When dehydration strikes, part of the brain can swell, neural signaling can intensify, and doing monotonous tasks can get harder.

With the help of brain scans and a simple, repetitive task to test responsiveness, exercise physiologists at the Georgia Institute of Technology studied volunteer subjects who sweated a lot and did not hydrate. The fluid loss led most of the subjects to make more goofs on the task, and areas of participants’ brains showed conspicuous changes.

The researchers also found that even without dehydration, exertion and heat put a dent in test subjects’ performance, but water loss made the dent about twice as deep.

“We wanted to tease out whether exercise and heat stress alone have an impact on your cognitive function and study the effect of dehydration on top of that,” said Mindy Millard-Stafford, the study’s principal investigator and a professor in Georgia Tech’s School of Biological Sciences. “We found a two-step decline.”

Heat, strain, accident

The researchers hope that someday this kind of research will offer insights into how increased cognitive slipups in hot settings with strenuous labor and poor hydration may endanger occupational safety, especially around heavy machines or military hardware. The fuzzed cognition could also contribute to reduced performance in competitive sports.

“When I was just getting interested in this subject, my brother was doing an internship at a steel plant, where I visited him, and it was extremely hot,” said the study’s first author Matt Wittbrodt, a former graduate research assistant at Georgia Tech. “In addition, everyone had on layers of protective clothing. We want to figure out if we can help prevent accidents in those environments.”

Millard-Stafford and Wittbrodt, who is now a postdoctoral researcher at Emory University, published their study on Thursday, August 23, in the journal Physiological Reports. Their research was partly funded by The American College of Sports Medicine Foundation.

Brain ventricles expand

In the experiments, when participants exercised, sweated and drank water, fluid-filled spaces called ventricles in the center of their brains contracted. But with exertion plus dehydration, the ventricles did the opposite; they expanded.

Functional magnetic resonance imaging (fMRI) revealed the differences. Oddly, the ventricle expansion in dehydrated test subjects may not have had much to do with their deeper slumps in task performance.

“The structural changes were remarkably consistent across individuals,” said Millard-Stafford a past president of The American College of Sports Medicine. “But performance differences in the tasks could not be explained by changes in the size of those brain areas.”

Changes in neural firing patterns showed up during dehydration, too.

“The areas in the brain required for doing the task appeared to activate more intensely than before, and also, areas lit up that were not necessarily involved in completing the task,” Wittbrodt said. “We think the latter may be in response to the physiological state: the body signaling, ‘I’m dehydrated’.” 

Mind-numbing task

The task the subjects completed was mindless and repetitive.

For 20 straight minutes, they were expected to punch a button every time a yellow square appeared on a monitor. Sometimes the square appeared in a regular pattern, and sometimes it appeared randomly. The task was dull for a reason.

“It helped us to avoid the cognitive complexity behind elaborate tasks and strip cognition down to simple motor output,” Wittbrodt said. “It was designed to hit essential neural processing one would use to make straightforward, repetitive movements.”

Past studies have indicated that this kind of task reflects the neural processing involved in real-life motor functioning, especially in the repetition common in manual labor or military exercises. Such monotony can foster attention lapses that heat, strain, and fluid loss may exacerbate. 

Sweating for science

Thirteen volunteers performed the task on three separate occasions:

• Once after just relaxing and staying hydrated.
• Once after extended heat, exertion, and sweat but with drinking water during exercise.
• And once with heat, exertion, and sweat but without drinking water.

Even after just relaxing, task performance gradually slipped as the 20 minutes crept by. But under the subsequent stressors, average overall performance ratcheted down. A few of the volunteers did perform the task stalwartly under all imposed conditions.

The subjects completed the task in air-conditioned rooms and after a break from strenuous activity. In a real-world scenario, in which heat and toil are unrelenting, performance may collapse even further.

Overhydration also bad 

Going forward, the researchers would like to know if hydrating with electrolyte drinks might mitigate performance slumps even better than water did.

“Blood plasma gets diluted with water replacement alone,” Millard-Stafford said. “If blood sodium -- plain old salt -- drops too much while water in the blood increases too much, that’s dangerous. It’s a condition known as water intoxication or hyponatremia.”

Ultra-endurance athletes who end up in the medical tent are sometimes suffering from dehydration but also sometimes from water intoxication. Just the right balance of water seems to be important for the brain.

