Nine graduate students will make up the inaugural Fall 2016 class of the College of Sciences’ interdisciplinary Ph.D. program in Quantitative Biosciences (QBioS). QBioS was established in 2015 by more than 50 participating program faculty in the College of Sciences. It is directed by School of Biological Sciences Professor Joshua S. Weitz.
“QBioS faculty will train Ph.D. students to identify and solve foundational and applied problems in the biological sciences and prepare them for research challenges at scales spanning molecules to ecosystems,” Weitz says.
The QBioS program supports the College’s strategic goal to enhance the research ecosystem and provide new training opportunities. It is Georgia Tech’s third interdisciplinary Ph.D. focusing on life sciences, following the successful models for Bioengineering and Bioinformatics. As in these other programs, QBioS Ph.D. students can select a thesis advisor from the entire program faculty, irrespective of school. In this way, QBioS continues a tradition of fostering innovative, interdisciplinary research and education at Georgia Tech.
Of the nine new students, four are from overseas and one is a Georgia Tech alumnus; five will be based in the School of Biological Sciences, three in the School of Physics, and one in the School of Mathematics.
Shlomi Cohen earned a B.S. in Mechanical Engineering from the Technion-Israel Institute of Technology, in Haifa. Cohen followed his wife to Atlanta after she had been accepted to the Industrial and Systems Engineering Ph.D. program at Tech, and he soon applied for his own doctorate.
Cohen says QBioS is a natural choice for him, despite his engineering background. “I have been interested in biosciences for as long as I can remember,” Cohen says. In fact, he adds, he chose to study mechanical engineering at Technion because they offered a biosciences specialization.
“I look forward to obtaining knowledge and experience that will allow me to gain a set of professional tools to handle real scientific problems and achieve a better understanding of the amazing world around us.” Cohen will be based in the School of Physics during his time in the program.
Nolan Joseph English comes to QBioS with a B.S. in Chemical Engineering from Howard University, in Washington, D.C. English says he was drawn to Tech for its “incredibly strong focus on computer science and interdisciplinary studies that pervade both the culture and research.” That Tech is his father’s alma mater also played a role in his decision.
“The QBioS program allows one to experience many aspects of computational biology – such as systems biology, bioinformatics, and bioengineering – while building a strong core of computational capability and understanding,” English says. “This strong core is what I desire most and is something truly unique to Georgia Tech.”
What most excites English about QBioS is the prospect of learning “how to translate an in silico knowledge base into an in vivo actualization of concept.” For this reason, he says, “I am keenly interested in learning about modeling techniques at the transcriptome and genome levels.” English will be based in the School of Biological Sciences.
Elma Kajtaz earned her bachelor’s degree in behavioral sciences from the University of Sarajevo, in Bosnia-Herzegovina. No longer a stranger to Georgia Tech, Kajtaz had previously worked and studied in the former School of Applied Physiology, now the School of Biological Sciences, with Professor T. Richard Nichols. That research opportunity is what drew Kajtaz initially to Georgia Tech.
“The interdisciplinary and quantitative approach to behavior and physiology emphasized by the QBioS program is perfectly aligned with my research philosophy and interests,” Kajatz says. “I am looking forward to learning and working alongside faculty and researchers from different disciplines to contribute to our understanding of biological systems.” Kajtaz will be based in the School of Biological Sciences.
Alexander Bo-Ping Lee received his bachelor’s degree in mathematical biology at Harvey Mudd College, in Claremont, California. A paper on ant rafts by School of Biological Sciences Associate Professor David Hu intrigued Lee and sparked his interest in attending the QBioS program. Lee is most excited to be a teaching assistant during his time in the program and hopes to become a professor one day, in line with his love of teaching. Lee will be based in the School of Physics.
Joy Elizabeth Putney received her B.S. in Biology and Physics-Engineering from Washington and Lee University, in Lexington, Virginia. She was drawn to QBioS by her love of research that uses quantitative techniques to study biology.
“Life is full of examples of complex systems, from the molecular to the ecological scales, and most complex systems can be best understood using quantitative techniques,” Putney says. She’s excited to start research, taking advantage of the program’s rotation-based structure to gain experience in multiple labs. “This will give me the best opportunity to find a place where I can do research that aligns with my passions,” she says. Putney will be based in the School of Biological Sciences.
Putney may work government or industry after completing the program, but that is a long way in the future. “I hope that Georgia Tech will point me in the right direction,” she says, “even if it ends up being something completely different from what I thought or expected.”
“Georgia Tech is a very prestigious university where science and technology are at the frontiers of knowledge” Márquez-Zacarías says. “I like how students and professors from different fields join efforts to tackle complex problems in the most diverse fields of science.”
Márquez-Zacarías is excited to be part of the diverse and collaborative groups of scientist in the QBioS program. “I can’t imagine a better program for my doctoral degree,” he says. He looks forward to collaborating with various research groups and learning cutting-edge techniques to study how nature works. Márquez-Zacarías will be based in the School of Biological Sciences.
Stephen Anthony Thomas is no stranger to Georgia Tech, where he earned bachelor’s and master’s degrees in electrical engineering. But it is mathematics where Thomas finds his passion.
The QBioS program offers “a great chance to apply a subject I love – mathematics – to areas that can make a real difference to society,” he says.
A potential research focus for Thomas is mathematical modeling for epidemiology. “It’s exciting to be able to work not only at Georgia Tech,” he says, “but also through partnerships with Emory University on critical problems, such as countering antibiotic resistance in bacterial infections.” Thomas will be based in the School of Mathematics.
Hector Augusto Velasco-Perez received his bachelor’s degree in physics from the Faculty of Sciences in the National Autonomous University of Mexico, also in Mexico City. “I was looking for a graduate program and a place that could combine theory and practice, physics and biology, pen and paper, and high-performance computing with GPUs [graphics-processing units],” he says. “I wanted my work to be something that someone can use, something that I can point at – big or small – and say, ‘Look, I did that!’.”
