Jeffrey Skolnick and coworkers at the Georgia Tech School of Biology have shown that the ability to catalyze biochemical reactions is an intrinsic property of protein molecules, defined only by their structure and the principles of chemistry and physics. Their study was published on Feb. 23, 2016, in the open-access journal F1000Research.
The finding suggests that where proteins exist, life is possible because biochemical transformations are possible. And because biochemical transformations are required for life, life as we know it could be ubiquitous in the universe.
Life on Earth depends on myriad biochemical reactions mediated by proteins. The conventional wisdom is that the biochemical properties of proteins arise from evolutionary selection. According to the new study, evolution is not necessary for the existence of proteins’ biochemical functions, although evolutionary selection may have optimized proteins for specific roles.
The study’s conclusion is profound, said Terry Snell, chair of the School of Biology, in the College of Sciences. That’s because “the impression of design pervades biology,” he explained. “All the exquisite structures in biology—such as the complex anatomy of the vertebrate eye or the molecular structure of enzymes—are thought to have arisen by adaptation directed by natural selection. The new paper suggests that a considerable portion of the design in biology can be attributed to physical and chemical laws that dictate the function and structure of proteins.”
Ron Elber concurs. He is the W.A. “Tex” Moncrief Chair in Computational Life Sciences and Biology at the University of Texas at Austin. The work “suggests that physical principles assist nature in selecting proteins for specific functions,” he said. “While selection is necessary, it is useful to reduce the number of possibilities, and the Skolnick study suggests a mechanism of how that might happen.”
Skolnick and coworkers Mu Gao and Hongyi Zhou at the Center for the Study of Systems Biology studied the properties of a library of artificially generated proteins selected only for their intrinsic stability, not any type of function. They found that a remarkable number of the artificial proteins have the unique features of functional proteins, including binding pockets to accommodate small molecules. These pockets are necessary for biochemical catalysis to take place.
Although Skolnick and coworkers studied only a small ensemble of protein-like molecules, Elber observed, “it nevertheless includes features that resemble active sites even though it was generated on the basis of physical principles only.”
The researchers further predicted computationally that some members of the artificial, nonfunctional protein library would have strong protein-protein and protein-DNA interactions. Such interactions are essential in the machinery of life as we know it.
“The biochemical seeds of life could be prevalent,” Skolnick said. “If you rain meteorites containing amino acids and somehow these polymerize to form small proteins, then a subset of these would fold to stable structure and a small subset of these could engage in rudimentary metabolism, all without any selection for biochemical function. Thus, the background probability for function is much larger than had been previously appreciated.”
In a manuscript in preparation, Skolnick and coworkers have built on this finding to propose a mechanism for the emergence of chirality in biology. Many compounds can have the same structure and physical properties but differ only in their right- or left-handed orientation. In the presence of other biological molecules, such as proteins, usually only the compounds with one type of handedness—or chirality—can react. In nature, one type of handedness prevails. And how this prevalence emerged has been the subject of years of research.
During the spring 2016 round of tenure and promotion decisions at Georgia Tech, 15 faculty members from the College of Sciences made the list.
The following were promoted to full professor:
School of Applied Physiology
School of Biology
School of Earth and Atmospheric Sciences
School of Mathematics
School of Physics
School of Psychology
The following were promoted to associate professor and awarded tenure:
School of Earth and Atmospheric Sciences
School of Mathematics
School of Physics
Joseph Sadighi, of the School of Chemistry and Biochemistry, was awarded tenure.
“On behalf of the College of Sciences community, I am pleased to offer my warmest congratulations to our most recent promotion and tenure recipients,” says Dean Paul M. Goldbart. “You, and colleagues like you, are truly pivotal to the future of mathematics and the sciences at Georgia Tech.
“The knowledge and understanding that you are creating and imparting – via your scholarship, teaching and service – are the fuel that ensures the continued rise in the appreciation of the college, across our campus, nationally and worldwide.
“I look forward with tremendous excitement to your future accomplishments as researchers, educators and builders whose vision and activities will shape and strengthen the Georgia Tech of the future.”
About 30 miles west of Atlanta lies the town of Douglasville. Described variously as “charming,” having a “small-town ambiance,” and “historic,” this town of close to 32,000 people away from the frenzy and busyness of the big city would not be an obvious site for a TEDx event. And yet for the second year in a row, TEDxDouglasville is happening, thanks to two Georgia Tech students driven by a deep sense of gratitude to their hometown: Joshua Barnett, a third-year physics major, and Mahdi Al-Husseini, a third-year biomedical engineering and public policy major.
For the two undergrads, TEDxDouglasville is a means to give back to a town and community that supported them as they began their undergraduate studies at Georgia Tech. Looking ahead to their graduation from Georgia Tech, Barnett and Al-Husseini regard TEDxDouglasville as a way to stay connected to their community of origin even as they might move farther away in search of their individual futures.
