Jeffrey Skolnick, Ph.D., Mary and Maisie Gibson Chair and Georgia Research Alliance Eminent Scholar in Computational Systems Biology at Georgia Tech, will receive the Southeastern Universities Research Association’s (SURA) 2014 Distinguished Scientist Award. The award is given annually to a scientist whose extraordinary work fulfills the society’s mission of “fostering excellence in scientific research.”
Skolnick, who also serves as Director of the Integrative BioSystems Institute, will be presented the award and its $10,000 honorarium on March 18, 2014 at the SURA Board of Trustees meeting at the University of West Virginia at the SURA’s spring board of trustee’s meeting.
“Jeff is extremely deserving of this award as he is one of the outstanding thought leaders in the field and has been called ‘visionary’ and ‘an out of the box thinker’ by many colleagues,” stated Mark Hay, Ph.D., professor and Harry and Linda Teasley Chair in Environmental Biology in the School of Biology at Georgia Tech. “Not only has his research provided unique and fundamental insights into the behavior of biological systems, he has developed several of the best algorithms for virtual ligand screening and for predicting protein structure-function relationships.”
Skolnick is the author or co-author of over 350 journal articles in the fields of systems and computational biology and his cutting edge research on protein structure and function has provided remarkable insights into the relative roles of physics and evolution in dictating the properties of protein structure and function and holds the potential to dramatically accelerate and enhance the drug discovery process.
“Jeff is a world-class scientist with tremendous imagination and creativity,” stated Terry Snell, Chair of the School of Biology at Georgia Tech. “His research has significantly enhanced our understanding of protein structure and function.”
Over his career, Skolnick has made significant scientific contributions. He developed the first coarse grained model for protein structure prediction, the first successful multiscale modeling approach to structure prediction, the first effective medium model for a membrane that enabled the successful prediction of peptide orientation and conformation with respect to the membrane, Fuzzy Functional Forms that were the first low resolution approach to protein function prediction, and the highly accurate EFICAz approach to enzyme function inference. His more recent work has significant applications to both drug discovery and to improving our fundamental understanding of the possible origin of life.
The SURA Distinguished Scientist Award was established in 2007 to commemorate the organization’s 25th Anniversary and is considered its highest honor. SURA’s Development & Relations Committee manages the solicitation, screening and selection of the recipient for this award from a SURA member institution.
By inferring and resurrecting ancient sequences for an enzyme called uricase, the group was able to determine when and why the enzyme stop functioning in apes (including humans) while remaining functional in most other mammals. See the following link for an insightful article written by National Geographic: http://phenomena.nationalgeographic.com/2014/02/17/a-resurrected-cretaceous-answer-to-the-disease-of-kings/
Congratulations to the following faculty and staff members who were honored at the 2014 Faculty and Staff Honors Luncheon on April 11.
Georgia Tech Chapter Sigma Xi Awards
Young Faculty Awards
Satish Kumar, Mechanical Engineering
Christopher Rozell, Electrical and Computer Engineering
Sustained Research Award
C.F. Jeff Wu, Industrial and Systems Engineering
Institute Research Awards
Outstanding Achievement in Research Enterprise Enhancement
Mary Hallisey Hunt, Strategic Energy Institute
Outstanding Achievement in Research Innovation
Mark Prausnitz, Chemical and Biomolecular Engineering
Outstanding Doctoral Thesis Advisor
John Cressler, Electrical and Computer Engineering
Outstanding Faculty Leadership for the Development of Graduate Research Assistants
Kenneth Sandhage, Materials Science and Engineering
Outstanding Faculty Research Author
Seth Marder, Chemistry and Biochemistry
Outstanding Achievement in Research Program Development
Gang Bao, Biomedical Engineering
Christine Valle, College of Engineering
Outstanding Staff Performance Awards
Phyllis Means, Office of the Executive Vice President for Research
David Knobbe and Matthew Marcus, Campus Recreation Center
