The new Engineered Biosystems Building will be a giant leap forward in creating the infrastructure that inspires and sustains scientific discovery at Georgia Tech. EBB will enable us to expand our commitment to improving and saving lives by providing bringing new treatments, medical technologies, medications, and therapies to patients.  The key to innovation lies in collaboration, and the EBB is designed to facilitate research across disciplinary and institutional boundaries. Partnerships are integral to the success of EBB, especially between faculty from the Colleges of Sciences, Engineering, Computing, and between Georgia Tech researchers and those from Emory University, Children’s Healthcare of Atlanta, and other institutions. The research conducted in EBB will help distinguish Georgia Tech as a national leader in biomedicine and biotechnology.

EBB will provide 200,000 square feet of technologically advanced laboratories for faculty, researchers, and students to pursue Georgia Tech’s growing research agenda in the biological sciences. The building will also strengthen the Georgia Tech’s ability to attract and retain the best faculty from around the world. It will allow the College of Sciences to increase the size of its faculty in Biology over the next decade. In turn, these exceptional teacher-scholars will draw the brightest, most talented graduate students to Tech. Moreover, EBB will significantly enhance Georgia Tech’s commercialization efforts, stimulate job growth in the state, and generate new startup companies.

Gross-chromosomal rearrangements are a hallmark of cancers and hereditary diseases. On the other hand, these events can trigger the generation of polymorphisms and lead to evolution. The driving force behind chromosomal rearrangements is DNA double strand breaks. A variety of factors can contribute to the generation of breaks in the genome. A paradoxical source of breaks is the sequence composition of the genomic DNA itself. Eukaryotic and prokaryotic genomes contain sequence motifs capable of adopting secondary structures often found to be potent inducers of double strand breaks culminating into rearrangements. These regions are therefore termed fragile sequence motifs.

A recently published study authored by Natalie Saini and colleagues in the lab of Kirill Lobachev (School of Biology), demonstrates that two particular types of fragile sequence motif, inverted repeats and triplex-forming repeats, increase mutation frequency in surrounding DNA regions. Interestingly, repeat-induced mutagenesis was found to spread large distances on either side flanking the break-point and requires the activity of an error-prone DNA polymerase. Remarkably, repair of the induced double-strand break via homologous recombination, a process previously thought to be error-free, also yields mutations and reconstitutes the repeats. This discovery is the first demonstration that inverted repeats and triplex-forming repeats provide a long-term source of DNA breakage and mutagenic repair. Consequently, secondary structure-forming repeats are a dual threat to genome stability due to their inherent potential to induce both rearrangements and mutations in the flanking DNA regions.

The study was published in Public Library of Science (PLoS) Genetics on 13 June 2013 and can be found at: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003551. Funding for this research was provided by grants from the NSF and NIH to Kirill Lobachev.

By studying rapidly evolving bacteria as they diversify and compete under varying environmental conditions, researchers have shown that temporal niches are important to maintaining biodiversity in natural systems. The research is believed to be the first experimental demonstration of temporal niche dynamics promoting biodiversity over evolutionary time scales.

The temporal niches – changes in environmental conditions that occur during specific periods of time – promoted frequency-dependent selection within the bacterial communities and positive growth of new mutants. They played a vital role in allowing diversity among bacterial phenotypes to persist.

The research provides new insights into the factors that promote species coexistence and diversity in natural systems. Understanding the mechanisms governing the origin and maintenance of biodiversity is important to scientists studying the roles of both ecology and evolution in natural systems.

“This study provides the first experimental evidence showing the impact of temporal niche dynamics on biodiversity evolution,” said Lin Jiang, co-author of the paper and an associate professor in the School of Biology at the Georgia Institute of Technology. “Our laboratory results in bacteria can potentially explain the diversity dynamics that have been observed for other organisms over evolutionary time.”

The research, which was supported by the National Science Foundation, was published July 9 in the journal Nature Communications.

In experimental manipulation of the bacterium Pseudomonas fluorescens, the researchers showed that alternating environmental conditions in 24-hour cycles strongly influences biodiversity dynamics by helping to maintain closely-related phenotypes that might otherwise be lost to competition with a dominant phenotype. The experiment followed the bacteria through more than 200 generations over a period of nearly two weeks.

In the laboratory, Jiang and graduate student Jiaqi Tan established communities of the bacterium in test tubes called microcosms. In designing the experiments, they collaborated with Colleen Kelly, a senior research associate in the Department of Zoology at the University of Oxford.

“You begin with one phenotype, and within two days, you might have two or three different phenotypes,” said Jiang. “The system can do this in a matter of days.”