QBioS fits the bill, and Velasco-Perez looks forward to working in a diverse community. The QBioS program “is a perfect opportunity for new ideas to be created,” he says. Velasco-Perez will be based in the School of Physics.
Seyed Alireza Zamani-Dahaj received his master’s degree in physics from McMaster University, in Hamilton, Ontario, Canada. He was drawn to QBioS by the wide range of classes and the multiple labs doing interesting research. “Being among the first class of the QBioS Program is very exciting,” Zamani-Dehaj says. He will be based in the School of Biological Sciences.
“We warmly welcome our new graduate students in QBioS,” says College of Sciences Dean Paul M. Goldbart. “We look forward to their unique contributions to the College’s tradition of forging new paths of discovery.”
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Benjamin Franklin famously wrote, “In this world, nothing can be said to be certain, except death and taxes.”
In addition to being a founding father of the United States, Franklin also was a scientist, so he’d probably be interested in the Bioinformatics Graduate Program at the Georgia Institute of Technology, where another kind of certainty has been in play.
For the last five years every graduate of the program found the work they wanted – a 100-percent job placement rate. Well, almost. It turns out, there’s a tiny wrinkle in that impeccable run of success, according to program director King Jordan.
“It’s a lofty claim, to be sure, that we’ve been at 100 percent for years,” says Jordan, researcher at the Petit Institute for Bioengineering and Bioscience and associate professor in the School of Biological Sciences. “But there is one person we know for sure that isn’t working right now. He isn’t sure what he wants to do yet. That’s why he isn’t employed.”
For now, 99-plus percent will do. It’s a high success rate, 10 years in the making, since Jordan arrived at Georgia Tech to help develop the bioinformatics curriculum and grow the program.
“The program didn’t have the best record at the time; some of our graduating students were struggling to find employment,” says Jordan, who came to Georgia Tech from the National Center for Biotechnology Information at NIH.
Jordan and his colleagues revamped the curriculum, emphasizing active learning and practical skills. “We made the program more project oriented,” he says.
One of the first courses, and part of the core curriculum, is programming for bioinformatics. It’s taught largely by Ph.D. students and is a fundamental first-step, designed to bring everyone up to the same speed on the primary tool of the trade – the computer.
“Bioinformatics lies at the intersection of biology and computer science,” Jordan says. “So we have a diverse cross-section of students. At one end are straight biologists, like me. At the other end, we have the programmers.”
Students are given coding assignments every week, and every assignment is grounded in the actual analysis of data.
The computational genomics course takes data analysis up to another level. Students are charged with analyzing sets of genomic sequences from microbial pathogens for the Centers for Disease Control and Prevention (CDC).
The relationship between the CDC and the Bioinformatics Graduate Program has had far-reaching impact. Jordan and a team of graduate students worked closely with CDC to develop computational tools for microbial genome analysis that helped trace the source of listeria outbreaks in Colorado and an E. coli outbreak in Europe.
“Students are producing products and technology that is being used by the CDC to address real world public health challenges,” says Jordan, whose team developed and teaches the course in collaboration with the CDC.
The tools needed for a course like computational genomics keep changing, so students are expected to stay abreast of an ever-shifting technological landscape, which is moving the science briskly forward. Think about it. The Human Genome Project, completed in 2003, took 10 years and $3 billion to sequence one genome – something that can be done in a day for about a thousand dollars now.
“If I teach you how to use program X today, by next year it will probably be obsolete,” Jordan says.
Consequently, students are presented with the project goals and the different technical options, and then asked to evaluate which computer programs (which tools, which options) to use in their analysis.
“Mostly, they wind up using a combination of programs,” Jordan says. “It’s cliché, but it’s like teaching them how to fish, how to acquire and evaluate the technology to complete the project.”
While the Georgia Tech curriculum and deep-dive project experience has been an obvious selling point for the job seekers, the market for their services has expanded as well.
“There’s more demand in the market than we can meet,” says Jordan.
The Georgia Tech Bioinformatics Program is trying to help meet the demand by adding more students – this fall’s incoming class of 52 students (40 master’s, 12 PhD) is the biggest in the program’s history, and as usual, they come from a range of backgrounds.
So, what are all of these students doing after they graduate?
For one thing, they’re working in university and research institute labs. Biology is becoming a ‘big data’ science as biologists are generating massive data sets in the era of high-throughput experimentation techniques. Consequently, biologists today need people who are competent in the skills and tools used to analyze those huge data sets.
“The technological revolution in DNA sequencing, which has vastly outpaced increases in computing speed over the last decade, is fundamentally transforming biological sciences in nearly all disciplines,” explains Jung Choi, associate professor in the School of Biological Sciences, and director of the Professional Science Masters (M.S.) track in the bioinformatics program. Jordan directs the Ph.D. track.
“The explosion of big data in biological sciences created a shortfall in people trained to manage and make sense of the data in the context of biology,” Choi adds. “Bioinformatics, genomics, and computational biology are among the most rapidly advancing fields. In a research setting, our students learn how to evaluate and adapt the best new tools and methods that emerge every year.”
Bioinformatics grads are finding their way into government labs – once again, the CDC has come up big, hiring seven bioinformatics grads from the past two classes. And they’re also going into the private sector.
“Within biotech are two big sectors that are frequent employers of our graduates,” says Jordan. “The pharmaceutical industry and the agriculture industry.”
Then there is another route some students are choosing as a result of the research-intensive nature of the bioinformatics program. About a quarter of the Master’s students choose to continue their education and enter Ph.D. programs.
“M.S. students can go right away to pharmaceutical companies and make big bucks, but some who are exposed to research are becoming passionate about that, so they decide to go on and pursue the Ph.D.,” Jordan says. “That’s what I call an unanticipated benefit of our revamped focus.”