Barnett and Al-Husseini have known each other since their freshman days in Douglas County High School. “By the time we graduated, we were best friends and bound for Georgia Tech,” Barnett says. Al-Husseini masterminded the creation of TEDxDouglasville, asking Barnett to join soon after the TED license was approved. Barnett did not hesitate to take the role of co-organizer. “Both of us were deeply affected by a philosophy course we had taken in high school,” he says. “And we were convinced by the power of ideas and the impact of how ideas are conveyed.”
A big surprise of the event last year was how much younger the audience was than the organizers had expected. “A large number of high school students attended,” Barnett says. “This year we have made tickets more accessible to these students, and we’re even holding the event in a school that many of them attend.”
That would be Douglas County High School. When TEDxDouglasville 2016 is held there on April 9, two College of Sciences faculty members will speak:
Brian Hammer, from the School of Biology, will talk about cooperation and conflict in the microbial world. “Microbes are ubiquitous on Earth and interact with one another and their surroundings in diverse associations that maintain the health of our planet and all of its inhabitants,” Hammer says. His research is helping to explain how bacteria cooperate and compete. And he hopes the knowledge “will allow us to monitor and manipulate these behaviors to prevent and treat human diseases and to mitigate perturbations to global ecological systems.”
Laura Cadonati, from the School of Physics, will describe the discovery of gravitational waves. “Gravitational waves are ripples in the fabric of space and time that are produced by cataclysmic astrophysical events,” Cadonati explains. One hundred years after Albert Einstein predicted their existence, one such wave was detected for the first time on Sept. 14, 2015; the wave came from the merging of two gigantic black holes 1.3 billion years ago. Cadonati will explain how gravitational waves open a new way to probe the universe.
“Events like TEDxDouglasville speak to Georgia Tech’s and the College of Sciences’ tradition of educating and nurturing the whole person and not just the engineering or the physics aspects,” says College of Sciences Dean Paul M. Goldbart. “They also underscore the College’s commitment to sharing with nonscientists everywhere the excitement and promise of our researchers’ breakthrough discoveries.”
With an average age of 21, Barnett, Al-Husseini, and the organizing team of TEDxDouglasville are on a steep learning curve to achieve their aspirations for TEDxDouglasville. Following are edited excerpts from a Q&A conducted by e-mail. Responses are from both Barnett and Al-Husseini except where indicated.
Why is Douglasville a good venue for a TEDx program?
It’s hard to resist Douglasville’s southern charm, incredible past, beautiful parks, and strength of community. Douglasville is where history meets modernity. This little, big city rests on the fringes of Atlanta, but remains far enough to stay humble.
This event is a way to engage our community. It would give people a chance to meet and converse with individuals with whom they might never interact otherwise. Diverse interactions is important in the development of a wholesome, interconnected community.
Who are the people you are trying to reach with TEDxDouglasville?
Students, construction workers, teachers, businessmen, janitors, social workers, doctors, lawyers. Anyone with a sense of curiosity. We seek to get people thinking, dreaming, and achieving.
What is your measure of success for TEDxDouglasville?
Exposing our audience to different people and new ideas was one of our goals from the beginning. But we must also consider the impact on the wider community. TEDxDouglasville inspired a new level of civic engagement: It led to a proposal for the Douglas Youth Department and catalyzed the creation of a service organization, Progressive Action Towards the Health of Douglasville, a lasting legacy.
It is also great to have scientists from Georgia Tech speak to a general audience, especially to high school students. TEDxDouglasville not only gives the audience a chance to connect with scientists on a tangible, accessible level, but it also helps to steer youth who are considering majoring in the sciences by providing a realistic snapshot of what scientific research looks like on the collegiate level.
Give us a preview of TEDxDouglasville 2016.
Our theme for this year is “Laying the Tracks,” which is rooted in the city’s origins from a railroad track. TEDxDouglasville 2016 will explore the intricacies of pioneering and building in the sciences, arts, education, and business. The event is laying tracks for ideas worth spreading, in hopes of building something extraordinary.
What happens to TEDxDouglasville when you graduate from Georgia Tech?
Al-Husseini: We aim to transform TEDxDouglasville from an annual event into a continuous platform for creative thinking and community outreach. The proceeds from this year’s event will be stored in a scholarship fund dedicated to high school students in Douglas County.
I intend to spend four years on active-duty with the US Army, after a spring 2018 Georgia Tech graduation. Upon completing my service contract, I hope to attend graduate school and eventually return to Douglasville.
Barnett: I hope to take an advisory role for a successor who will come to organize the event. With plans to attend graduate school, I must commit more and more time to research and my courses. Meanwhile, we will explore various options.
In humans, cholera is among the world’s most deadly diseases, killing as many as 140,000 persons a year, according to World Health Organization statistics. But in aquatic environments far away from humans, the same bacterium attacks neighboring microbes with a toxic spear – and often steals DNA from other microorganisms to expand its own capabilities.