D. Matthew Watkins, Georgia Tech Police Department
Dustin Hamilton, Campus Recreation Center
Stephanie Ray, Dean of Students
Outstanding Management in Action Award
Marc Pline, Biology
Administrative Excellence Award
David Williams, Campus Recreation Center
Undergraduate Educator Awards
Michael Rodgers, Civil and Environmental Engineering
Chrissy Spencer Biology
Innovation and Excellence in Laboratory Instruction Award
Essy Behravesh, Biomedical Engineering
CETL/BP Junior Faculty Teaching Excellence Awards
J. Brandon Dixon, Mechanical Engineering
Flavio Fenton, Physics
Brian Hammer, Biology
Kamran Paynabar, Industrial and Systems Engineering
Anne Pollock, Literature, Media, and Communication
Kari E. Watkins, Civil and Environmental Engineering
Education Partnership Awards
Eric Gaucher, School of Biology
Ryan Randall, School of Biology
Curriculum Innovation Award
Amy Pritchett, Aerospace Engineering
Innovation in Co-Curricular Education Award
Jennifer Leavey, College of Sciences
Faculty Award for Academic Outreach
Stefan France, Chemistry and Biochemistry
Eichholz Faculty Teaching Awards
Linda Green, Biology
Donald Webster, Civil and Environmental Engineering
Steven A. Denning Faculty Award for Global Engagement
Michael Best, International Affairs
Academic Advisor Awards
Outstanding Undergraduate Academic Advising: Staff
Kim Paige, Biomedical Engineering
Outstanding Undergraduate Academic Advising: Faculty
Linda Green, Biology
Faculty Honors Committee Awards
Outstanding Undergraduate Research Mentor (Faculty) Award
Margaret Kosal, International Affairs
Kenneth Gall, Materials Science and Engineering
Outstanding Professional Education Award
A.P. Sakis Meliopoulos, Electrical and Computer Engineering
Outstanding Service Award
Michael Hunter, Civil and Environmental Engineering
Class of 1934 Outstanding Innovative Use of Education Technology Award
James Hamblen, Electrical and Computer Engineering
Class of 1934 Outstanding Interdisciplinary Activity Award
Bernard Kippelen, Electrical and Computer Engineering
Class of 1940 W. Howard Ector Outstanding Teacher Award
Joel Sokol, Industrial and Systems Engineering
Class of 1940 W. Roane Beard Outstanding Teacher
Mike Stilman, Interactive Computing
Class of 1934 Distinguished Professor Award
Zhong Lin Wang, Materials Science and Engineering
Monica’s research will focus on a systems biology approach towards the developing of a malaria vaccine. Using gene expression profiling of the human immune response to malaria vaccination, Monica hopes to investigate the safety and efficacy of vaccines, along with the most effective strategies of vaccine implementation. The Schlumberger Foundation is a prestigious foundation, which selects outstanding women from developing counters to aid in their pursuit of graduate studies in engineering, science and technology disciplines worldwide. Grant recipients are selected both for their leadership capabilities and scientific talents. Ultimately they are expected to return to their home country’s to become inspiration role models and disseminate the information gained during their studies. Monica is from Colombia and her research has direct impact into her home country, as malaria is one of the major public health problems of the tropics.
Fish living on coral reefs where carbon dioxide seeps from the ocean floor were less able to detect predator odor than fish from normal coral reefs, according to a new study.
The study confirms laboratory experiments showing that the behavior of reef fishes can be seriously affected by increased carbon dioxide concentrations in the ocean. The new study is the first to analyze the sensory impairment of fish from CO2 seeps, where pH is similar to what climate models forecast for surface waters by the turn of the century.
"These results verify our laboratory findings," said Danielle Dixson, an assistant professor in the School of Biology at the Georgia Institute of Technology in Atlanta. "There's no difference between the fish treated with CO2 in the lab in tests for chemical senses versus the fish we caught and tested from the CO2 reef."
The research was published in the April 13 Advance Online Publication of the journal Nature Climate Change. Philip Munday, from James Cook University in Australia, was the study's lead author. The work was supported by the Australian Institute for Marine Science, a Grant for Research and Exploration by the National Geographic Society, and the ARC Centre of Excellence for Coral Reef Studies.
