very hard to develop new effective antibiotics. We don’t have a lot of other options.”

But the focus on new treatments for extreme infections has bothered the researchers because the main arena where the vast portion of resistance evolution occurs is in small infections. “We felt like there was a disconnect going on here,” Brown said.

Don’t kill strep, beat it

The researchers proposed a different approach: “Take the easier tasks, like sore throats, off of antibiotics and reserve antibiotics for these really serious conditions.”

Developing non-antibiotic therapies for strep throat, bladder infections, and bronchitis could prove easier, thus encouraging pharmaceutical investment and research.

For example, one particular kind of strep bacteria, group A streptococci, is responsible for the vast majority of bacterial upper respiratory infections. People often carry it without it breaking out.

Strep bacteria secrete compounds that promote inflammation and bacterial spread. If an anti-virulence drug could fight the secretions, the drug could knock back the strep into being present but not sickening.

Brown cautioned that strep infection can lead to rheumatic heart disease, a deadly condition that is very rare in the industrialized world, but it still takes a toll in other parts of the world. “A less powerful drug can be good enough if you don’t have serious strep throat issues in your medical history,” he said.

Sometimes, all it takes is some push-back against virulent bacteria until the body’s immune system can take care of it. Developing a spray-on treatment with bacteriophages, viruses that attack bacteria, might possibly do the trick.

If doctors had enough alternatives to antibiotics for the multitude of small infections they treat, they could help preserve antibiotic effectiveness longer for the far less common but much more deadly infections, for which they’re most needed.

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Research was funded by the Simons Foundation (grant 396001), the Centers for Disease Control and Prevention (grant OADS-2016-N-17812), the Wenner-Gren Foundation, and the Physiographic Society of Lund. 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.

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Emily Siegfried comes from a family with Georgia Tech ties for more than 100 years

December 13, 2017 | Atlanta, GA

When Emma Siegfried graduates this weekend, she’ll be the latest in a line of family members who have been attending Georgia Tech for more than 100 years.

The fourth-generation Tech student and metro Atlanta native grew up hearing about Tech and visiting campus. Even with a mom and many other family members as alumni, though, she wasn’t sure Georgia Tech was for her until she actually enrolled in Fall 2013. At a football game against North Carolina that semester, something clicked.

“Feeling the excitement and energy at the game and with everyone in the stadium, I remember feeling like, ‘OK, I can be part of this,’” she said. “It felt like home.”

Siegfried’s love of Tech spirit led her to the Ramblin' Reck Club, which she joined the following spring — also following in her mother’s footsteps. 

“My mom never pushed Tech, but once I got here and joined Reck Club, she started telling me more about it,” Siegfried said. “Sharing that has been cool. I’ve even met people through Reck Club who knew my mom when they were in college.”

Siegfried has also charted her own path here, though. As a second-year student, she found herself responsible for planning the national club swim and dive championship, held annually at the McAuley Aquatic Center. The event brings 1,600 people to campus and had never been planned by a student before.

“Executing that made me realize the potential and ability I have to do big things, even if I don’t feel prepared,” she said. In her fourth year, Siegfried helped establish Georgia Tech’s Kappa Alpha Theta chapter, the first new sorority on campus since 2008.

In all her involvement, Siegfried has felt most at home here because of the people.

“Everyone is nerdy and quirky in their own way,” she said. “I was that girl in high school, and then I got here, and everyone is like that. I love it.”

Siegfried will earn her bachelor’s degree in biology this week and has her sights set on graduate school for marine science. Studying biology at a landlocked university, she made the choice to spend one semester across the world in Sydney, Australia.

“I’d encourage everyone to study abroad,” she said. “It’s the best thing I’ve done here. Being so close to the Great Barrier Reef was awesome.”

When she crosses the stage next week, Siegfried will not only be sharing McCamish Pavilion with thousands of graduates and dozens of close friends, but also with the spirit of family history that preceded her.