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The College of Sciences has selected the 2016 recipients of the Cullen-Peck Fellowships in the College of Sciences: Tamara Bogdanovic, an assistant professor in the School of Physics; Andrew V. Newman, an associate professor in the School of Earth and Atmospheric Sciences, Frank J. Stewart, an assistant professor in the School of Biological Sciences, and Lewis A. Wheaton, an associate professor in the School of Biological Sciences.
“The fellowships recognize exciting research accomplishments by College of Sciences faculty at the associate professor or advanced assistant professor level,” says College of Sciences Dean Paul M. Goldbart. “The goal is to help recipients take their research programs in new directions.”
The fellowships are made possible by a generous gift to the College of Sciences from alumni Frank H. Cullen (B.S. in Mathematics with Honors 1973, M.S. in Operations Research 1975, Ph.D. Engineering 1984) and Libby Peck (B.S. in Applied Mathematics 1975, M.S. in Industrial Engineering 1976).
“We in the College of Sciences are grateful for the generosity of alumni who encourage our faculty to take intellectual risks in their research,” Goldbart says. “The Cullen-Peck fellowships help ensure that our research is pushing the frontiers of knowledge. Congratulations to the 2016 Cullen-Peck fellows, and thank you for all you do for the Georgia Tech community.”
Tamara Bogdanovic is a theoretical astrophysicist whose research interests include the ins and outs of some of the most massive black holes in the universe. Her group investigates observational signatures associated with supermassive black holes interacting with gas and stars in galactic nuclei.
Recently her group offered a plausible solution to a puzzle: Why is the center of the Milky Way galaxy full of young stars but has very few old ones? Scientists suspect that remnants of old stars are present but are too faint to be detected by telescopes. The theory is that old stars have been dimmed by repeated collisions with the accretion disk – a disk-like structure of diffuse material – that at some point in the past orbited a supermassive black hole in the center of our galaxy.
Computer simulations using models of red giant stars suggest that such collisions could have inflicted significant damage to old stars, making them invisible, only if the accretion disk was sufficiently dense and massive. The study, published in The Astrophysical Journal, is the first to run computer simulations on the theory, which was introduced in 2014.
“The generous support of the Cullen-Peck fellowship will allow us to foray into unexplored aspects of the interaction of matter and radiation in the deep gravitational wells of black holes,” Bogdanovic says. She hopes to be able to make more accurate theoretical predictions about the signatures of accreting supermassive black holes in distant galaxies, which can be confirmed by observations.
Trained as a geophysicist, Andrew V. Newman studies the active deformation and failure of Earth's rigid outer layer in areas of frequent seismic and volcanic activity. And he wants to understand their impact on society.
Of particular interest are megathrust faults, which are responsible for the largest, and some of the deadliest, earthquakes. For example, using a small network of seismometers and Global Positioning System (GPS) sensors, Newman’s team mapped a segment of a megathrust fault in Costa Rica that was locked, loaded, and ready for failure. They reported the discovery in the Journal of Geophysical Research in June 2012. Three months later, the earthquake occurred.
Newman’s group again measured the GPS sites and reported in Nature Geoscience that the anticipated earthquake occurred directly in the locked region and with approximately the magnitude the team estimated was possible. Such pre-event imaging and discovery of dangerous megathrust loading is rare because most such earthquakes occur underwater, where GPS doesn’t work. Likewise, these zones are more concerning, because they generate dangerous tsunami waves.
With the support from the Cullen-Peck fellowship, Newman plans to “explore new and low-cost methodologies for making observations of precise ground deformation on the seafloor.” In the journal Nature, Newman had argued that such tools are needed to explore 90% of the active plate boundaries to both better understand dynamics of tectonic plate interaction and to illuminate the risk associated with their geologic hazards, including tsunami generation and underwater volcanism.
Frank J. Stewart explores the genetic diversity of marine microorganisms in hopes of answering two fundamental questions: How do ecological and evolutionary processes create and structure genetic diversity? How is this genetic diversity linked to the diverse biogeochemical functions of microorganisms in nature? In particular, his group is interested in how oxygen loss affects the diversity and metabolism of marine microbes.
In early August 2016, Stewart and others reported in the journal Nature the discovery of new bacterial strains that thrive in oxygen-poor parts of the ocean. The new strains breath nitrogen-containing nutrients in place of oxygen. Their metabolism thus helps deplete nitrogen from the oceans, making the oxygen-poor zones even more uninhabitable, as well as kick-starting metabolic processes that generate nitrous oxide, a potent greenhouse gas.
The zinger is that climate change is causing oxygen-poor zones to expand, meaning these new strains will play an increasingly larger role in shaping ocean chemistry.
Stewart will use the award to advance a project to analyze whole-genome gene expression data (transcriptomes) from single bacterial cells. Single-cell transcriptomics has been used to study eukaryotic cells, he says, but has been difficult when applied to bacterial cells. With collaborators David A. Weitz and Peter R. Girguis, at Harvard University, Stewart is optimizing methods to recover bacterial transcriptomes from single cells.
If the method works, Stewart says, “it could enhance understanding of microbial ecology and diversity in all of the environments our lab studies, including those in the open ocean and those in the guts of animals.”
Research in the laboratory of Lewis A. Wheaton aims to understand how healthy people plan and execute complex tasks, such as kicking a ball or using tools. At present, he is focused on understanding motor skill development across many populations and the neurophysiological relationships between motor development and lexical (vocabulary) development in pediatric populations. The goal is to reveal couplings of language and motor imitation.
Another focus area is motor skill development after traumatic amputation. Wheaton would like to understand how central neural networks for motor learning are affected after amputation and what role they play in the use of prostheses.