The pH of normal ocean surface water is around 8.14. The new study examined fish from so-called bubble reefs at a natural CO2 seep in Papua New Guinea, where the pH is 7.8 on average. With today's greenhouse gas emissions, climate models forecast pH 7.8 for ocean surface waters by 2100, according to theIntergovernmental Panel on Climate Change (IPCC).
"We were able to test long-term realistic effects in this environment," Dixson said. "One problem with ocean acidification research is that it's all laboratory based, or you're testing something that's going to happen in a 100 years with fish that are from the present day, which is not actually accurate."
Previous research had led to speculation that ocean acidification might not harm fish if they could buffer their tissues in acidified water by changing their bicarbonate levels. Munday and Dixson were the first to show that fishes' sensory systems are impaired under ocean acidification conditions in the laboratory.
"They can smell but they can't distinguish between chemical cues," Dixson said.
Carbon dioxide released into the atmosphere is absorbed into ocean waters, where it dissolves and lowers the pH of the water. Acidic waters affect fish behavior by disrupting a specific receptor in the nervous system, called GABAA, which is present in most marine organisms with a nervous system. When GABAA stops working, neurons stop firing properly.
Coral reef habitat studies have found that CO2-induced behavioral changes, similar to those observed in the new study, increase mortality from predation by more than fivefold in newly settled fish.
Fish can smell a fish that eats another fish and will avoid water containing the scent. In Dixson's laboratory experiments, control fish given the choice between swimming in normal water or water spiked with the smell of a predator will choose the normal water. But fish raised in water acidified with carbon dioxide will choose to spend time in the predator-scented water.
Juvenile fish living at the carbon dioxide seep and brought onto a boat for behavior testing had nearly the identical predator sensing impairment as juvenile fish reared at similar CO2 levels in the lab, the new study found.
The fish from the bubble reef were also bolder. In one experiment, the team measured how far the fish roamed from a shelter and then created a disturbance to send the fish back to the shelter. Fish from the CO2 seep emerged from the shelter at least six times sooner than the control fish after the disturbance.
Despite the dramatic effects of high CO2 on fish behaviors, relatively few differences in species richness, species composition and relative abundances of fish were found between the CO2 seep and the control reef.
"The fish are metabolically the same between the control reef and the CO2 reef," Dixson said. "At this point, we have only seen effects on their behavior."
The researchers did find that the number of large predatory fishes was lower at the CO2 seep compared to the control reef, which could offset the increased risk of mortality due to the fishes' abnormal behavior, the researchers said.
In future work, the research team will test if fish could adapt or acclimate to acidic waters. They will first determine if the fish born at the bubble reef are the ones living there as adults, or if baby fish from the control reef are swimming to the bubble reef.
"Whether or not this sensory effect is happening generationally is something that we don't know," Dixson said.
The results do show that what Dixson and colleagues found in the lab matches with what is seen in the field.
"It's a step in the right direction in terms of answering ocean acidification problems." Dixson said. "The alternative is just to wait 100 years. At least now we might prepare for what might be happening."
This research is supported by the Australian Institute for Marine Science, a Grant for Research and Exploration by the National Geographic Society, and the ARC Centre of Excellence for Coral Reef Studies. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agencies.
CITATION: Philip L. Munday, et al., "Behavioural impairment in reef fishes caused by ocean acidification at CO2 seeps." (Nature Climate Change, April 2014). http://dx.doi.org/10.1038/NCLIMATE2195
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Writer: Brett Israel
From time to time, living cells will accidently make an extra copy of a gene during the normal replication process. Throughout the history of life, evolution has molded some of these seemingly superfluous genes into a source of genetic novelty, adaptation and diversity. A new study shows one way that some duplicate genes could have long-ago escaped elimination from the genome, leading to the genetic innovation seen in modern life.