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Also READ: As We Get Parched, Cognition Can Sputter

Georgia Tech’s Michael Sawka and Lewis Wheaton, and J. C. Mizelle of East Carolina University contributed to this study. Research was partly funded by The American College of Sports Medicine Foundation’s C. V. Gisolfi Doctoral Student Research Grant. 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 American College of Sports Medicine.

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Brian Hammer and Joel Kostka have been named American Society for Microbiology (ASM) Distinguished Lecturers. Hammer is an associate professor in the School of Biological Sciences. Kostka has joint appointments in the School of Biological Sciences and the School of Earth and Atmospheric Sciences. Both are members of the Parker H. Petit Institute for Bioengineering and Bioscience.

Hammer and Kostka are two of the eight ASM Distinguished Lecturers recently named to serve until 2020. Selection is based on a competitive process. Only the most distinguished individuals are named to the ASM Distinguished Lecturer Program.

The two microbiologists study microbe-microbe microbe-host interactions important in humans and in ecosystem health. Georgia Tech is emerging as a leader in this burgeoning research area. 

As distinguished lecturers, Hammer and Kostka will speak at ASM branch meetings throughout the U.S. Their visits to various parts of the country will provide opportunities for students and early-career research microbiologists to interact with prominent scientists.

A Passion for Training Young Researchers
Hammer's research aims to understand the mechanisms bacteria use to cooperate and compete in niches they occupy. His work focuses on the waterborne microbe Vibrio cholerae, which causes outbreaks of cholera disease in places like Yemen where people have no option but to consume contaminated water.

His lab has identified components of regulatory networks in this bacterium that control secreted enzymes, biofilm matrix material, a molecular harpoon for toxifying neighboring cells, and an apparatus to take up foreign DNA.

Next, his lab aims to identify new genes and regulatory connections of these networks, characterize the behaviors they control, and determine the contribution of these activities to the fitness and adaptability of this waterborne microbe in host and ecological settings.

“I enjoy the challenge and excitement of engaging students and postdocs in conversations – about my lab’s research, about microbiology, and about being a research scientist,” Hammer says. “My passion for training young researchers stems from the mentoring I received from my own advisors, who are extraordinary scientists and communicators. As an ASM Distinguished Lecturer, I will relish the opportunity to serve as a model for students and postdocs discovering their unique career paths.

On the lecture circuit, Hammer will be talking about the following topics:

• Control of Bacterial Biofilms by Quorum Sensing Small RNAs  
• Natural Transformation in Vibrio cholerae  
• Type VI Secretion Alters the Organization of Bacterial Communities  
• Carving Out Your Niche (in Microbiology)  

On a Mission to Catalyze Students
Kostka is well-known for his research in environmental microbiology. His lab characterizes the role of microorganisms in the functioning of ecosystems, especially in the context of bioremediation and climate change. He is co-principal investigator of C-IMAGE-III. This consortium is funded by the Gulf of Mexico Research Initiative to study the environmental consequences of the release of petroleum hydrocarbons on living marine resources and ecosystem health.

“I was first introduced to ASM by attending a branch meeting in Gatlinburg, Tennessee, while I was a master’s student. My experience there was largely responsible for my decision to enter the field of environmental microbiology,” Kostka says. “I wanted to participate in the ASM Distinguished Lecturer Program so that I can give back the support and encouragement that I received at many ASM meetings. I very much believe that it is my professional mission to excite students about the myriad ways that microbes benefit society, thereby catalyzing their entrance into the field.” 

On the lecture circuit, Kostka will be discussing the following:

• A Moveable Feast: The Response of Benthic Microbes to the Deepwater Horizon Oil Well Blowout in the Gulf of Mexico
• The Sphagnum Phytobiome: A Team of Ecosystem Engineers in Resource Limited Peatlands  
• Can Peat Beat the Heat?: Stability of the Peatland Carbon Bank to Deep Warming  
• New Pathways of Organic Matter Decomposition Limit Methane Emission from Wetland Soils  
• Biogeography of Benthic Microbial Communities in the Gulf of Mexico  

A car accident leaves an aging patient with severe muscle injuries that won’t heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method may help change this.

Researchers at the Georgia Institute of Technology engineered a molecular matrix, a hydrogel, to deliver muscle stem cells called muscle satellite cells (MuSCs) directly to injured muscle tissue in patients whose muscles don’t regenerate well. In lab experiments on mice, the hydrogel successfully delivered MuSCs to injured, aged muscle tissue to boost the healing process while protecting the stem cells from harsh immune reactions.