A new study of more than 50 samples of Vibrio cholerae isolated from both patients and the environment demonstrates the diversity and resourcefulness of the organism. In the environment, the cholera bacterium is commonly found attached to chitin, a complex sugar used by aquatic creatures such as crabs and zooplankton to form protective shells. In the wild, most strains of cholera can degrade the shells for use as food, and the new study showed how the presence of chitin can signal the bacteria – which have receptors for the material – to produce behaviors very different from those seen in human disease.
Among the cholera strains studied, less than a quarter were able to take up DNA from other sources. Almost all of the samples taken from the environment were able to kill other bacteria – a phenomenon called “bacterial dueling” – but just 14 percent of the bacterial pathogen strains isolated from humans had that capability.
“It’s a dog-eat-dog world out there even for bacteria,” said Brian Hammer, an associate professor in the School of Biology at the Georgia Institute of Technology. “Bacteria such as Vibrio cholerae sense and respond to their surroundings, and they use that information to turn on and off the genes that benefit them in the specific environments in which they find themselves.”
The research, supported by the National Science Foundation and the Gordon and Betty Moore Foundation, provides information that could lead to development of better therapeutic agents against the disease, which is found in densely-populated areas with limited sanitation and clean water. The research was done with assistance from the Centers for Disease Control and Prevention (CDC), and was reported online March 4 in the journal Applied and Environmental Microbiology.
In humans, the cholera bacteria produce a diarrheal disease that can kill untreated patients in just a few hours. The deadly effects of the disease, however, are actually caused by a virus that infects the Vibrio cholerae strains found in humans. The toxin carried by the virus helps spread the disease among humans, but cholera strains quickly lose the virus and adapt other competitive mechanisms in the environment.
To study how cholera regulates these adaptations, Georgia Tech graduate student Eryn Bernardy obtained nearly 100 samples of cholera bacteria from a variety of sources globally, including one originally isolated from a 1910 Saudi Arabian outbreak of the disease. She then studied 53 of the samples for their ability to (1) degrade chitin, (2) take up DNA from the environment, and (3) kill other bacteria by poking them with a poisoned spear.
Colonies of each strain were grown in petri plates containing chitin material. The strains able to digest the material produced a clear ring showing that they had broken down the chitin in the agar growth medium. Only three of the cholera colonies failed to degrade the chitin.
To study their ability to take up DNA, bacterial cells were grown on crab shells, then exposed to raw DNA containing a gene for antibiotic resistance. The cells were scraped off the shells and placed onto agar plates containing an antibiotic that would normally kill the bacteria. Colonies that survived showed they had taken up the genetic material.
To study their ability to compete with other bacteria, each cholera strain was placed into contact with a billion or so E. coli cells on petri plates. After a few hours in contact, the researchers counted the number of E. coli remaining. Some cholera strains were able to kill nearly all of the E. coli cells, reducing their numbers to a few hundred thousand.
“We found a very sharp difference between the clinical isolates and the environmental isolates,” Hammer said. “For example, most of the isolates that came out of patients either couldn’t kill other bacteria, or were carefully controlling that behavior. Patient isolates have a very different way of competing inside the human body. They use the virus-encoded toxin to cause the diarrheal disease and remove their competitors from the intestine.”
With help from CDC scientists, the researchers correlated the behavior of each strain with their unique DNA sequences. They also examined the strains for the presence of the toxin used to cause disease.
To deduce the rules governing the bacterium’s behavior, Hammer and his lab have been studying cholera for the last 15 years, starting with a single strain first isolated in Peru in the early 1990s. When a cholera outbreak began in Haiti after the 2010 earthquake, his lab worked with the CDC to isolate these new strains. In further study, Hammer was surprised to find that the 2010 Haitian strains were less capable than the 1991 Peruvian variety.
“We were very surprised to find that most of the Haiti strains did not behave like the one we had been studying for years,” he said. “This was a reminder to us that we needed to embrace the diversity of the organisms we’ve been studying. We thought this would be an opportune time to start looking at how diverse Vibrio cholerae really is.”
Hammer compared the diversity of the cholera strains to the diversity of humans, who increasingly receive personalized health care.
“In humans, one size doesn’t fit all for patient care,” he said. “For cholera, the behavior is personalized for each strain. Understanding this will be useful in the development of future therapeutics, and we’re hopeful that knowing how these bacteria interact with other organisms in complex communities will lead us to things that can truly benefit humans.”
In addition to those already mentioned, the study included Maryann A. Turnsek and Cheryl L. Tarr from the CDC. Georgia Tech undergraduate Sarah K. Wilson from the Hammer lab, another author on the paper, is now a Ph.D. student at the University of Wisconsin-Madison.
This material is based upon work supported by the Gordon and Betty Moore Foundation and National Science Foundation Grant No. 1149925. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation or the Moore Foundation.