Researchers have shown that a process called DNA methylation can shield duplicate genes from being removed from the genome during natural selection. The redundant genes survive and are shaped by evolution over time, giving birth to new cellular functions.
“This is the first study to show explicitly how the processes of DNA methylation and duplicate gene evolution are related,” said Soojin Yi, an associate professor in the School of Biology and the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology.
The study was sponsored by the National Science Foundation (NSF) and was scheduled to be published the week of April 7 in the Online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS).
At least half of the genes in the human genome are duplicates. Duplicate genes are not only redundant, but they can be bad for cells. Most duplicate genes accumulate mutations at high rates, which increases the chance that the extra gene copies will become inactive and lost over time due to natural selection.
The new study found that soon after some duplicate genes form, small hydrocarbons called methyl groups attach to a duplicate gene’s regulatory region and block the gene from turning on.
When a gene is methylated, it is shielded from natural selection, which allows the gene to hang around in the genome long enough for evolution to find a new use for it. Some young duplicate genes are silenced by methylation almost immediately after being formed, the study found.
“What we have done is the first step in the process to show that young gene duplicates seems to be heavily methylated,” Yi said.
The study showed that the average level of DNA methylation on the duplicate gene regulatory region is significantly negatively correlated with evolutionary time. So, younger duplicate genes have high levels of DNA methylation.
For about three-quarters of the duplicate gene pairs studied, the gene in a pair that was more methylated was always more methylated across all 10 human tissues studied, said Thomas Keller, a post-doctoral fellow at Georgia Tech and the study’s first author.
“For the tissues that we examined, there was remarkable consistency in methylation when we looked at duplicate gene pairs,” Keller said.
The computational study constructed a dataset of all human gene duplicates by comparing each sequence against every other sequence in the human genome. DNA methylation data was then obtained for the 10 different human tissues. The researchers used computer models to analyze the links between DNA methylation and gene duplication.
The human brain is one example of a tissue for which gene duplication has been particularly important for its evolution. In future studies, the researchers will examine the link between epigenetic evolution and human brain evolution.
This research is supported by the National Science Foundation (NSF) under award numbers BCS-1317195 and MCB-0950896. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agency.
CITATION: Thomas E. Keller, et al., “DNA Methylation and Evolution of Duplicate Genes.” (PNAS, April 2014). http://www.dx.doi.org/10.1073/pnas.1321420111
Georgia Institute of Technology
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Writer: Brett Israel
Populations of predators and their prey usually follow predictable cycles. When the number of prey increases, perhaps as their food supply becomes more abundant, predator populations also grow.
When the predator population becomes too large, however, the prey population often plummets, leaving too little food for the predators, whose population also then crashes. This canonical view of predator-prey relationships was first identified by mathematical biologists Alfred Lotka and Vito Volterra in the 1920s and 1930s.
But all bets are off if both the predator and prey species are evolving in even small ways, according to a new study published this week in the journal Proceedings of the National Academy of Sciences. When both species are evolving, the traditional cycle may reverse, allowing predator populations to peak before those of the prey. In fact, it may appear as if the prey are eating the predators.
Researchers at the Georgia Institute of Technology have proposed a theory to explain these co-evolutionary changes. And then, using data collected by other scientists on three predator-prey pairs – mink-muskrat, gyrfalcon-rock ptarmigan and phage-Vibrio cholerae – they show how their theory could explain unexpected population cycles.
The new theory and analysis of these co-evolution cycles could help epidemiologists predict cycles of disease and the virulence of infectious agents, and lead to a better understanding of how population cycles may affect ecosystems. The research was supported by the National Science Foundation and the Burroughs Wellcome Fund.
“Our work shows that co-evolution can yield new and unique behavior at the population scale,” explained Joshua Weitz, an associate professor in the School of Biology at Georgia Tech. “When you include evolution, the classic prey-predator dynamics have a much greater range of possible outcomes. We are not replacing the original theory, but proposing a more general model that opens the door to these new phenomena.”