The method was also successful in mice with a muscle tissue deficiency that emulated Duchene muscular dystrophy, and if research progresses, the new hydrogel therapy could one day save the lives of people suffering from the disease.

Inflammatory war zone

Simply injecting additional muscle satellite cells into damaged, inflamed tissue has proven inefficient, in part because the stem cells encounter an immune system on the warpath.

“Any muscle injury is going to attract immune cells. Typically, this would help muscle stem cells repair damage. But in aged or dystrophic muscles, immune cells lead to the release a lot of toxic chemicals like cytokines and free radicals that kill the new stem cells,” said Young Jang, an assistant professor in Georgia Tech’s School of Biological Sciences and one of the study’s principal investigators.

Only between 1 and 20 percent of injected MuSCs make it to damaged tissue, and those that do, arrive there weakened. Also, some tissue damage makes any injection unfeasible, thus the need for new delivery strategies. 

“Our new hydrogel protects the stem cells, which multiply and thrive inside the matrix. The gel is applied to injured muscle, and the cells engraft onto the tissues and help them heal,” said Woojin Han, a postdoctoral researcher in Georgia Tech’s School of Mechanical Engineering and the paper’s first author.

Han, Jang and Andres Garcia, the study’s other principal investigator, published their results on August 15, 2018, in the journal Science Advances. The National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health funded the research.

Hydrogel: watery nets

Hydrogels often start out as water-based solutions of molecular components that resemble crosses, and other components that make the ends of the crosses attach to each other. When the components come together, they fuse into molecular nets suspended in water, resulting in a material with the consistency of a gel. 

If stem cells or a drug are mixed into the solution, when the net, or matrix, forms, it ensnares the treatment for delivery and protects the payload from death or dissipation in the body. Researchers can easily and reliably synthesize hydrogels and also custom-engineer them by tweaking their components, as the Georgia Tech researchers did in this hydrogel. 

“It physically traps the muscle satellite cells in a net, but the cells also grab onto chemical latches we engineered into the net,” Han said.

This hydrogel’s added latches, which bond with proteins protruding from stem cells’ membranes, not only increase the cells’ adhesion to the net but also hinder them from committing suicide. Stem cells tend to kill themselves when they’re detached and free-floating. 

The chemical components and the cells are mixed in solution then applied to the injured muscle, where the mixture sets to a matrix-gel patch that glues the stem cells in place. The gel is biocompatible and biodegradable.

“The stem cells keep multiplying and thriving in the gel after it is applied,” Jang said. “Then the hydrogel degrades and leaves behind the cells engrafted onto muscle tissue the way natural stem cells usually would be.”

Stem cell breakdown

In younger, healthier patients, muscle satellite cells are part of the natural healing mechanism.

“Muscle satellite cells are resident stem cells in your skeletal muscles. They live on muscle strands like specks, and they’re key players in making new muscle tissue,” Han said.

“As we age, we lose muscle mass, and the number of satellite cells also decreases. The ones that are left get weaker. It’s a double whammy,” Jang said. “At a very advanced age, a patient stops regenerating muscle altogether.”

“With this system we engineered, we think we can introduce donor cells to enhance the repair mechanism in injured older patients,” Han said. “We also want to get this to work in patients with Duchene muscular dystrophy.”

“Duchene muscular dystrophy is surprisingly frequent,” Jang said. “About 1 in 3,500 boys get it. They eventually get respiratory defects that lead to death, so we hope to be able to use this to rebuild their diaphragm muscles.”

If the method goes to clinical trials, researchers will likely have to work around the potential for donor cell rejection in human patients.

Also READ: Punching Cancer with RNA Knuckles Wrapped in Hydrogel

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The following researchers coauthored the paper: Shannon Anderson, Mahir Mohiuddin, Shadi Nakhai, and Eunjung Shin from Georgia Tech; Isabel Freitas Amaral, and Ana Paula Pêgo from the University of Porto in Portugal, and Daniela Barros from Georgia Tech and the University of Porto. The research was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (awards # R21AR072287 and R01AR062368). Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect views of the National Institutes of Health.

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Aug. 21, 2017, the first day of the school year: At noon the Georgia Tech campus morphs into a massive, festive solar-eclipse-watching party. Thousands sprawl on Tech Green and stand on roof tops to cheer the celestial event.