CITATION: Eryn E. Bernardy, et al., “Diversity of Clinical and Environmental Isolates of Vibrio cholerae in Natural Transformation and Contact-Dependent Bacterial Killing Indicative of Type VI Secretion System Activity,” (Applied and Environmental Microbiology, 2016). http://dx.doi.org/10.1128/AEM.00351-16.
Research News
Georgia Institute of Technology
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Writer: John Toon
Effective on July 1, 2016, the Georgia Tech College of Sciences has a new unit focused on the life sciences – the School of Biological Sciences. Emerging from a reorganization of the former Schools of Applied Physiology and of Biology, the new unit reduces the number of College of Sciences academic schools to six: Biological Sciences, Chemistry and Biochemistry, Earth and Atmospheric Sciences, Mathematics, Physics, and Psychology.
For the period immediately following the transition, the current chair of the School of Biology, Professor Terry W. Snell, will serve as the chair of the School of Biological Sciences. From August 15, 2016, the school will be led by Professor J. Todd Streelman, who currently serves as Associate Chair for Graduate Studies in the School of Biology.
The reorganization was motivated by the College’s strategic goals to enhance the research ecosystem for the basic sciences and mathematics, enrich and diversify educational opportunities for science and mathematics majors, and strengthen the opportunities for creativity and innovation by the College.
“The life sciences are an exciting and fast moving field, and the issues it addresses are varied but interconnected. It is about the systems that make life possible,” said Rafael L. Bras, provost and executive vice president for Academic Affairs. “The new School of Biological Sciences brings together individuals that span the various aspects of living systems and their study. It will add synergies and create a resilient, flexible, and fast-responding academic unit in a fast-moving field.”
A single school focused on the life sciences offers many advantages:
- A unified voice to lead conversations about the life sciences within campus
- A focal point for interactions with life science groups, program, activities, and interests outside campus
- A broader base upon which to build research teams to address complex biomedical challenges
- A robust ability to advance new health-related majors in neuroscience, physiology, and human systems
- A unique opportunity to develop an undergraduate degree for pre-health students
The new school comprises 10 tenure-track faculty, three academic professionals, and four staff from Applied Physiology and 38 tenure-track faculty, six academic professionals, and 18 staff from Biology. The School of Biological Sciences will administer all the academic programs offered previously by the two schools it replaces.
“The life sciences, including neural systems, are destined to grow and become even more central as we define our research and education programs for the new millennium,” said Paul M. Goldbart, Dean of the College of Sciences. “I am grateful to the many members of our community who have stepped up to create a stronger, more coherent base from which to take on exciting challenges presented by the life sciences.”
College of Sciences Dean Paul M. Goldbart has appointed J. Todd Streelman to serve as the chair of the School of Biological Sciences, effective August 15, 2016. The School of Biological Sciences is a new unit within the College of Sciences, effective July 1, 2016.
A professor and associate chair for graduate studies in the School of Biology, Streelman joined Georgia Tech in 2004. Previously, he did research at the University of New Hampshire, where he was the recipient of an Alfred P. Sloan Foundation Postdoctoral Fellowship in Molecular Evolution. Since joining Georgia Tech, he has been honored as a Sloan Foundation Research Fellow in Computational and Evolutionary Molecular Biology and with a National Science Foundation CAREER Award.
Streelman’s research is focused on the relationship between genotype and phenotype in wild vertebrates, often via studies of cichlid fishes from Lake Malawi, in Africa. Major themes include aspects of the genomic and cellular circuitry of complex behavior, tooth and taste bud patterning and regeneration, and developmental diversification of the brain. Streelman served as associate editor for the journal Evolution and is a standing member of the National Institutes of Health Study Section on Skeletal Biology Development and Disease.
For the past four years, Streelman has played a pivotal role in defining the research themes for the Engineered Biosystems Building I, Georgia Tech’s inspiring new venture to catalyze interactions between life scientists and life engineers. He also co-chairs an Institute task force charged with developing Georgia Tech’s strengths in the field of neuroscience.
“My colleagues in the College of Sciences team and I are excited to be partnering with Todd and our colleagues in the School of Biological Sciences,” says College of Sciences Dean Paul M. Goldbart.
The new School of Biological Sciences combines the Schools of Applied Physiology and of Biology. The single entity is designed to capitalize on and add coherence to Georgia Tech’s broad strengths in the life sciences, both in research and in the suite of educational opportunities that the school will offer.
In taking on the role of chair, Streelman will be building on the outstanding leadership of Professors T. Richard Nichols and Terry W. Snell, says Dean Goldbart. “Richard and Terry have led their respective schools, Applied Physiology and Biology, with distinction, and they have guided the fusion of the schools with sensitivity and vision. I thank them for their critically important contributions.”
“I am thrilled to be named chair, on behalf of my colleagues in the School of Biological Sciences,” Streelman says. “I am excited to continue progress made under Richard and Terry, to both sustain and propel innovative research and teaching in the life sciences.”