Evolution is often perceived as an historical event, noted Weitz, who also has a courtesy appointment in the Georgia Tech School of Physics. But organisms are evolving continuously, with certain phenotypes becoming dominant as environmental and other conditions favor them. In organisms such as birds or small mammals, those changes can be manifested in as few as ten generations. In microbial species with brief lifespans, evolutionary changes can happen within days or weeks.
Evolutionary changes can dramatically affect relationships between species, potentially making them more vulnerable or less vulnerable. For instance, if a mutation that confers viral resistance in a species of bacteria becomes dominant, that may change the predator-prey relationship by rendering the bacteria population safe from harm. More generally, co-evolutionary cycles can arise when predator offense is costly and prey defense is effective against low offense predators.
“With predator and prey co-evolution, you can see oscillations in which there are lots of prey around even when there are many predators, or lots of predators around even when there are very few prey,” noted Michael Cortez, a postdoctoral fellow in the Weitz lab and first author of the paper.
“When prey is abundant and there are few predators, it may be because there are many defended prey – prey that the predators can’t eat,” he added. “When there are lots of predators around and few prey, it’s because the prey are very good food sources and the predators are doing quite well.”
In their paper, Weitz and Cortez simulated models in which the evolutionary process was sped up to show how their theory of co-evolution would affect predator-prey population cycles. Speeding up the process allowed them to break the cycle up into smaller segments that could be analyzed in more detail. They then used the earlier observations of the changing abundances of the three pairs of predators and prey -- leveraging data sets collected by other scientists – to show how the models would apply.
“Although the structure of the cycles in these three systems had been noted as unusual by the authors who observed them, there had been, as yet, no unified theoretical framework from which to make sense of such as radical departure from the classic signature of predator-prey interactions,” Weitz said.
Scientists have long studied how the interaction between species affects overall populations in ecosystems. Weitz and Cortez believe their new model will give scientists a broader and more complete picture of the complex process.
“This study identifies how adaptation between two species and interactions between their numbers can result in something different from what you would get if you just had the interaction between the numbers,” said Cortez. “This is something that will show up across many ecological systems. We can now explain broad trends that occur in vastly different systems using a theoretical approach, and the fact that we can identify the mechanism responsible for it is unique to our study.”
This research was supported by the National Science Foundation under Award DMS-1204401, and by the Burroughs Wellcome Fund. Any conclusions or opinions expressed are those of the authors and do not necessarily represent the official views of the sponsoring agencies.
CITATION: Michael H. Cortez and Joshua S. Weitz, “Coevolution Can Reverse Predator-Prey Cycles,” (Proceedings of the National Academy of Sciences, 2014). www.pnas.org/cgi/doi/10.1073/pnas.1317693111
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Writer: John Toon
A study of 338 patients with coronary artery disease has identified a gene expression profile associated with an elevated risk of cardiovascular death. Used with other indicators such as biochemical markers and family history, the profile – based on a simple blood test – may help identify patients who could benefit from personalized treatment and counseling designed to address risk factors.
Researchers found the risk signature by comparing gene expression profiles in 31 study subjects who died of cardiovascular causes against the profiles of living members of the study group. Twenty-five of the 31 deaths occurred in the group with the high-risk profile, though coronary deaths were also recorded among the lower risk members of the study group. All of the patients studied had coronary artery disease (CAD), and about one in five had suffered a heart attack prior to the study.
Researchers from the Georgia Institute of Technology, Emory University and Princeton University participated in the study, which obtained gene expression profiles from blood samples taken from patients undergoing cardiac catheterization at Emory University clinics in Atlanta. The results were published in the open-access journal Genome Medicine on May 29, 2014.
“We envision that with our gene expression-based marker, plus some biochemical markers, genotype information and family history, we could produce a tiered evaluation of people’s risks of adverse coronary events,” said Gregory Gibson, director of the Center for Integrative Genomics at Georgia Tech and one of the study’s senior authors. “This could lead to a personalized medicine approach for people recovering from heart attack or coronary artery bypass grafting.”