The award will help set up new human neuroimaging studies to identify functional and neuroanatomical changes related to motor learning, Wheaton says. “It will also partially fund a student who is expanding this work to develop better therapeutic approaches for patients with neurological injury and disease.”
How did life on Earth originate from simple molecules? This question is one of the deepest, most fundamental questions of science, and it remains unanswered.
In Georgia Tech’s College of Sciences, scientists are trying to decipher the origin of life. Among them is Loren D. Williams, a professor in the School of Chemistry and Biochemistry and a member of the Parker H. Petit Institute of Bioengineering and Biosciences.
For Williams, part of the answer has to come from the ribosome. This gigantic molecular machine comprising ribonucleic acids (RNA) and proteins enables a key distinction of life: translation of genetic information to proteins.
How did translation begin? Work in Williams' lab suggests that translation is the product of molecular symbiosis, that ancestors of RNA and protein were molecular symbionts, and that life arose from the coevolution of proteins and RNA. That startling notion challenges the popular “RNA world” hypothesis of the origin of life. That world posits a time when life was based only on RNA, RNA-catalyzed transformations, and RNA-based genetic material; proteins, the ribosome, and translation appeared later.
At the meeting of the American Chemical Society in Philadelphia, Williams makes the case that the early history of the ribosome is also the history of the origin of life.
Williams and his coworkers base their conclusions on meticulous analysis of the “fossil record” in all ribosomes. As trees imprint events in their rings, or ice cores suspend time by preserving matter in frozen columns, ribosomes are time machines, Williams says, one “that allows us to look at the behaviors of ancient molecules 3.8 billion years ago.”
Crystal structures indicate that the modern ribosome grew by accretion, Williams says. By peeling away the layers deposited in the ribosome over almost 4 billion years, Williams and coworkers reached inside the so-called common core, which is the common denominator and oldest part of biology. Deep inside is the peptidyl transferase center, which links amino acids through peptide bonds “This part of the ribosome originates in chemistry,” Williams says. “It is pre-biology.”
If two amino acids are located within the peptidyl transferase center, they will easily form a peptide bond. “But as soon as you do that in the absence of the ribosome, the ends of the amino acids come together, forming a cyclic structure,” Williams says. Polymers cannot form. But if the ends are kept apart, by the primitive ribosome, a chain of peptide bonds could grow into a polymer.
As it happens, a feature of the ancient ribosome is a hole in the middle, foreshadowing the tunnel through which proteins leave modern ribosomes after they are made. “We think that an original function of the ribosome was not to catalyze peptide bond formation but to keep amino acids from forming cyclic structures and thereby form longer peptides,” Williams says.
The tunnel through which all proteins pass is a constant in the evolution of the ribosome. By examining crystal structures and mapping how modern ribosomes grew from the common core, Williams gleaned that ribosomes evolved to make this tunnel long and rigid.
Why? Williams suggests that without a long tunnel, a synthesized protein would fold at once, become active, and start eating the ribosome’s structure. “The tunnel is saying to the protein, no you cannot become functional yet.”
Ribosome crystal structures suggest something else: When early ribosomes made small peptides that were not capable of folding, some of these peptides stuck to and accreted on the ribosome. “We think the ribosome started making peptides in the first place to give itself greater stability,” Williams says. In making peptides that became bound to the ribosome like scaffolding, the ribosome became bigger and more stable.
As evidence, Williams presents the protein fossils in ribosomes. The oldest ones are frozen random coils “That’s the first thing we think the ribosome made. They got stuck, they didn’t fold. They don’t look like modern proteins.”
Next are isolated beta hairpins. “Nowhere else in biology will you see isolated beta hairpins without other protein around it,” Williams notes. “Only in the core of the ribosome do you see beta hairpins surrounded by RNA.” These isolated beta hairpins are the most ancient folded proteins in biology, he says.
Then come more modern proteins, made of beta sheets and alpha helices, with hydrophobic exteriors and hydrophilic interiors and the ability to fold to globular forms.
“Our results show that protein folding from random-coil peptides to functional polymeric domains was an emergent property of the interactions of ribosomal RNA and peptides,” Williams says. “The ribosome is the cradle of protein evolution.”
Along with Nicholas V. Hud, a professor at the School of Chemistry and Biochemistry and the director of the Center for Chemical Evolution, Williams and other origin-of-life researchers in Georgia Tech propose that chemical evolution—driven by assembly and other processes that increase stability—gradually converted to biological evolution, involving genes, enzymes, and ribosomes.
“We believe that chemical evolution was driven by assembly,” Williams says. “In biology, things that are assembled live longer chemically than those that are not. A folded protein is chemically stable. Unfold it, and it falls apart.” So it was in chemical evolution. Things that could assemble existed longer than those that couldn’t.
“If you had a molecule that could assemble and make peptides that bound to it, and they co-assemble, all of a sudden you have something better,” Williams says. “We think the reason proteins came into biology was that they stabilized the ribosome and protected it from degradation. The ribosome was looking out for itself. It was an evolutionary process by the ribosome, for the ribosome, and of the ribosome.
“We have the historical record or molecules. These things are preserved in the ribosome, we can see them. There is a molecular record of the origin of life.”
The evolution of the ribosome, illustrating growth of the large (LSU) and small (SSU) subunits, first as separate units and eventually as parts of a whole.
In Phase 1, ancestral RNAs form stem loops and minihelices. In Phase 2, LSU, which has a short tunnel, condenses short, nonspecific, peptide-like oligomers. Some of these oligomers bind back onto the ribosome and stabilize it. At this point, SSU may have a single-stranded RNA-binding function. In Phase 3, the subunits associate, mediated by the expansion of tRNA from a minihelix to its modern L-shape. The tunnel elongates. In Phase 4, the two subunits associate and they evolve together. The ribosome is a noncoding diffusive ribozyme in which proto-mRNA and the SSU act as positioning cofactors, producing peptide-like oligomers, some of which form beta-hairpins. In Phase 5, the ribosome expands to an energy-driven, translocating, decoding machine. Phase 6 marks completion of the common core with a proteinized surface (the proteins are omitted for clarity). mRNA is shown in light green. The A-site tRNA is magenta, the P-site tRNA is cyan, and the E-site tRNA is dark green.