Editor's Note: This story was adapted from an article published by the Georgia Tech News Center. For the original story, additional photos, and a video of Emma Siegfried, see the original posting.

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Ph.D. applied physiology graduate exemplifies service to country

December 15, 2017 | Atlanta, GA

Georgia Tech’s motto of Progress and Service is emulated by its student body, and several students graduating this December have shown a passion for service while studying at Tech.

Joshua Jarrell is among the students walking this week who have given back to their communities in significant ways. He exemplifies service to country.

Jarrell enrolled as a Ph.D. candidate in Fall 2012. He began his service journey during his senior year of high school when he enlisted in the Army Reserves as a construction engineer. After completing undergraduate work at Auburn University, he transferred to the Alabama National Guard to become a medic.

Jarrell, who is earning a Ph.D. in applied physiology, has balanced military service with his studies. In 2015, he had to withdraw from Tech when his Guard unit was mobilized and deployed in northern Iraq.

“During my deployment, I helped train soldiers in combat medicine to support them in their fight against ISIS,” he said.

“Too often veterans just accept the first decent position they’re offered and then struggle to move up in the company or to another field.”

While at Tech, Jarrell joined the Georgia Tech chapter of Student Veterans of America. He enjoyed spending time with the group of veterans and sponsor, David Ross.

“It was nice to sit back and relax in the company of other veterans amid the stresses of graduate work,” he said. Overall, Jarrell had found the community at Tech to be supportive of his service. “When I came back from my deployment, my lab mates and advisor extended themselves in many ways to get me caught up in our field and help get my research going again.”

In the future, Jarrell hopes to develop a program to encourage veterans to pursue higher education before their next career transition.

“Too often veterans just accept the first decent position they’re offered and then struggle to move up in the company or to another field," he explained. "Getting that next degree will set up a veteran for extended success in the civilian world.”

Editor's Note: This article was excerpted from a story published by Georgia Tech News Center on Dec. 14, 2017.

For More Information Contact

Julia Faherty 
Institute Communications 

November 27, 2017 | Atlanta, GA

Genetic mutation may drive evolution, but not all by itself. Physics can be a powerful co-pilot, sometimes even setting the course.

In a new study, physicists and evolutionary biologists at the Georgia Institute of Technology have shown how physical stress may have significantly advanced the evolutionary path from single-cell to multicellular organisms. In experiments with clusters of yeast cells called snowflake yeast, forces in the clusters’ physical structures pushed the snowflakes to evolve.

“The evolution of multicellularity is as much a matter of physics as it is biology,” said biologist Will Ratcliff, an assistant professor in Georgia Tech’s School of Biological Sciences.

The bigger they are…

Like the first ancestors of multicellular organisms, in this study the snowflake yeast found itself in a conundrum: As it got bigger, physical stresses tore it into smaller pieces. So, how to sustain the growth needed to evolve into a complex multicellular organism?

In the lab, those shear forces played right into evolution’s hands, laying down a track to direct yeast evolution toward bigger, tougher snowflakes.

“In just eight weeks, the snowflake yeast evolved larger, more robust bodies by figuring out soft matter physics that took humans hundreds of years to learn,” said Peter Yunker, an assistant professor in Georgia Tech’s School of Physics. He and Ratcliff collaborated on the research that documented the evolution and measured the physical properties of mutated snowflake yeast.

They published their results on November 27, 2017, in the journal Nature Physics. The work was funded by the NASA Exobiology program, the National Science Foundation, and a Packard Foundation Fellowship to Ratcliff.

Questions and answers

Here are some questions and answers to illuminate the study and its significance.

But first, some background: Baker’s yeast, which was used in these experiments, is usually a single-cell organism. Yeast cells with a well-known mutation stick together in groups called snowflakes.

That was not the focus of the experiments, but the yeast snowflakes were the starting point in this study on the evolution of multicellularity.