Through a 12-day experimental period, the researchers subjected one group of cultures to 24-hour periods in which they were alternately allowed to grow undisturbed and shaken vigorously. To control for the impact of starting conditions, cultures within those two groups were chosen to begin with a period of static growth, while others began with a period of shaken growth. Finally, groups of control cultures were grown under continuous shaking or continuous static conditions.

During the study, the researchers periodically measured the population sizes of each phenotype present in each culture. Cultures subjected to alternating shaking and static conditions produced the highest level of diversity among the closely-related bacteria, which is often studied because it diversifies so rapidly.

“Static conditions promoted diversification,” Jiang explained. “But the shaking tended to maintain the diversity that had evolved. Both conditions were essential for high biodiversity.”

In experiments, the ancestral bacterial phenotype, which is known as “smooth morph,” quickly diversifies and generates two niche-specialists, known as “wrinkled spreader” and “fuzzy spreader.” Those, in turn, diversify into additional phenotypes. Competition for oxygen in the microcosms in which the bacteria grow is believed to drive the diversification; shaking the microcosms changes the levels of oxygen available to each phenotype. Because different phenotype groups inhabit different sections of the container, the shaking eliminated the preferred niches of some phenotypes.

The diversification in the microcosms experiencing constant shaking was much slower than in static microcosms. In microcosms experiencing temporal niche dynamics – the alternating shaking and non-shaking periods – the diversity increased rapidly and was maintained longer than in the other environments. The researchers found that the two different temporal niche dynamics environments – which differed only in their starting conditions – both produced richer biodiversity than those environments without it.

While the diversification occurred rapidly over a period of four days, the decline in the number of phenotypes due to natural competition took longer. Some of the phenotypes were ultimately excluded through the competitive processes.

“Diversity typically increases with time, then plateaus,” said Jiang. “Without temporal niche, diversity tends to decline. Temporal niche allows a greater diversity to be maintained over time than would be possible otherwise.”

Though the study focused on rapidly diversifying bacteria, the researchers believe it may have broader implications. The general theory of temporal niche dynamics was developed with more complex organisms, such as plants and corals, in mind.

“The mechanisms that promote biodiversity, which we call frequency-dependent selection, are very common in species,” said Tan. “As long as you have a strong intra-species competition within the populations, you are expected to see this frequency-dependent selection. Based on this most common mechanism that we find in this system, there are implications for other ecosystems.”

For the future, the researchers would like to study the effects of combining spatial and temporal niches in evolution.

“From this experiment, we know that temporal niche can maintain biodiversity,” said Tan. “Similarly, we want to manipulate spatial diversity to see if heterogeneity in the spatial scale can affect the maintenance of biodiversity.”

This research was supported by the National Science Foundation under grants DEB-1120281 and DEB-1257858. Any opinions expressed are those of the authors and do not necessarily represent the official views of the National Science Foundation.

CITATION: Jiaqi Tan, Colleen K. Kelly and Lin Jiang, “Temporal niche promotes biodiversity during adaptive radiation,” (Nature Communications, 2013). http://dx.doi.org/10.1038/ncomms3102

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Media Relations Contact: John Toon (404-894-6986)(jtoon@gatech.edu).

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The bacterium Vibrio cholerae annually causes millions of cases of the often fatal disease cholera, typically in regions where access to clean drinking water is limited. V. cholerae can be introduced into water by infected individuals who can sometimes be asymptomatic, however this microbe is also a natural inhabitant of aquatic waters. Since the summer following the tragic January 2010 earthquake in Haiti, an on-going cholera epidemic has resulted in more than 600,000 individual cases and 7,500 deaths. The emergence of this cholera epidemic has sparked questions as to whether the origin of the outbreak was imported or indigenous. Previous genome sequencing studies suggested that a strain of V. cholerae was inadvertently introduced into Haiti by United Nations security forces deployed from Nepal, where cholera outbreaks occurred weeks before the troops were deployed to the island. Subsequent studies, however, suggest that the strain may have acquired DNA through “horizontal gene transfer” from other Vibrio organisms in the local environmental – a phenomenon that may have contributed to the outbreak.

In a new study published in the journal mBio, the Centers for Disease Control and Prevention’s Cheryl Tarr and Lee Katz  (School of Biology Ph.D. recipient) along with Georgia Tech’s School of Biology Professor Brian Hammer, his student Elena Antonova, and other colleagues, analyzed a set of isolates collected in Haiti at various times and locations since 2010. Genome sequencing of these isolates supports a model in which the outbreak was due to a single point-source introduction of V. cholerae to the island. Further analysis revealed that not only have the Haiti isolates not acquired new genes from the environment, but they are also severely impaired for the ability to undergo horizontal gene transfer, which typically allows bacteria to adapt quickly to new environments. On-going studies are underway to identify the mutation that prevents the Haiti strains from taking up environmental DNA.