Georgia Tech now offers an interdisciplinary Ph.D. program in Ocean Science and Engineering (OSE). The new program aims to train ocean scientists and engineers by combining basic and applied sciences with innovative ocean technologies. Students in the program will participate in interdisciplinary research at the frontiers of the physical, biological, chemical, and human dimensions of ocean systems.
A partnership of the College of Sciences and the College of Engineering, the program involves faculty from the Schools of Earth and Atmospheric Sciences (EAS), Biological Sciences, and Civil and Environmental Engineering (CEE). The program’s director and co-director are Emanuele Di Lorenzo and Annalisa Bracco, both professors in EAS.
“The greatest challenges in research result from the growing complexity, interconnectedness, and linkages of phenomena, which cannot be addressed within traditional disciplinary boundaries. This applies especially to the ocean—the largest environmental resource on Earth,” Bracco said. “Chemical, biological, and physical processes in ocean cannot be viewed in isolation.”
What’s needed, she said, is an integrated approach to interpreting scientific data and developing effective solutions to immediate problems, such as loss of coral reefs, and their long-term consequences, such as loss of biodiversity.
“Georgia Tech is one of a very few institutions with the engineering and scientific prowess and the interdisciplinary culture to effectively address these critical challenges,” Di Lorenzo said.
Kevin A. Haas, in CEE, said the program brings together for the first time the large number of researchers focused on ocean studies but scattered across Georgia Tech academic units. “We will be able to take a more holistic approach,” he said, “through collaborations between scientists and engineers to address issues such as ecological impacts of global climate change and develop engineering solutions to adapt to or mitigate these impacts.”
OSE seeks students with interest and curiosity in the program’s themes: ocean technology, ocean sustainability, ocean and climate, marine living resources, and coastal ocean systems.
“Our goal is to develop a pipeline of in-demand ocean experts for industry, government, and academia,” Di Lorenzo said.
Graduate programs in ocean sciences and engineering are not new. Georgia Tech’s OSE is unique in combining basic and applied research in one degree offering. “We aim to find solutions to ocean-related problems by integrating science and engineering. This is a fundamental challenge that is not addressed by competing programs,” Di Lorenzo said.
The inaugural class of OSE students will enroll in Fall 2017. Applications are due Dec. 8, 2016.
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Will Ratcliff is having a moment in the spotlight for getting yeast and algae to jump through hoops to new evolutionary heights.
The magazine Popular Science has heaved the researcher from the Georgia Institute of Technology into its annual list “The Brilliant 10,” a select roster of “the 10 most innovative young minds in science and technology.” Ratcliff was praised for advancing the study of cellular evolution.
PopSci cited his work demonstrating how single-cell organisms may have transitioned into simple multicellular organisms ages ago. It’s widely seen as an arduous evolutionary leap, since single cells had to forfeit a lot of their own fitness for the greater good of creating viable cell groups.
“William Ratcliff revealed surprising insights into what might have been necessary for this transition to occur,” Popular Science wrote in its September/October edition. He has illuminated “one of the greatest mysteries of life.”
The needs of the many
Ratcliff, an assistant professor in Georgia Tech's School of Biological Sciences, has put thousands of generations of yeast and many generations of algae cells through stresses in the lab devised to get them to evolve better survival strategies around forming cohesive groups.
“We’re figuring out kind of clever ways to get them to form groups and then for those groups to become more complex,” he said.
The idea is to end up with a rudimentary multicellular being with cells taking on specialized roles, a very early step on the pathway to organ development. But the first advantage to group formation is simple -- size. Bigger is often better.
“A lot of small predators have small mouths that are great at eating single-cells,” Ratcliff said. But big multicellular cell clusters are too big for these predators to get their mouths around. Clustered cells survive to pass on their genes.
Race to the bottom
To accelerate the evolution of yeast from individuals cells into cell groups called “snowflakes,” one of his signature achievements, Ratcliff has selected for yeast cells that sink more quickly. There, again, big clusters sink better than single cells.
Once clusters are done outcompeting the unicells, they compete against each other. “It’s remarkable how quickly snowflake yeast clusters evolve new traits that let them win this race,” he said.
While the group gains various strengths, it sacrifices the viability of individual cells. “They evolve a division of labor in the group, in which some of them commit suicide,” Ratcliff said. That changes reproductive patterns, which makes the clusters’ progeny more competitive.
The loss of individual cell fitness is extensive.
The more robust a cluster gets, the less likely its individuals are to survive if they are caused to revert back to individual cells. It’s like an odd twist on the traditional marriage vows: Part, and you will die.
Much of Ratcliff’s research is funded by NASA’s Exobiology program and the National Science Foundation.
Felt it coming
Before Popular Science called for an interview for its four-paragraph nod, Ratcliff had sensed something was coming. For a few months, while the magazine cemented its list, it asked around at scientific societies about noteworthy up-and-coming researchers.
As a result, Ratcliff received some veiled tips.
“A couple of colleagues of mine said, ‘Hey man, I got a call from a reporter. I can’t tell you anything about it, but you may be hearing something soon,’” he said.
When PopSci called, a reporter told Ratcliff that many scientists had mentioned him, strongly influencing the decision to name him one of "The Brilliant 10." “That was very touching that people within the research community said to them they should look at my lab,” Ratcliff said.
Hail Mary pass
Life’s small coincidences have helped guide Ratcliff’s academic strivings down the path of evolutionary research.