Streelman’s appointment follows a national search conducted by Georgia Tech faculty members Linda E. Green, Brian K. Hammer, Julia Kubanek, Garrett B. Stanley, Joshua S. Weitz, Loren D. Williams, and Soojin Yi. Leading the search committee was Hang Lu, of Georgia Tech's School of Chemical and Biomolecular Engineering.
For elementary school children, an upcoming field trip is riveting, the one time they find themselves unable to sleep in anticipation. This year, fifth-grade students at Laurel Ridge Elementary School, in Decatur, were bound for a beach on Tybee Island, the easternmost point of the state of Georgia. But some couldn’t go. Thanks to School of Biology Professor Joel E. Kostka and his students, these fifth graders did not have to miss the excitement of a year-end activity.
“We were asked by the organizer of outreach opportunities – Tracy Hammer – to come, because half of the kids in the fifth-grade class could not make it to the beach,” Kostka said. “So we brought the beach to them.”
This clever solution had many positive outcomes. It advanced Hammer’s goal for science education at Laurel Ridge. It taught Georgia Tech researchers how to explain their work to school children. And it opened the eyes of elementary students to the excitement of scientific research.
Hammer is the science, technology, engineering, and mathematics (STEM) coordinator and teacher for gifted students at Laurel Ridge. She has dedicated her career to getting young children excited about mathematics and science. “Part of my mission at school is to expose all of the kids to science in as many ways as I can,” she said. “I refused to have our fifth graders staying behind, missing out on the hands-on experience the other kids were getting. So I decided to bring science to the school.”
Kostka came with graduate students Will A. Overholt, Boryoung Shin, and Xiaoxu Sun and undergraduate biology major Kyle Sexton. At Georgia Tech, one research focus in the Kostka lab is biodegradation of oil in the oceans, including oil spills in the Gulf of Mexico. Kostka and his students study how marine microbes break down oil, how fast the breakdown occurs, and what factors affect the process. Their goal is to learn enough to direct the management and cleanup of contaminated systems, such as the aftermath of the 2010 Deepwater Horizon oil spill in the Gulf of Mexico. The beach they brought to Laurel Ridge resembled those sullied by the environmental disaster.
One of Hammer’s goals is for Laurel Ridge to be STEM certified. The process requires the school to have community and industry partners. To fulfill this requirement, Hammer has been inviting researchers from Georgia Tech, including her husband, School of Biology’s Brian K. Hammer.
According to the Georgia Department of Education, STEM-certified schools offer an integrated curriculum in STEM “that is driven by problem solving, discovery, exploratory project/problem-based learning, and student-centered development of ideas and solutions.”
To doubters, who may think such a program would be too much for elementary-level students, Tracy Hammer would disagree. “I believe we underestimate elementary school children and their abilities and interest levels when it comes to science,” she said. “The more we offer, the more they want to learn, and the more questions they ask.”
The Georgia Tech researchers engaged the fifth-graders in activities they named “Oiled Beach,” designed by Beth Kostka, wife of Joel Kostka, and a teacher Renfroe Middle School, in Decatur. Working in small groups of six to eight members per group, the school children modeled oil spills, counted bacteria, discussed Gulf of Mexico ecosystems, and watched oil-eating bacteria at work.
“The children were really engaged, had fantastic questions,” Overholt said. “They seemed to really enjoy the two hours we spent with them.”
Seeing the students’ thirst for knowledge and ability to learn was an eye-opening experience for Overholt. “The kids were so excited about things that my peers and I take for granted,” he said. “It was very rewarding to see kids so curious about the world around them. I also think it is great practice to talk about our science at the fifth-grade level and still be able to communicate what we do.”
Through these activities led by research scientists, Tracy Hammer moves closer to her goal of getting Laurel Ridge STEM-certified. “When we expose our budding scientists to the world and the possibilities it holds,” she said, “then we can say we are truly doing our jobs as educators.”
She hopes Joel Kostka will return and that other Georgia Tech research groups would visit Laurel Ridge throughout the year.
“I will do it again,” said Joel Kostka. “The kids were very perceptive. I learned that kids as young as those in fifth grade can really understand the oceans and the implications of oil spills. Those kids have a lot to offer.”
Although the “beach” they had did not come with sun and ocean and waves, the children had a great time. “When the others returned from Tybee,” Tracy Hammer said, “the kids who stayed behind were the ones bragging about their experiences.”
Scott Smith
Student Assistant, College of Sciences
Effective July 1, the Georgia Tech College of Sciences has a new unit focused on the life sciences — the School of Biological Sciences.
The new school emerged from a reorganization of the former Schools of Applied Physiology and of Biology. The reorganization was motivated by the College’s strategic goals to enhance the research ecosystem for the basic sciences and mathematics, enrich and diversify educational opportunities for science and mathematics majors, and strengthen the opportunities for creativity and innovation by the College.