Meanwhile in Kentucky, James Boehm is part of an experiment by AT&T. The company is testing a device to enable Boehm – who has been blind since he was 13 – to experience the eclipse. The set-up includes a soundtrack, which “voices” the changes in temperature and brightness as the moon’s shadow covers the sun. That accompaniment came from researchers in the Georgia Tech Sonification Lab.

That story leads the first season of the College of Sciences’ podcast. The people who made the 2017 eclipse-watching party possible now offer another treat: ScienceMatters, a podcast celebrating discoveries and achievements – the “Wow” and “Aha” moments – of Georgia Tech scientists and mathematicians.

Season 1 is now available at sciencematters.gatech.edu. 

Continue here for the full story.

Editor's Note: This story by Victor Rogers was originally published on the Georgia Tech News Center on Aug. 8, 2018.

When Will Ratcliff and Peter Yunker first met for coffee they had no idea they would eventually collaborate on research that would be published in Nature Communications and Nature Physics.

Ratcliff, an assistant professor in the School of Biological Sciences, arrived at Tech in January 2014. Yunker, an assistant professor in the School of Physics, arrived in January of the following year.

“I met with [Physics Professor] Dan Goldman and told him about my interests in biophysics,” said Yunker. “He told me there’s another young guy who just arrived. You should contact him.”  

Yunker reached out to Ratcliff, and the two began meeting weekly for coffee in the basement of the College of Computing.

“I think our conversations for a solid six months were just about friend stuff,” Ratcliff said. “We talked about science, but we weren’t actively pursuing projects. We were just hanging out and getting to know each other.”

Yunker said they discussed ideas about the evolution of multicellularity.

“Will would talk a little about the biology of the evolution of multicellularity. And then we would pivot, and I would talk about the physics of multicellularity,” Yunker said. 

Though coming from different disciplines — biology and physics — Ratcliff and Yunker quickly recognized some common ground.  

“I would say, ‘There’s this thing in biology where this needs to happen,’ and he would say ‘there’s this thing in physics where this needs to happen,’” Ratcliff said. “It would blow my mind because it was a totally different way of thinking about the things that I was already thinking about. It was incredibly exciting because there were these parallels coming from such different places, and they were describing the same overlapping material. I think we both could tell there was a lot of cool stuff to be done.”

The harder part was figuring out where the overlap was concrete so they could actually conduct experiments or write models.

“A lot of our conversations are brainstorming style,” Yunker said. “They’re less about knocking down ideas and more about: ‘Let’s get a lot of information out there so we can find where that concrete idea emerges.’”  

The collaboration also eased the pressure of being a new faculty member.

“It’s nice to work with other people who are at a similar level, to bounce ideas off each other, talk about critical review, and vent about frustrations,” Yunker said. “The whole time I’ve been here I have always heard Georgia Tech is very supportive of collaboration. I’ve heard of other places where that support isn’t there when you’re still at the assistant professor level. I haven’t worried at all about if there will be trouble down the line if we collaborate. Instead, I see it as we’re doing the best science, and that’s what Georgia Tech wants.”

Ratcliff said, “That’s one of Georgia Tech’s real strengths. People really appreciate our collaboration. I hear from people in both communities — biology and physics. They appreciate not just the research, but also the strengthening of the bridge between the departments and the sense of community it builds.”

In addition to their research collaborations, Ratcliff and Yunker co-advise a Ph.D. student and a postdoc.

Collaboration Advice to New Faculty

Yunker and Ratcliff make collaboration look deceptively easy.

“Collaboration takes effort. It takes sustained interaction,” Ratcliff said. “There’s got to be a reason to do that because as new professors we’re super busy trying to get everything off the ground: get your lab running, get grants, write papers, design classes, do service work. We’re spread really thin. So, to have sustained interactions that are needed for a good collaboration, you have to prioritize it and want to do it.”

Yunker added, “One of the best approaches when starting a new collaboration is to either let it grow or die on its own. If the idea isn’t there or if you just don’t mesh, then forcing it is going to be difficult for everyone.”

Ratcliff has advice for new faculty who are interested in collaborating.

“It’s really exciting and valuable to have a close collaborator from a different discipline or with a  different skillset,” he said. “To get that, I suggest forming collaborations with other professors who are about your age. Key reasons are you’re both at the same stage in your careers. You’re equals. Also, a new professor is likely to have time to form new collaborations. Lastly, new professors have startup funds and a large degree of flexibility. This is great for trying things that are risky.”