His career in biology spawned from childhood, when his parents carted him and his brother Felix off in their summers to woodland family cabins next to craggy Pacific Coast cliffs near Mendocino, California. “There was really nothing to do except to run around the forest and the ocean checking out the lives of plants and animals,” Ratcliff said.
They got hooked; both brothers became biologists.
Plants became Ratcliff’s passion at an early age, which led to a bachelor of science in plant biology from the University of California, Davis, but that threw his career a serendipitous curve. “I thought it would have a lot to do with ecology, but it turned out to be mostly cellular biology.”
The decision to see if yeast cells could be coaxed into making the leap to multicellularity was also slightly capricious. “There was a lot of doubt surrounding it, but I thought, ‘Why not just give it a try and see,’" said Ratcliff, whose Ph.D. is in ecology.
He was astonished when that longshot worked. “It was a kind of Hail Mary pass,” he said. It led to a dedicated research specialization and a notable body of continuing work.
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Using cryo-electron tomography, Georgia Tech and Emory University researchers have captured images of measles viruses as they emerge from infected cells. The work advances the understanding of measles and related viruses and could suggest antiviral drug strategies likely to work across multiple members of the family that includes measles virus.
The results were published in Nature Communications.
Scientists led by Elizabeth Wright and Zunlong Ke say they can discern an internal matrix protein acting as a scaffold, with the encapsidated genetic material visible as “snakes” close to the viral membrane.
An effective vaccine is available against measles virus, which is a highly infectious pathogen. Yet scientists still don’t understand a lot about it, Ke says. Understanding the internal organization of measles virus could guide the study of related viruses, such as parainfluenza and respiratory syncytial virus (RSV), which are common causes of respiratory illnesses, as well as Nipah virus, an inspiration for the film “Contagion.”
Wright is an associate professor of pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta, director of the Robert P. Apkarian Integrated Electron Microscopy Core, and a Georgia Research Alliance Distinguished Investigator. She has an adjunct appointment in the Georgia Tech School of Biological Sciences.
Ke is a former Georgia Tech Ph.D. student of Wright’s. Ke is starting a postdoctoral position this summer at the MRC Laboratory of Molecular Biology in Cambridge, U.K.
After working with purified viruses for a long time, Wright, Ke, and colleagues decided to examine virus-infected cells. The team collaborated with Richard Plemper, who specializes in measles virus and is now at Georgia State University.
The family of viruses that includes measles, called paramyxoviruses, is difficult to handle because of their low titers, instability, and heterogeneity, Wright says. For structural studies, researchers usually concentrate and purify viruses by centrifuging them through thick solutions. But this method is tricky for measles virus, which are squishy and prone to bursting. For this reason, they are difficult to visualize.
“Instead, we grow and infect the cells directly on the grids we use for microscopy and rapidly freeze them, right at the stage when they are forming new viruses,” Ke says.
Improvements in technology have increased the resolution of imaging. Cryo-electron tomography, which is ideal for viruses that come in different shapes and sizes, uses an electron microscope to obtain a series of 2D pictures of the viruses as the sample holder is tilted to multiple angles along one axis. The images and the angular information are then used to compute the 3D volume of the virus, much like a medical CT scan, Wright says.
“We would never see this level of detail with purified virus, because the process of purification disrupts and damages the delicate virus particles,” she says. “With the whole-cell tomography approach, we can collect data on hundreds of viruses during stages of assembly and when released. This allows us to capture the full spectrum of structures along the virus assembly pathway.”
For example, the scientists can now see the organization of glycoproteins on the surface of the viral membrane. Previous work showed two glycoproteins were present on the membrane, but they were a “forest of trees,” with insufficient detail to identify each one.
In this study, the team resolved the two glycoproteins and determined that one of them, the fusion (F) protein, is organized into a well-defined lattice supported by interactions with the matrix protein. In addition, they could see “paracrystalline arrays” of the matrix protein, called M, under the membrane. The arrays had not been seen in measles virus-infected cells or individual measles virus particles before, Wright says. Under the microscope, these arrays look like Lego grid plates, from which the rest of the virus is built and ordered.
The new 3D structures also argue against a previous model of viral assembly, with ribonucleoprotein genetic material as a core and the M protein forming a coat around it.
The scientists are still figuring out what makes measles virus take a bulbous shape while RSV is more filamentous. Ke thinks the scaffold role of M is similar for related viruses; however, as the virus assembles, individual structural proteins may coordinate uniquely to produce virus particles with different shapes that better support their replication cycle.
This work was supported in part by Emory University; Children’s Healthcare of Atlanta; the Georgia Research Alliance; the Center for AIDS Research at Emory University (P30 AI050409); the James B. Pendleton Charitable Trust; public health service grants R01AI083402 and R01HD079327, R01GM114561, R21AI101775, and F32GM112517; and NSF grant 0923395.
EDITOR’S NOTE: This article is an abridged and slightly modified version of the original story by Quinn Eastman published in the Emory News Center on April 30, 2018.
For much of its first two billion years, Earth was a very different place: oxygen was scarce, microbial life ruled, and the sun was significantly dimmer than it is today. Yet the rock record shows that vast seas covered much of the early Earth under the faint young sun.
Scientists have long debated what kept those seas from freezing. A popular theory is that potent gases such as methane – with many times more warming power than carbon dioxide – created a thicker greenhouse atmosphere than required to keep water liquid today.
In the absence of oxygen, iron built up in ancient oceans. Under the right chemical and biological processes, this iron rusted out of seawater and cycled many times through a complex loop, or “ferrous wheel.” Some microbes could “breathe” this rust in order to outcompete others, such as those that made methane. When rust was plentiful, an “iron curtain” may have suppressed methane emissions.