Coronary artery disease is the leading cause of death for both men and women in the United States. Manifested in the narrowing of blood vessels through the buildup of plaque, CAD sets the stage for heart attacks and long-term heart failure.
As many as half of Americans over the age of 50 suffer from CAD to some extent, so the researchers wondered if they could single out those with the highest risk of death. From a cohort of more than 3,000 persons known as the Emory Cardiovascular Biobank (EmCD), they selected two groups of patients for extensive gene expression analysis based on blood samples.
After following the patients for as long as five years, the researchers examined gene expression patterns in a total of 31 persons from the study group who had suffered coronary deaths. Comparing these patterns against those of other study subjects revealed a pattern in which genes affecting inflammation were up-regulated, while genes affecting T-lymphocytes were down-regulated.
The patients studied ranged in age from 51 to 73, were mostly Caucasian, and 65 percent male. Seventy percent of the subjects had significant CAD, and 18 percent were experiencing an acute myocardial infarction when blood samples were taken. Gene expression was analyzed using microarrays and two different normalization procedures to control for technical and biological covariates. Whole genome genotyping was used to support comparative genome-wide association studies of gene expression. Two phases of the study were conducted independently with the two different groups, and produced similar results.
“What’s new in this research is the recognition that this risk pathway exists and that it relates to particular aspects of immune system functions that include T-cell signaling,” said Gibson, who is also a professor in Georgia Tech’s School of Biology. “We went beyond the signature of coronary artery disease to really provide a signature for adverse outcomes in that high-risk population.”
The pattern, said Gibson, doesn’t indicate the causes of the disease. The researchers would now like to expand the study to include a larger group of patients and learn more about what causes the disease. They’d also like to know whether the risks can be reversed through diet, exercise or drug therapy.
Cardiologist Arshed Quyyumi, the paper’s other senior author, directs Emory University’s Clinical Cardiovascular Research Center and created the Biobank five years ago to facilitate cardiovascular research. He says that identifying patients at highest risk could help encourage their compliance with treatment programs, and prioritize introduction of newer therapeutics, such as cholesterol lowering medications like PCSK9 inhibitors.
“A number of patients with CAD are currently not maximally treated,” said Quyyumi, who is a professor in Emory’s School of Medicine. “In those that appear to have been prescribed adequate medication, a significant proportion of subjects are non-compliant with their medications. Thus, knowledge of a high risk genetic profile in a patient can prompt both the patient and physician to maximize currently available medications and improve patient compliance.”
Approximately 15,000 genes are expressed in human blood, but analyzing them is not as daunting as it sounds. Most of the gene expression is correlated, so there may be only a few dozen independent measurements that can be related to disease states, Gibson said. In the study, researchers identified nine “axes” that represented specific biological pathways to disease. Two of them were relevant to the high-risk profile.
Gibson believes identifying the high-risk signatures in CAD patients may lead to opportunities for improving their health.
“Our dream would be a hand-held device that would allow patients to take a droplet of blood, much like diabetics do today, and obtain an evaluation of these transcripts that they could track at home,” he said. “If we can use this information to help people adopt healthier behaviors, it will be very positive.”
In addition to those already mentioned, the co-authors include Jinhee Kim, from the Georgia Tech School of Biology; Nima Ghasemzadeh and Danny Eapen from the Emory University School of Medicine, and John Storey and Neo Christopher Chung from the Lewis-Sigler Institute at Princeton University.
CITATION: Jinhee Kim, Nima Ghasemzadeh, Danny J. Eapen, Neo Christopher Chung, John D. Storey, Arshed A. Quyyumi and Greg Gibson, “Gene expression profiles associated with acute myocardial infarction and risk of cardiovascular death.” (Genome Medicine 2014). http://genomemedicine.com/content/6/5/40.
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Writer: John Toon
New research reveals how the algae behind red tide thoroughly disables – but doesn’t kill – other species of algae. The study shows how chemical signaling between algae can trigger big changes in the marine ecosystem.