Why is this study significant?

Such a cell cluster like a yeast snowflake is not a well-integrated multicellular organism yet. To make it to even simple multicellularity like that of some algae is a very long evolutionary haul.

“It’s a journey of a thousand steps,” Ratcliff said. “The key change is for this group of cells not to evolve as a gang of single cells but as one multicellular individual.”

In this work, the researchers showed how snowflake yeast took first steps in that direction by evolving more resilient multicellular bodies that sustained growth. The process was mainly driven by physical forces, as the simple snowflakes did not have complex inner biological workings that were capable of being the main drivers.

“This is an amazing example of multicellular adaptation around physical constraints well before the evolution of a cellular developmental program,” Yunker said.

How does this evolution via physical stress work?

“Yeast snowflakes grew by adding cells end to end to form branches kind of like those of a bush,” Yunker said. “But the branches crowded each other, and the stresses that result made some break off.”

The breakage chopped down the size of individual yeast snowflakes, but after multiple generations, the snowflakes evolved to reduce the crowding of branches by elongating its individual cells.

As a result, the overall snowflakes were less stressed and could grow larger and more robust.

In addition, Georgia Tech researchers discovered that physics made the snowflakes basically have babies. Specifically, the pieces that broke off became propagules that grew into snowflakes of their own.

This reproduction was created by physical force and not by a biological program. Ratcliff published a separate study about the reproduction aspect on October 23, 2017, in the journal Philosophical Transactions of the Royal Society B.

“Physics does a lot for multicellularity,” Ratcliff said. “It also gives it a lifecycle.” Lifecycle refers to birth, growth, reproduction, and death.

“A consensus is forming that for something to really evolve to multicellularity, very early on, a multicellular lifecycle has to develop.”

Also READ: Evolution, What was the Primordial Stew?

How did the experiments select for these specific adaptations?

Ratcliff and Yunker streamlined evolution in the lab by creating a consistent selection regime for the yeast snowflakes to evolve in. In this case, they selected for snowflakes that were best at sinking.

The snowflakes that sank better were heavier, because they grew larger than others in the manner described above, giving them more mass. “The clusters that evolved to grow bigger were therefore also heavier,” Ratcliff said.

This experimental selection setup befitted natural evolution, which also had to select for size to arrive at complex multicellular bodies, which are much, much larger than single cells.

Mutation of branches is genetic. Is physics really so important here?

That’s correct: Random genetic mutations resulted in the better, longer branches in some yeast snowflakes giving them a cumulative weight advantage.

But the propagation of the superior snowflake mutations was the result of physical stresses not breaking the snowflakes until they had grown larger.

The pieces that eventually did break off, due purely to physical force, were the propagules. Some of them carried mutations forward that made the new snowflakes even better at sinking.

And that was a critical step in the multicellular evolution.

How was stress corroborated as the cause of snowflakes splitting apart?

The researchers put the material properties of the snowflakes to the test under an atomic force microscope. “We squished the clusters and measured how much force and energy you needed to break them,” Yunker said.

“The physical measurement indicated closely the size the clusters would attain before they broke off a branch due to stress,” Ratcliff said.

Also READ: 'Cavemen' had better mental health genes?

Coauthors of this study were Shane Jacobeen, Jennifer Pentz, Elyes Graba, and Colin G. Brandys of Georgia Tech. The research was funded by the NASA Exobiology program (grant #NNX15AR33G), the National Science Foundation (grant #IOS-1656549), and a Packard Foundation Fellowship. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of those sponsors.

For More Information Contact

ben.brumfield@comm.gatech.edu

Writer and Media Relations Contact: Ben Brumfield (404-660-1408)

Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia  30332-0181  USA

December 4, 2017 | Atlanta, GA

The American Association for the Advancement of Science (AAAS) has named three researchers from the Georgia Institute of Technology as fellows for 2017 for their contributions to the advancement of science.