“The ancestors of modern methane-making and rust-breathing microbes may have long battled for dominance in habitats largely governed by iron chemistry,” said Marcus Bray, a biology Ph.D. candidate in the laboratory of Jennifer Glass, assistant professor in the Georgia Institute of Technology’s School of Earth and Atmospheric Sciences and principal investigator of the study funded by NASA’s Exobiology and Evolutionary Biology Program. The research was reported in the journal Geobiology on April 17, 2017.
Using mud pulled from the bottom of a tropical lake, researchers at Georgia Tech gained a new grasp of how ancient microbes made methane despite this “iron curtain.”
Collaborator Sean Crowe, an assistant professor at the University of British Columbia, collected mud from the depths of Indonesia’s Lake Matano, an anoxic iron-rich ecosystem that uniquely mimics early oceans. Bray placed the mud into tiny incubators simulating early Earth conditions, and tracked microbial diversity and methane emissions over a period of 500 days. Minimal methane was formed when rust was added; without rust, microbes kept making methane through multiple dilutions.
Extrapolating these findings to the past, the team concluded that methane production could have persisted in rust-free patches of ancient seas. Unlike the situation in today’s well-aerated oceans, where most natural gas produced on the seafloor is consumed before it can reach the surface, most of this ancient methane would have escaped to the atmosphere to trap heat from the early sun.
In addition to those already mentioned, the research team included Georgia Tech professors Frank Stewart and Tom DiChristina, Georgia Tech postdoctoral scholars Jieying Wu and Cecilia Kretz, Georgia Tech Ph.D. candidate Keaton Belli, Georgia Tech M.S. student Ben Reed, University of British Columbia postdoctoral scholar Rachel Simister, Indonesian Institute of Sciences researcher Cynthia Henny, Skidaway Institute of Oceanography professor Jay Brandes, and University of Kansas professor David Fowle.
This research was funded by NASA Exobiology grant NNX14AJ87G. Support was also provided by a Center for Dark Energy Biosphere Investigations (NSF-CDEBI OCE-0939564) small research grant, and by the NASA Astrobiology Institute (NNA15BB03A). 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 organizations.
CITATION: Bray M.S., J. Wu, B.C. Reed, C.B. Kretz, K.M. Belli, R.L. Simister, C. Henny, F.J. Stewart, T.J. DiChristina, J.A. Brandes, D.A. Fowle, S.A. Crowe, J.B. Glass. 2017. "Shifting microbial communities sustain multi-year iron reduction and methanogenesis in ferruginous sediment incubations," (Geobiology 2017). http://dx.doi.org/10.1111/gbi.12239.
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The College of Sciences held its annual summer dinner on Aug. 23, 2016. The festive occasion welcomed new faculty members and recognized excellence in research, teaching, and service.
College of Sciences Dean Paul M. Goldbart welcomed colleagues joining the College in the 2016-17 academic year: Tamara Pearson and Lorna Rivera, in CEISMC; Will Gutekunst and Henry La Pierre, in the School of Chemistry and Biochemistry; Liang Han, Colin Harrison, and Frank Rosenzweig, in the School of Biological Sciences; Jennifer Hom, Christopher Jankowski, Lutz Warnke, and Mayya Zhilova, in the School of Mathematics; and Elisabetta Matsumoto and Colin Parker, in the School of Physics.
Goldbart also recognized J. Todd Streelman, the new chair of the School of Biological Sciences, which emerged on July 1, 2016, from the reorganization of the former School of Applied Physiology and School of Biology. Goldbart acknowledged T. Richard Nichols and Terry Snell, chairs of the former schools, for their efforts in launching the new school.
Celebrating excellence in research, teaching, and service was the evening’s center piece, beginning with the 2016 Faculty Mentor Awards to Luca Dieci, of the School of Mathematics; Facundo M. Fernandez, of the School of Chemistry and Biochemistry; and Rodney J. Weber, in the School of Earth and Atmospheric Sciences.
Carrie G. Shepler, of the School of Chemistry and Biochemistry, received the 2016 Eric R. Immel Memorial Award for Excellence in Teaching. The award is made possible by School of Mathematics alumnus Charles J. Crawford.
The 2016 Cullen-Peck Faculty Fellowship Awards in the College of Sciences went to Tamara Bogdanovic, of the School of Physics; Andrew V. Newman, of the School of Earth and Atmospheric Sciences; and Frank J. Stewart and Lewis A. Wheaton, of the School of Biological Sciences. These awards are made possible by the generosity of School of Mathematics alumni couple Frank H. Cullen and Libby Peck.
Daniel Margalit was celebrated as the inaugural 2016 Leddy Family Faculty Fellow. The award is made possible by the generosity of School of Physics alumnus Jeffrey Leddy and his wife, Pamela.
“It is invigorating to start the school year by warmly welcoming new colleagues into our scholarly community and celebrating our outstanding teachers, researchers, and mentors,” Goldbart said. “We are proud to have so many exceptional faculty members, and I am especially grateful for the generosity of our thoughtful alumni, which makes it possible for the College to enable our colleagues to achieve the highest level of success in their teaching, research, and service.”
More photos from the 2016 summer dinner can be viewed at http://bit.ly/2bz1Is8.
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Remnants of extinct monkeys are hiding inside you, along with those of lizards, jellyfish and other animals. Your DNA is built upon gene fragments from primal ancestors.
Now researchers at the Georgia Institute of Technology have made it more likely that ancestral genes, along with ancestral proteins, can be confidently identified and reconstructed. They have benchmarked a vital tool that would seem nearly impossible to benchmark. The newly won confidence in the tool could also help scientists compute ancient gene sequences and use them to synthesize better proteins to battle diseases.
For some 20 years, scientists have used algorithms to compute their way hundreds of millions of years back into the evolutionary past. Starting with present-day gene sequences, they perform what’s called ancestral sequence reconstruction (ASR) to determine past mutations and figure out the genes’ primal forerunners.