“The life sciences are an exciting and fast-moving field, and the issues it addresses are varied but interconnected,” said Rafael L. Bras, provost and executive vice president for Academic Affairs. “The new School of Biological Sciences brings together individuals that span the various aspects of living systems and their study. It will add synergies and create a resilient, flexible, and fast-responding academic unit in a fast-moving field.”
J. Todd Streelman, associate chair for Graduate Studies in the School of Biology, will serve as chair of the new School beginning August 15. Terry W. Snell, professor and chair for the School of Biology, will serve as chair in an interim role until then.
“I am thrilled to be named chair on behalf of my colleagues in the School of Biological Sciences,” Streelman said. “I am excited to continue progress made under Richard [Nichols] and Terry [Snell] to both sustain and propel innovative research and teaching in the life sciences.”
The new school comprises 10 tenure-track faculty, three academic professionals, and four staff members from Applied Physiology as well as 38 tenure-track faculty, six academic professionals, and 18 staff members from Biology. The School of Biological Sciences will administer all the academic programs offered previously by the two schools it replaces.
“The life sciences, including neural systems, are destined to grow and become even more central as we define our research and education programs for the new millennium,” said Paul M. Goldbart, dean of the College of Sciences. “I am grateful to the many members of our community who have stepped up to create a stronger, more coherent base from which to take on exciting challenges presented by the life sciences.”
The other academic schools in the College of Sciences include Chemistry and Biochemistry, Earth and Atmospheric Sciences, Mathematics, Physics, and Psychology.
In tough times, humans aren’t the only species that think twice about having children. Consider roundworm strain LSJ2.
Though it can’t think – much less think twice -- about anything, the laboratory worm underwent a surprising mutation that made it prioritize the survival of adults over creating abundant offspring. Researchers noticed the sweeping change in behavior, and the mutation, after LSJ2 had faced hardship for 50 years.
Such so-called life history trade-offs have been described in many living things from mice to elephants, but now, for the first known time, researchers at the Georgia Institute of Technology have pinned some to a specific mutation.
“This is a great hint at how life history trade-offs could be regulated genetically,” said lead researcher Patrick McGrath, an assistant professor in Georgia Tech’s School of Biological Sciences.
The researchers confirmed the link in LSJ2, a strain of the C. elegans species, by duplicating the mutation in another strain, which reproduced the mutation’s effects to a very high degree.
The researchers published their results in the journal PLOS Genetics on Thursday, July 28, 2016. Their work has been funded by the National Institutes of Health and the Ellison Medical Foundation.
Snowball to avalanche
The mutation in the LSJ2 strain amounted to a small deletion in its DNA. As a result, a large protein changed by a meager 10 of its roughly 3,000 amino acids.
But that triggered a huge behavioral overhaul that boosted lifespan and slowed down reproduction. The contrast between the minor genetic tweak and its transformative ramifications might compare well with a toddler knocking loose an avalanche with a snowball.
The new discovery also has a tangential connection to human genetics. The roundworm shares with us the NURF-1 gene, on which the mutation occurred. And an associated human protein is involved in, among other things, reproduction.
Evolve faster, please
All at once, LSJ2 did a lot of peculiar things, and that got the attention of McGrath and his team. And that’s what the lab roundworms are there for.
Since 1951, generations of scientists have been speeding up the evolution of lab-bound C. elegans by forcing the microscopic species of roundworms to adapt to new, mostly stressful, conditions. Then, when researchers have noticed changes, they’ve worked to trace them to the animals’ genes.
McGrath points to a thin, glass slide standing vertically under a light with tubules of fluid connected to it. Inside the slide, is a different lab strain of C. elegans.
“We’re raising those in fluid with gravity pulling them down to see if mutations will give them the ability to swim,” McGrath said.
50 years of bread and water
In the case of LSJ2, researchers came up with a different challenge to accelerate its evolution. They fed it bland food for 50 years.
“It’s a diet of watery soy extract with some beef liver extract,” said Wen Xu, a graduate student who researches with McGrath. Sounds yucky enough to humans, but to the roundworm, it's worse. It equates to a regimen of bread and water.
Mutations eventually took hold to promote LSJ2’s survival in the scanty broth, and they were head-turning.
Fewer kids, less sleep
“The stark thing that we noticed first was the propensity to no longer enter the state called dauer,” McGrath said. It’s a kind of hyper-hibernation. “Dauer is something most C. elegans do to extend their lives, but LSJ2 did not. And it lived longer in spite of it.”
Then the list of anomalies grew, and grew.
“We found that almost everything was affected – when they started reproducing, how many offspring they made, how long they lived,” McGrath said. Some even survived exposure to drugs and heavy metals.
“Eventually we realized that the worms were prioritizing individual survival over reproductive rate.”
Mutation sleuthing
In many species, sex dries up when food is scarce, resulting in fewer progeny to compete for it. In addition, many organisms are well-equipped to manage their energies to survive dearth.