Baratunde Cola, Mary Frank Fox, and Joshua Weitz, who are members of AAAS, were elected by their peers to receive the honor and join hundreds of their contemporaries who became fellows this year. “This year 396 members have been awarded this honor by AAAS because of their scientifically or socially distinguished efforts to advance science or its applications,” the AAAS wrote in its announcement of this year’s fellows.

All three Georgia Tech fellows saw the AAAS Fellowship as encouragement to continue serving science and humanity.

The three have excelled in research in the following fields, according to AAAS: Cola in nanoscale engineering, Fox in the participation and performance of women and men in science, and Weitz in virus dynamics in populations and in ecosystems. Here are summaries of the researchers’ achievements and interests.

Baratunda Cola may be best known for engineering the first-ever optical rectenna. A rectenna, or rectifying antenna, turns electromagnetic waves into direct current electricity, and Cola’s invention was the first known to work with sunlight instead of radio waves, making it an innovation in efficient solar energy generation.

Cola, who is an associate professor in The George W. Woodruff School of Mechanical Engineering at Georgia Tech, is currently focused on the transfer of heat, and the conversion of energy in nanostructures, particularly those based on carbon nanotubes. He holds three carbon nanotube related patents and is interested in making his innovations producible on a large scale for practical use.

“I was honored that AAAS chose to recognize my contributions to science over the years,” Cola said. “The fellowship gives a bigger platform to my work so it can reach more people and be useful to them.”

Cola’s vision transcends arbitrary confines of a research field. “I think of myself less as being a mechanical engineer and more as a person concerned with the advancement and well-being of people, and I appreciate the power of science to positively affect lives through practical applications.”

In April, Cola received the highest honor awarded by the National Science Foundation to up-and-coming scientists and engineers. Like the AAAS Fellowship, the Alan T. Waterman award also recognized Cola’s achievements in transforming light and heat into electricity on the nanoscale, and it added $1 million in funding to his research.

Cola also serves as CEO of Carbice Corporation, a Georgia Tech spinoff company that has developed a heat-conducting tape that helps prevent electronic devices from overheating.

Mary Frank Fox is known for her research on women and men in scientific organizations and occupations. She is nationally recognized as a leader on issues of diversity, equity, and equity in science, and her work has had a significant influence on science and technology policy.

Fox, who is an ADVANCE Professor at the School of Public Policy in Georgia Tech’s Ivan Allen College of Liberal Arts, is particularly interested in how social and organizational settings, in which scientists are educated and work, influence their performance. She holds multiple board of director positions in societies connected to science and technology policy.

“I’m deeply honored by the AAAS award,” Fox said. “I value that it recognizes my years of research on women and men in sciences and the policy implications for equity.”

Fox sees the award as recognition that her work advances science and is aligned with AAAS’s commitments. “I’m one of the founders of this area of science, and I value this award recognizing this research that advances science,” Fox said.

Joshua Weitz uses models to predict the effects of viruses on populations and on ecosystems, but his work encompasses many complex biological systems. His group combines methods from physics, math, computational biology, and bioinformatics to develop in-depth analytical models of biological dynamics to understand experimental and environmental data.

In the field of virology, he applies this approach to the molecular workings of viruses, their spread through a population and their evolution into new strains. His work is theoretical, but he uses his detailed computational methods to collaborate with experimentalists. Weitz is a professor in Georgia Tech’s School of Biological Sciences, Courtesy Professor of Physics and the Director of the Interdisciplinary Graduate Program in Quantitative Biosciences.

“When AAAS first informed me, I was honored and humbled.  And I was proud of my group and its collective effort in the last 10 years at Georgia Tech to study viral ecology,” Weitz said.

“The mission of the AAAS is ever more important in these times, and being a fellow gives us a greater responsibility to communicate our research beyond the scientific community, to let the public know how it serves society’s betterment by improving public health and environmental health.”