“With the help of ASR, we can now actually build those ancient genes in the laboratory and express their encoded ancient proteins,” said Eric Gaucher, an associate professor at Georgia Tech’s School of Biological Sciences. In a separate project, his lab is computing ancient proteins that were very effective in blood clotting 80 million years ago, in hopes of using them to fight hemophilia today.
That protein comes from a common ancestor humans share with rats.
Time travel substitute
But ASR algorithms have faced logical criticism. Species based on those primal genes are long extinct, and scientists can’t travel back in time to observe mutations that have happened since. So, how can anyone find any physical benchmark to verify and gauge ASR?
A team of researchers led by Gaucher did it by building an evolutionary framework out of myriad mutations. Then they benchmarked ASR algorithms against it – no time machine required. Their results have shored up confidence that the widely used algorithms are working as they should.
“Most of them did a very good job – 98% accurate,” Gaucher said of contemporary algorithms’ ability to compute ancient gene sequences. Their determination of proteins encoded by those sequences was virtually perfect.
Gaucher, research coordinator Ryan Randall and undergraduate student Caelan Radford published their results on Thursday, September 15, 2016, in the journal Nature Communications. Their research has been funded by the NASA Exobiology program, E.I. du Pont de Nemours and Company (DuPont) and the National Science Foundation.
Holographic tree branches
Ancestral sequence reconstruction is like making a family tree for genes.
The many twigs and branches at the treetop would be sequences from species alive today. Shimmying down the tree, called a phylogeny in genetics, you would find their common ancestors, millions of years old, in the lower branches.
There’s a caveat; none of the lower branches exist any longer. They vanished in the extinction of the species bearing those genetic sequences.
ASR computes them back into place using algorithms based on scientific models of evolution. It’s like replacing missing branches with holographic duplicates.
Algorithm horse race
The accuracy of those evolutionary models has been a historic sticking point. And doubts about the algorithms based on them linger in some circles that hold on to an old, tried-and-true algorithm.
So, Gaucher and researcher coordinator Randall pitted the contemporary model-based, or “maximum likelihood,” algorithms in a race against the generic, or “parsimony,” algorithm.
“Parsimony follows the simplest notion of evolution, which is that very little mutation occurs,” Randall said. The models behind contemporary “maximum likelihood” algorithms, by contrast, are laced with filigree, data-packed details.
For the race, Randall made a track of sorts by putting a gene sequence that made a single protein through multiple mutations to construct a real-life phylogeny. She used methods that closely mimicked natural evolution, but that were much, much faster.
Rainbow phylogeny racetrack
In cells, enzymes called polymerases aid in DNA duplication. They work very efficiently, but their rare mistakes are the most common source of mutations, and Randall took her lead from this.
“We used a polymerase that is error-prone to speed up mutations, and speed up evolution,” she said.
The genes used at the starting point of the lab evolution made a protein that fluoresced red when placed in bacteria. As significant mutations arose, the proteins began changing color. Bacteria containing green fluorescing proteins popped up among the red ones.
Randall divided bacteria with major mutations into new groups, creating branches in the phylogeny, as she went. Many mutations produced new colors – yellow, orange, blue, pink – and Randall ended up with a gene family tree in rainbow colors.
Show me the phenotype
The colors reflected not only new gene sequences but also new phenotypes – the actual proteins they produced, the organism’s working molecules.
“What counts is phenotype,” Gaucher said. “When you analyze DNA strictly by itself, it ignores the context, in which that DNA is connected to phenotype,” he said.
DNA can mutate and still encode the same amino acids, protein’s component parts. Then the mutation has no real effect. But when mutations cause DNA to encode different amino acids, they’re more significant.
A worthy test of ancestral sequence reconstruction algorithms must therefore include phenotype. And Randall took this into account when she selected mutated proteins.
“I selected for variants to purposely make it hard on the algorithms to infer the phenotypes,” she said. The race ensued, and the algorithms got limited information to infer the evolutionary tree’s many dozens of past mutations.
ASR a sure bet
Though the tried-and-true parsimony algorithm performed well, maximum likelihood performed better. “Even though it got the same number of residues (DNA sequences) wrong as parsimony, the incorrectly inferred sequences were still more likely to encode the right phenotypes,” said undergraduate student Caelan Radford, who analyzed the experiment’s statistics.
The margin of error was so tiny that it would not interfere in the determination of past species.
The experiment’s outcome was not too surprising, because prior simulations had predicted it. But the researchers wanted the scientific community to have physical proof that feels trustier than proof from a computer. “It’s a computer algorithm. It will do what you will tell it to do,” Gaucher said.
Short history of ASR
Doubts about ancestral sequence reconstruction -- and maximum likelihood algorithms in particular -- go far back. The idea of performing ASR first came up in 1963, but it didn’t get started until the 1990s, and back then, researchers battled fervently over wide-ranging methods.
“People would come up with the craziest notion as to why one model was best,” Gaucher said. “They’d say, ‘Well, if I simulate this weird mode of evolution along these branches here, my algorithm will work better than your algorithm.’”
The parsimony algorithm was a way of reigning in the chaos that grew out of a lack of data in evolutionary models at the time. “When the model is wrong, ‘maximum likelihood’ fails miserably,” Gaucher said.
But, now, a host of data and analysis give scientists a great picture of how evolution works (and it’s not a parsimony principle): For ages, nothing moves, then change bursts forth, then things stabilize again.
“You get this quick evolution, so lots of stuff works and lots of stuff fails, and the stuff that works then goes on and kind of maintains its status and doesn’t change,” Gaucher said. By confirming the high accuracy of the algorithms, the Georgia Tech team has also corroborated the validity of current evolutionary science they’re based on.
Kelsey Roof and Divya Natarajan of Georgia Tech coauthored the paper. Research was funded the NASA Exobiology program (grant number NNX12AI10G), DuPont (Young Professor Award) and the National Science Foundation (grant number 1145698). 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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