Marine algae fight other species of algae for nutrients and light, and, ultimately, survival. The algae that cause red tides, the algal blooms that color blue ocean waters red, carry an arsenal of molecules that disable some other algae. The incapacitated algae don’t necessarily die, but their growth grinds to a halt. This could explain part of why blooms can be maintained despite the presence of competitors.
In the new study, scientists used cutting-edge tools in an attempt to solve an old ecological mystery: Why do some algae boom and some algae bust? The research team used cultured strains of the algae that cause red tide, exposed competitor algae to its exuded chemicals, and then took a molecular inventory of the competitor algae’s growth and metabolism pathways. Red tide exposure significantly slowed the competitor algae’s growth and compromised its ability to maintain healthy cell membranes.
“Our study describes the physiological responses of competitors exposed to red tide compounds, and indicates why certain competitor species may be sensitive to these compounds while other species remain relatively resistant,” said Kelsey Poulson-Ellestad, a former graduate student at the Georgia Institute of Technology, now at Woods Hole Oceanographic Institution, and the study’s co-first author, along with Christina Jones, a Georgia Tech graduate student. “This can help us determine mechanisms that influence species composition in planktonic communities exposed to red tides, and suggests that these chemical cues could alter large-scale ecosystem phenomena, such as the funneling of material and energy through marine food webs.”
The study was sponsored by the National Science Foundation and was published June 2 in the Online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS). The work was a collaboration between Georgia Tech, the University of Washington, and the University of Birmingham in the United Kingdom.
The algae that form red tide in the Gulf of Mexico are dinoflagellates called Karenia brevis, or just Karenia by scientists. Karenia makes neurotoxins that are toxic to humans and fish. Karenia also makes small molecules that are toxic to other marine algae, which is what the new study analyzed.
“In this study we employed a global look at the metabolism of these competitors to take an unbiased approach to ask how are they being affected by these non-lethal, subtle chemicals that are released by Karenia,” said Julia Kubanek, Poulson-Ellestad’s graduate mentor and a professor in the School of Biology and the School of Chemistry and Biochemistry at Georgia Tech. “By studying both the proteins and metabolites, which interact to form metabolic pathways, we put together a picture of what’s happening inside the competitor algal cells when they’re extremely stressed.”
The research team used a combination of mass spectrometry and nuclear magnetic resonance spectroscopy to form a holistic picture of what’s happening inside the competitor algae. The study is the first time that metabolites and proteins were measured simultaneously to study ecological competition.
"A key aspect of this study was the use of high-resolution metabolomic tools based on mass spectrometry," said Facundo M. Fernández, a professor in the School of Chemistry and Biochemistry, whose lab ran the mass spectrometry analysis. "This allowed us to detect and identify metabolites affected by exposure to red tide microorganisms.”
Mass spectrometry was also used for analysis of proteins, an approach called proteomics, led by Brook Nunn at the University of Washington.
The research team discovered that red tide disrupts multiple physiological pathways in the competitor diatom Thalassiosira pseudonana. Red tide disrupted the energy metabolism and cellular protection mechanisms, inhibited their ability to regulate fluids and increased oxidative stress. T. pseudonana exposed to red tide toxins grew 85 percent slower than unexposed algae.
“This competitor that’s being affected by red tide is suffering a globally upset state,” Kubanek said. “It’s nothing like what it would be in a healthy, normal cell.”
The work shows that chemical cues in the plankton have the potential to alter large-scale ecosystem processes including primary production and nutrient cycling in the ocean.
The research team found that another competitor diatom, Asterionellopsis glacialis, which frequently co-occurs with Karenia red tides, was partially resistant to red tide, suggesting that co-occurring species may have evolved partial resistance to red tide via robust metabolic pathways.
Other work in Kubanek’s lab is examining red tide and its competition in the field to see how these interactions unfold in the wild.
“Karenia is a big mystery. It has these periodic blooms that happen most years now, but what’s shaping that cycle is unclear,” Kubanek said. “The role of competitive chemical cues in these interactions is also not well understood.”
This research is supported by the National Science Foundation under award number OCE-1060300. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agency.