The American Association for the Advancement of Science lays claim to the distinction of being “the world’s largest general scientific society.” AAAS was founded in 1848 and publishes the journal Science as well as many other prestigious research periodicals. The AAAS Fellowship began in 1874.

For More Information Contact

ben.brumfield@comm.gatech.edu

Writer and Media Relations Contact: Ben Brumfield (404-660-1408)

Georgia Institute of Technology
177 North Avenue
Atlanta, Georgia  30332-0181  USA

Petit Institute core facility at Georgia Tech adds new equipment and services, allowing researchers to dive deeper

November 15, 2017 | Atlanta, GA

Advances in technology have driven the evolution of genome analysis and collaborative research forward at a rapid rate. This is particularly evident within the Petit Institute for Bioengineering and Bioeciences at the Georgia Institute of Technology, where the Genome Analysis Core has added a powerful new tool that allows researchers to look deeper into the gene expression analysis on a single cell level.

“Since we launched in 2012, the core has evolved quite a bit,” says Dalia Arafat-Gulick, who manages the lab of Petit Institute researcher Greg Gibson (professor in the School of Biological Sciences) and the Genome Analysis Core (contained within the Gibson lab space), in the Krone Engineered Biosystems Building. “The usage and diversity of equipment has definitely increased since then, and so have the services we provide.”

It all started with the Fluidigm Biomark quantitative real-time PCR (polymerase chain reaction). PCR, sometimes called “molecular photocopying,” is a fast technique to amplify small segments of DNA. The PCR technique was invented more than 30 years ago and it has transformed the study of DNA – mapping in the Human Genome Project.

PCR can be inexpensive if you’re only looking at a few genes, according to Gibson. “The costs can add up quickly,” he says. “But the Fluidigm platform brings the costs down further.”

This makes it possible, for example, to monitor the expression of 96 genes in 96 samples for around $1,000 (or 10 cents per reaction), “with high accuracy,” Gibson adds.

The latest transformative tool in Georgia Tech’s Genome Analysis Core is the ddSEQ, part of the single-cell sequencing system co-developed by Illumina and Bio-Rad. The Marcus Foundation collaborated with the Petit Institute in providing funding support, as Georgia Tech last April became the first research institution in the Southeast to deploy the ddSEQ.

“The ddSEQ is essentially a sample preparation platform,” explains Steve Woodard, director of core facilities for the Petit Institute. “You’re preparing samples to go downstream for sequencing in the Molecular Evolution Core or the High-Throughput DNA Sequencing Core. Just another example of how our core facilities are integrated.”

The process typically begins upstream in the Cellular Analysis and Cytometry Core, where researchers will utilize flow cytometry to isolate specific cell populations. Then the ddSEQ separates those cells into a sub-nanoliter oil based droplets on a disposable cartridge, in under five minutes, “which gives you a fast turnaround for each cell captured,” Arafat-Gulick says.

Each cartridge can accommodate up to four samples, which allows each sample to be processed simultaneously. Cell lysis, reverse transcription, and bar-coding occur inside the individual droplets, which allow researchers to amplify several thousand transcripts in each cell.

“The next step is to actually get them sequenced,” Arafat-Gulick says. “That’s where the downstream cores [High Throughput and Molecular Evolution] come in. They have the equipment that allows us to ultimately analyze the gene expression levels of these cells.” 

In this way, researchers can peek inside hundreds – or even thousands – of cells, seeing how much diversity in the mixture there is, or monitoring how individual cells are responding to treatments, all for around $10 a cell. The technology also exists to sequence the DNA, and measure methylation states of genes, “which is transforming genomic analysis,” Gibson says.

“The next step is to actually get them sequenced,” Arafat-Gulick says. “That’s where the downstream cores [High Throughput and Molecular Evolution] come in. They have the equipment that allows us to ultimately analyze the gene expression levels of these cells.”