But C. elegans LSJ2 had to mutate into those abilities, and so many mutation-based behavioral changes all at once is uncommon.
“What you usually find is mutations that play narrow, very specific roles,” McGrath said. “They only affect egg laying, or they only affect life span, or they only affect dauer formation."
McGrath and Xu went sleuthing for DNA alterations by mapping quantitative trait loci, which matches up changes in characteristics to genetic changes. They dug in for a long investigation, anticipating multiple suspects among LSJ2’s many mutations.
“There were hundreds of genetic differences between roundworm strain LSJ2 and the one we were comparing it to,” McGrath said.
‘Smoking gun’
The comparison laboratory strain is called N2, and it has led a pampered existence with a diet of E. coli -- optimal food for C. elegans. (Both the E. coli and the roundworms are strains that are not harmful to humans.)
So, N2 hadn’t been pushed to mutate so much. In addition, to avoid confusion in their research results, the researchers reset some of the mutations N2 did happen to undergo.
The comparison led to swift evidence in LSJ2. “Every single time, it pointed us to the same genetic region on the right arm of chromosome 2,” McGrath said. C. elegans has six chromosomes.
“There were only five genes that were candidates. One of the mutations was a smoking gun -- a 60-base-pair deletion just at the end of the NURF-1 gene.”
NURF-1 has the function of remodeling chromatin, which pairs DNA with proteins to wrap them into chromosomes. The resulting configurations strongly influence which genes are expressed. It appears the tiny mutation in the remodeling gene may have led to a massive change in the expression of other genes.
There are missing pieces needed to understand the pathway from the mutated gene to the massive real-life changes, and the researchers are working to fill them in.
Worm whoopy
To confirm the mutation as the trigger of the changes, Xu deployed a CRISPR Cas9 gene editor into N2 worms to make the deletion that LSJ2 had received via mutation, and the results left little doubt.
“It had a lot of the same effects – longer life, dauer formation,” Xu said. “The main difference was the reduction of reproduction rates. It was only about half as much in the comparison worm that got the gene editing.”
By the way, as sex goes, C. elegans are mostly hermaphrodites that produce eggs and their own sperm to fertilize them with. But there are also males that copulate with the hermaphrodites to add new sperm and with it genetic diversity.
Edward E. Large, Yuehui Zhao and Lijiang Long from Georgia Tech; Shannon Brady and Erik Andersen from Northwestern University, and Rebecca Butcher from the University of Florida coauthored the paper. Research was sponsored by grants from the National Institutes of Health (numbers R21AG050304 and R01GM114170) and by an Ellison Medical Foundation New Scholar in Aging grant.
In ocean expanses where oxygen has vanished, newly discovered bacteria are diminishing additional life molecules. They are helping make virtual dead zones even deader.
It’s natural for bacteria to deplete nitrogen in oxygen minimum zones (OMZs), ocean regions that have no detectable O2. But as climate change progresses, OMZs are ballooning, and that nitrogen depletion is also on the rise, drawing researchers to study it and possible ramifications for the global environment.
Now, a team led by the Georgia Institute of Technology has discovered members of a highly prolific bacteria group known as SAR11 living in the world’s largest oxygen minimum zone. The team has produced unambiguous evidence that the bacteria play a major role in denitrification.
7 questions, 7 answers
The new bacteria impact global nutrient supplies and greenhouse gas cycles. Below are questions and answers that illuminate the discovery and its significance.
The researchers published their findings in the journal Nature on Wednesday, August 3, 2016. They produced genomic and enzyme analyses that pave the way for further study of carbon and nitrogen cycles in oxygen minimum zones.
The research has been funded by the National Science Foundation, the NASA Exobiology Program, the Sloan Foundation and the U.S. Department of Energy.
1. Why does denitrification matter?
While melting ice caps and dying polar bears splash across headlines, climate change is stressing oceans in other ways, too – such as warming and acidifying waters. Loss of ocean oxygen and nitrogen are pieces of that bigger puzzle.
As to nitrogen: Anyone who has picked up a bag of fertilizer knows it as a building block of life.
“It’s an essential nutrient,” said Frank Stewart, an assistant professor at Georgia Tech’s School of Biological Sciences, who headed the team. “Nitrogen is used by all cells for proteins and DNA.”
Taking it away makes it harder for algae and other organisms to grow, or even live. But it doesn’t stop there. Algae absorb carbon dioxide, so, when algae are diminished, that leaves more of that greenhouse gas in the atmosphere.
But it’s not yet clear how heavily this particular loss of CO2 absorption weighs in the global balance.
2. How do these newly discovered bacteria deplete nitrogen?
In OMZs, with O2 gone, the newly discovered strains of SAR11 bacteria (and some other bacteria) respire NO3 (nitrate) instead, the Georgia Tech researchers found. They kick off a chemical chain that leads to nitrogen disappearing out of the ocean.