He also suggests attending receptions for new faculty.

“Talk to people outside of your discipline. Don’t spend all of your time at the mixer talking to your departmental colleagues,” Ratcliff said.

Developing a good collaboration can be transformational.

“Our collaboration has fundamentally reshaped the way I think about key problems in my field,” Ratcliff said. “I know how to think about the things I was trained to think about, but I had no idea how to think about things I wasn’t trained to think about.”

Yunker said, “Together we’re able to ask and answer more interesting questions. I was not versed at all on questions about evolutionary transitions and individuality. I wasn’t aware of all the open questions and problems there, and they’re fascinating. By coming together, we end up asking even more interesting questions and, hopefully, coming up with new approaches.”

Ratcliff said what made the collaboration work is that he and Yunker became friends.

“We enjoy hanging out. I look forward to having coffee,” Ratcliff said. “We have these exciting scientific discussions where it was obvious that there’s something there, but we had to make the ideas touch down to reality.”

Editor’s Note: This story was written by Emily Woodward, public relations coordinator for Marine Extension and Georgia Sea Grant. It was originally published in the UGA Marine Extension and Georgia Sea Grant Newsletter Volume 4, issue 5.

Four coolers, two shovels, countless sampling vials and five people pile into a vehicle headed to a secluded salt marsh on Sapelo Island, Georgia. It’s a surprising amount of equipment needed to study the microscopic community of organisms responsible for the health of Georgia’s most abundant coastal habitat, the salt marsh.   

“Plant microbiome research, I always say, is about 10 years behind human microbiome research,” says Joel Kostka, jointly appointed professor of biology and earth and atmospheric sciences at Georgia Institute of Technology.

Roughly half of the cells in the human body are microbial. These microbes, mostly bacteria, all have different functions; some make us ill, but most keep us healthy by helping with digestion or preventing infection. Together, these microorganisms make up the human microbiome.

The same is true in the plant world, though little is known about plant microbiomes, particularly those associated with salt-tolerant coastal plants like Spartina alterniflora, which dominate Georgia’s salt marshes.  

With funding from Georgia Sea Grant, Kostka is studying the microbes intimately associated with Spartina to better understand how the plant microbiome supports the health of Georgia’s salt marshes.

“In a way, this is discovery-based science because no one has studied the microbes that are intimately associated with these plants,” says Kostka. “When you look at the marsh from a large scale it really looks constant and consistent, but when you get down at the micro level you see all kinds of differences. There's a lot of complexity there.”

The research team wants to know how the microbial community changes as you move from the interior of the marsh, where the growth of Spartina is stunted and the plants are short, to the taller, lush marsh growing near the tidal creeks.

At the site, they measure salinity, oxygen, and pH as well as the height and density of Spartina at different spots along a transect. A hole punch is used to collect samples of Spartina blades, which will be measured for nutrients, like phosphorous and nitrogen. Soil samples and root material are taken back to the lab where the latest gene sequencing and metagenomics methods will be used to identify individual microbes and understand the microbial processes that improve the health of the plant. 

“We have a number of parameters that we can measure to determine whether the plants are healthy, and then we go in and look at the microbes in more healthy plants versus less healthy plants, and see how those microbes are changing,” says Kostka.

It’s a lot of data to collect and the work isn’t easy, especially when trudging through knee-high marsh mud in 90-degree temperatures.

Luckily, Kostka has an extra set of hands to help with the sampling.

Elisabeth Pinion, an AP environmental science teacher from Cumming, Georgia, is working alongside Kostka and his team. Pinion is one of 16 educators participating in Schoolyard Program of the NSF-supported Georgia Coastal Ecosystems (GCE) Long Term Ecological Research (LTER) Project, which is hosted every summer at the University of Georgia Marine Institute on Sapelo Island. As part of the program, teachers spend a week on the coast, shadowing different researchers in the field and learning about sampling methods and processes that can be taken back to the classroom.

Pinion recognized similarities between the topics she covers in class and the research methods used for this project.

“Studying parameters that determine the productivity of different ecosystems is something that we generally spend a lot of time on,” says Pinion. “What they are looking at is very applicable to the classroom.”

Throughout the week, Kostka will have the opportunity to engage multiple educators in the field, showing him or her how they collect samples for microbiology and discussing the important ecosystem services that salt marshes provide.