A number of Petit Institute researchers, including Krish Roy, Ed Botchwey, and Gibson, are working in the single-cell arena now, utilizing the equipment, techniques, and services available through the Genome Analysis Core.

“It’s a quantitative way to look at RNA sequencing on a single cellular level,” Arafat-Gulick says. “Principal investigators really want to see what’s happening on a cell to cell basis, and this new technology makes this accessible, at a much faster rate than before.”

•••

The Petit Institute's state-of-the-art research facilities, known as "Core Facilities," serve as a shared resource for the bioengineering and bioscience community. Consultation, training, and technical support is available for a variety of research projects. Users have access to over 100 pieces of lab equipment totaling over $24 million. 

Learn more about the Petit Institute’s core facilities and how they can support your research projects. 

 

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

Advancing Georgia Tech’s inclusivity through grassroots initiatives

November 20, 2017 | Atlanta, GA

Minda Monteagudo noticed a lack of spaces and programming for women of color on campus. So she applied for a Diversity and Inclusion Fellowship to explore ways to meet the need.

Inspired by the example of African-American musician Daryl Davis, Conan Zhao hopes to use his diversity fellowship to explore the use of music in breaking barriers among people.

Monteagudo and Zhao are among six members of the College of Sciences community to be named 2018 Diversity and Inclusion Fellows. The program brings together faculty, staff, and students who individually and collectively advance their action, research, or teaching objectives while enhancing the culture of inclusive excellence at Tech.

Altogether the 2018 fellows from the College of Sciences are:

The 2018 fellows were announced on Nov. 15 at a poster session showcasing the projects of the program’s inaugural 2017 cohort.

Among the 2017 fellows were three from the College of Sciences:

  • Jennifer Beveridge, a Ph.D. candidate supervised by School of Chemistry and Biochemistry (Chem/Biochem) Professor and Chair M.G. Finn
  • Calvin Runnels, a third-year biochemistry major who conducts research with Chem/Biochem Professor Loren Williams
  • Hussein Sayani, a former Ph.D. student of EAS Professor Kim Cobb, now a postdoctoral researcher in Boston University

The 2017 fellows’ projects inspired and encouraged the second cohort and the audience.

Beveridge partnered with Santanu Dey, associate professor in the H. Milton Stewart School of Industrial and Systems Engineering, to study the attrition of students admitted to Ph.D. programs at Georgia Tech during the period 2002-2012. According to Dey, who presented the project at the poster session, their big take-away is how little is known about the churn of Ph.D. students at Tech compared with undergrads.

Despite the limited data, the study showed clear differences in rates of Ph.D. completion between men and women and among racial groups. The gaps varied across Georgia Tech schools. The hope, Dey said, is to discover the practices of the schools with high rates of Ph.D. graduation across the board so that they can be shared with other units that are not doing so well.     

Meanwhile, Sayani teamed up with Jerrold Mobley, public services associate in the Georgia Tech library, and Michelle Gaines, a former postdoctoral researcher in the School of Chemical and Biomolecular Engineering and now an assistant professor of chemistry and biochemistry at Spelman College. Their project, called Culture Xchange, focuses on person-to-person engagement as a means to tear down barriers, said Mobley, who discussed the work at the Nov. 15 poster session.

With the help of 10 volunteers, they are testing the idea. Through structured discussions, collaborative exercises, and paired excursions, participants share not-so-obvious aspects of their daily lives with each other. The hypothesis, Mobley said, is that “anyone who has the opportunity to engage in real one-on-one interactions with any person of any cultural identity, race, creed, etc., has no choice but to respect who that person is and eliminate any biases that they might have had before.”

“Inclusive excellence is a core value of the College of Sciences,” said College of Sciences Dean and Sutherland Chair Paul M. Goldbart. “I am delighted to see so many members of our college community answering the call for grassroots initiatives to promote and strengthen this core value.” 

For More Information Contact

maureen.rouhi@cos.gatech.edu

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

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