CITATION: Kelsey L. Poulson-Ellestad, et al., “Metabolomics and proteomics reveal impacts of chemically mediated competition on marine plankton.” (June, PNAS) www.pnas.org/cgi/doi/10.1073/pnas.1402130111
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Writer: Brett Israel
To test whether the presence of RNA in DNA duplexes could alter the elasticity and structure of DNA, a group of researchers at Georgia Tech and Georgia State University, inspired by Francesca Storici, and including the labs of Elisa Riedo, Angelo Bongiorno and Markus Germann conducted a multidisciplinary study at the interface of physics, chemistry and molecular biology. The group employed atomic force microscopy (AFM)-based single molecule force-measurements of short rNMP(s)-containing oligonucleotides in combination with molecular dynamics (MD) simulations and nuclear magnetic resonance (NMR).
Ribonucleotides (rNMPs), the units of RNA, are the most abundant non-canonical nucleotides found in genomic DNA. rNMPs, either not removed from Okazaki fragments during DNA replication or incorporated and scattered throughout the genome, pose a perturbation to the structure and a threat to the integrity of DNA. The instability of DNA is mainly due to the extra 2’-hydroxyl (OH) group of rNMPs which gives rise to local structural effects that may disturb various molecular interactions in cells. As a result of these structural perturbations by rNMPs, the elastic properties of DNA may also be affected.
DNA has unique mechanical properties that are crucial in many natural biochemical processes and play an important role in DNA-based nanotechnology applications. Despite demonstrations of their abundance and importance, no data exist in literature regarding elastic measurements and sequence-dependent structural distortions of DNA with isolated single rNMP intrusions. With the goal to bring insights on how rNMPs change elastic properties of DNA and its structure, the Georgia Tech team with Hsiang-Chih Chiu and Kyung Duk Koh, a postdoctoral fellow at the time in the lab of Elisa Riedo in the School of Physics, and a PhD candidate in the lab of Francesca Storici from the School of Biology, respectively, together with the graduate student Annie Lesiak from Angelo Bongiorno lab in the School of Physics and School of Chemistry and Biochemistry, and in collaboration with Markus Germann and his graduate student Marina Evich from the Department of Chemistry at Georgia State University, conducted an innovative, experimental and theoretical study utilizing two short DNA molecules containing isolated rNMP intrusions. Storici said: <<We examined and identified how the elasticity and structure of DNA are altered by the rNMP intrusions in the studied DNA sequences>>. AFM-based single molecule force spectroscopy demonstrated that rNMP intrusions in short DNA duplexes can decrease – by 32% – or slightly increase the stretch modulus of DNA depending on specific sequence contexts next to the rNMPs. In addition, MD simulations and NMR experiments indicated that rNMP inclusions locally change the torsional distortion of the sugar-phosphate backbone in DNA only when the rNMPs are in specific locations in the DNA sequence. Riedo concluded: <<Our work opens up the route to use AFM single molecules measurements to understand how defects and the base sequence can affect the elasticity of short DNA molecules>>.
The demonstrated ability of rNMPs to locally change DNA mechanical properties and structure may find applications in structural DNA nanotechnology and help understanding how such intrusions impact DNA biological functions. Overall, these findings open a new route for understanding how rNMPs may influence DNA structure, chemistry, and biology.
The study is just published as an article in the journal Nanoscale (accepted, 2014):
Chiu HC*, Koh KD*, Evich M, Lesiak AL, Germann MW, Bongiorno A, Riedo E, Storici F (2014)
RNA intrusions change DNA elastic properties and structure. Nanoscale, DOI: 10.1039/C4NR01794C; *equal contribution.
This project was supported by the Office of Basic Energy Sciences of the US Department of Energy (DE-FG02-06ER46293), the National Science Foundation (NSF)(CMMI-1100290 and DMR-0820382), the Samsung Advanced Institute of Technology and the NSF grant CHE-0946869, the Integrative Biosystems Institute grant IBSI-4, the Georgia Research Alliance grant R9028 and the NSF grant MCB-1021763.