"The Schoolyard Program is a great way to give the teachers a behind-the-scenes look at how science is conducted, including sometimes having to rethink your strategy once you get out in the field," said Merryl Alber, professor of marine sciences at UGA and lead PI of the GCE LTER project. "It’s also beneficial for researchers, who have a chance to interact with the teachers and think creatively about how to bring the science back into the classroom.”

Kostka recognizes the importance of making his research accessible to educators and students, which is why he used a portion of his Georgia Sea Grant funding to support three of the educators participating in the Schoolyard Program.

The trip to Sapelo is the first of many trips the research team will make to the coast. They plan to sample sites at two other barrier islands; Tybee Island and St. Simons Island, in the coming months.

Kostka hopes results from the project can be used to develop innovative methods for improving salt marsh restoration practices in Georgia. One example would be to create plant probiotics that could be applied to Spartina seedlings when planting new marshes.

“We could grow beneficial microbes in the lab and add them to the naked roots during planting, which would help the plant to take hold in the intertidal zone,” says Kostka.

“With sea level rise and increased coastal development, restoration activities will be more important to maintaining the productivity of Georgia’s marshes,” says Mark Risse, director of Marine Extension and Georgia Sea Grant.  

“Funding research like this, that helps us improve attempts to establish native vegetation, will inform future restoration projects and hopefully make them more economically and environmentally efficient.”

A tidal-energy harvester inspired by the human heart. A soil-erosion solution that mimics a kingfisher’s eyelid. A mosquito-control device that functions like carnivorous plants. These technologies are among the eight finalists in a global competition that asks innovators to create radically sustainable climate-change solutions inspired by the natural world.

Among the finalists is Team FullCircle,  a multidisciplinary team from Georgia Institute of Technology. The team wanted to find a more resilient way to harvest renewable energy, so they created a nature-inspired energy generator that produces clean renewable electricity from underwater sea currents.

The design was informed by the bell-shaped body of jellyfish, how schools of fish position themselves, how heart valves move liquid, and how kelp blades adapt rapidly to flowing water to maximize photosynthesis. Their goal is to create a more efficient way to generate power, decrease cost, and make this approach available to areas vulnerable to electricity shortage.

Members of Team FullCircle are students from the College of Sciences and College of Engineering:

• Ananya Jain, research leader, School of Materials Science and Engineering (MSE)
• Kenji Bomar, School of Physics
• Heyinn Rho, MSE
• Anmbus Iqbal, School of Mechanical Engineering
• Sara Thomas Mathew, School of Mathematics
• José Andrade, School of Aerospace Engineering
• Savannah Berry, School of Biological Sciences

School of Biological Sciences Professor Jeannette Yen served as primary faculty mentor.  Yen is also director of the Center for Biologically Inspired Design at Georgia Tech. MSE Professors Preet Singh and Zhong Lin Wang also served as official research mentors. In addition, the team had access to second and third lines of researchers, graduate student advisors, and investors.

The team acknowledges the assistance, guidance, and support of various units of Georgia Tech, including:

• CREATE-X at Georgia Tech  
• Georgia Tech Library
• Georgia Tech Communication Center (CommLab)
• Georgia Tech LMC CoLab
• Materials Innovation & Learning Laboratory (MILL)
• Scheller College of Business
• School of Aerospace Engineering
• School of Materials Science and Engineering
• School of Mechanical Engineering

Over 60 teams from 16 countries entered the Biomimicry Global Design Challenge, submitting nature-inspired inventions to reverse, mitigate, or adapt to climate change. Finalist teams – four from the U.S. and one each from the Netherlands, Taiwan, Israel, and China – receive cash prizes and an invitation to the 2018-19 Biomimicry Launchpad, an accelerator that supports the path to commercialization. They will compete for the $100,000 Ray C. Anderson Foundation Ray of Hope Prize®.

Read more about the winners and their innovations here.

Watch Team FullCircle describe its proposal here.

“I am so, so, so thrilled!” Yen says. “I can't wait to see what happens next.”

According to Jain, the team will coordinate the engineering project and assemble a prototype remotely, from different parts of the world – India, Japan, Pakistan, Spain, and the U.S. “We have a great challenge to be working from different time zones and schedules,” Jain says. “But we will do our very best and work even harder moving forward.”

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.”

• SAPH-ire Helps Scientists Prioritize Protein Modification Research

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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Writer: John Toon

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.”

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.