“They take nitrate, convert it into nitrite (NO2), and that can ultimately be used to produce gaseous nitrogen,” Stewart said. Plain nitrogen, N2, and nitrous oxide, N2O, would result. “Both of those gases have the potential to bubble out of the system and leave the ocean.”
That makes the oxygen-barren waters even less hospitable to life while putting more nitrogen into the air, as well as nitrous oxide, a key greenhouse gas.
The newly discovered members of the SAR11 bacteria clade – clade means a branch of living species -- appear to be the single largest contingent of bacteria in OMZs. That makes them a very significant player in nitrogen loss.
3. Ocean zones with no oxygen? Sounds wild. Did climate change do that?
No. Oxygen minimum zones are natural. The issue is that global warming is making them grow, just like it’s making ice caps shrink.
OMZs form mostly in the tropics, off coastlines where wind pushes surface waters out to sea, allowing deeper waters to rise up. These are full of nutrients and boost the growth of simple aquatic life like algae.
“Eventually, the algae die and sink slowly,” Stewart said. “Bacteria munch on it, and in the process, they breathe oxygen.” There’s so much algae that the bacteria consume oxygen at a dizzying rate, depleting the water of it.
Global warming is causing OMZs to spread because it makes seawater less able to hold oxygen. As OMZs expand, so does the potential for denitrification, tipping global balances of nitrogen, greenhouse gases, and nutrients.
4. I’ve heard of the disease SARS, but what is SAR11?
The two are unrelated.
SARS is caused by a virus and is potentially deadly. SAR11 bacteria are not only harmless to humans; hypothetically, we might starve without them. They’re at the base of an oceanic food chain, which is very important to the global food supply.
“After they eat dissolved organic carbon (dead stuff), then the bacteria are eaten by bigger cells, which are eaten by larger plankton, and so on up the food chain,” Stewart said.
Previously known SAR11 are so incredibly widespread in the ocean, it’s surprising they’re not a household name. They may even comprise the largest number of living organisms on Earth.
Under the microscope, SAR11 bacteria pretty much look the same. “They’re usually short little slightly bent rods,” Stewart said. Until now, SAR11 have been known to require oxygen to live, so finding SAR11 that respire nitrate is new and surprising.
5. Where did the team get these new nitrate breathing SAR11 strains?
Stewart and his team sailed for four days aboard a research vessel from San Diego, California, to an area off the Pacific coast of Mexico’s Calimo state. There, they dropped a carousel of tube-like bottles about four feet long down to the center of the world’s largest OMZ 1,000 feet below.
“The bottoms and tops of the bottles are open,” Stewart said. “When you get to the depth you want, you close them to get your sample.”
The new bacteria don’t have species names yet, but their genomes, which were sequenced in the study, indicate they’re members of the SAR11 bacteria clade.
6. Why is this discovery scientifically significant?
It upends quite justified scientific doubts.
Scientists thought SAR11 wouldn’t have strains that flourish in the harsh OMZ environment, because the SAR11 clade doesn’t have a reputation for being very adaptable. “When their genomes do change, they’re usually very subtle changes,” Stewart said.
Many other bacteria, by contrast, plunk in and out big chunks of their DNA, making them widely adaptable. Also, though researchers had already detected genetic signatures of SAR11 bacteria in OMZs, they didn’t think the bacteria were actually at home there.
These facts put Stewart and his team under a heavy burden of proof.
7. How did the scientists answer the doubts?
They flushed out the genomes of 15 individual new bacteria strains they had captured as intact single cells. Surprisingly, the researchers found the blueprints for an enzyme, nitrate reductase, which could allow the bacteria to breathe nitrate in place of oxygen.
Since the novel bacteria have not yet been grown in the lab, the researchers inserted their nitrate reduction gene sequences into E. coli bacteria to see if they would use the DNA to produce the enzyme and if the enzyme would then work.
It did.
“Not all studies that do this kind of genome-based analysis take that extra step,” Stewart said with a long exhale. But it nailed nagging doubts.
The thorough analyses produced a critical dataset for science to build upon. More research will be needed to find out what adaptations allow SAR11 bacteria to exist under such harsh conditions.
The following researchers coauthored the study: Despina Tsementzi, Jieying Wu, Luis M. Rodriguez-R, Andrew S. Burns, Piyush Ranjan, Cory C. Padilla, Neha Sarode, Jennifer B. Glass and Konstantinos T. Konstantinidis from Georgia Tech; Samuel Deutsch, Sangeeta Nath, Rex R. Malmstrom and Tanja Woyke from the U.S. Department of Energy; Benjamin K. Stone from Bowdoin College; Laura A. Bristow from the Max Planck Institute; Bo Thamdrup and Morten Larsen from the University of Southern Denmark.
The research was funded by the National Science Foundation (grants 1151698 and 1416673), the NASA Exobiology Program (grant NNX14AJ87G), the Sloan Foundation (RC944), and the U.S. Department of Energy’s Community Science Program. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsoring agencies.
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