The study was published on July 2, 2013 in mBio, the online open access journal from the American Society for Microbiology, and can be found at: http://mbio.asm.org/content/4/4/e00398-13. Funding for Hammer’s work in this study was provided by a grant from the National Science Foundation.

Patrick McGrath, an Assistant Professor in the School of Biology, has been chosen as an Ellison Medical Foundation New Scholar in Aging (http://www.ellisonfoundation.org/program/aging-new-scholar) to study how complex genetics can influence the aging process in the small nematode C. elegans. Dr. McGrath joined the School of Biology in 2012.

In humans, lifespan is a heritable trait, meaning that differences in our genes influence how fast we age. The McGrath lab plans to identify new signaling pathways controlling aging that are preferentially modified by combinations of natural polymorphisms segregating within a population.

The foundation’s New Scholar awards provide support for new investigators to help establish their labs. The award provides funding of $100,000 per year for a four-year period.

New Scholar applications are by invitation only. This is the first year that Georgia Tech has been invited to nominate a candidate to apply.

More information about McGrath lab research can be found at http://mcgrathlab.biology.gatech.edu.

For the majority of cancer patients, it’s not the primary tumor that is deadly, but the spread or “metastasis” of cancer cells from the primary tumor to secondary locations throughout the body that is the problem. That’s why a major focus of contemporary cancer research is how to stop or fight metastasis.

Previous lab studies suggest that metastasizing cancer cells undergo a major molecular change when they leave the primary tumor – a process called epithelial-to-mesenchymal transition (EMT). As the cells travel from one site to another, they pick up new characteristics. More importantly, they develop a resistance to chemotherapy that is effective on the primary tumor. But confirmation of the EMT process has only taken place in test tubes or in animals.

In a new study, published in the Journal of Ovarian Research, Georgia Tech scientists have direct evidence that EMT takes place in humans, at least in ovarian cancer patients. The findings suggest that doctors should treat patients with a combination of drugs: those that kill cancer cells in primary tumors and drugs that target the unique characteristics of cancer cells spreading through the body.

The researchers looked at matching ovarian and abdominal cancerous tissues in seven patients. Pathologically, the cells looked exactly the same, implying that they simply fell off the primary tumor and spread to the secondary site with no changes. But on the molecular level, the cells were very different. Those in the metastatic site displayed genetic signatures consistent with EMT. The scientists didn’t see the process take place, but they know it happened.

“It’s like noticing that a piece of cake has gone missing from your kitchen and you turn to see your daughter with chocolate on her face,” said John McDonald, director of Georgia Tech’s Integrated Cancer Research Center and lead investigator on the project. “You didn’t see her eat the cake, but the evidence is overwhelming. The gene expression patterns of the metastatic cancers displayed gene expression profiles that unambiguously identified them as having gone through EMT.”

The EMT process is an essential component of embryonic development and allows for reduced cell adhesiveness and increased cell movement.

According to Benedict Benigno, collaborating physician on the paper, CEO of the Ovarian Cancer Institute and director of gynecological oncology at Atlanta’s Northside Hospital, “These results clearly indicate that metastasizing ovarian cancer cells are very different from those comprising the primary tumor and will likely require new types of chemotherapy if we are going to improve the outcome of these patients.”

Ovarian cancer is the most malignant of all gynecological cancers and responsible for more than 14,000 deaths annually in the United States alone. It often reveals no early symptoms and isn’t typically diagnosed until after it spreads.

“Our team is hopeful that, because of the new findings, the substantial body of knowledge that has already been acquired on how to block EMT and reduce metastasis in experimental models may now begin to be applied to humans,” said Georgia Tech graduate student Loukia Lili, co-author of the study.

Welcome to a new year at Georgia Tech. Now that you’re back, it’s time to start thinking about studying abroad. Yes, you just got here, but since you’re at Georgia Tech, that means you think ahead and plan, so come to the open house at the Office of International Education this Wednesday from 11 am - 1 pm on the second floor of the Savant Building and start planning to see the world.

One student who’s seen the world is Bibiana “Bibi” Garcia. She’s starting her fifth year at Georgia Tech with a major in biology. She was born and raised in South America, but moved to Augusta, Ga when she began high school. Having lived in various countries, it was, perhaps, natural for her to want to study abroad. But she keeps doing it because she loves learning and says she learns something new in each place she visits.

“Traveling to a different country on your own is an excellent opportunity to do something outside of your comfort zone and challenge yourself so that you can grow as a person,” said Garcia.

Lorie Paulez, director of education abroad in Tech’s Office of International Education said that it’s not only about challenging yourself, but it’s about setting yourself up for a better career.

“We are finding more and more employers looking for graduates that have international experience these days,” said Paulez. “Because having gone abroad and having to learn to function in a culture that’s not your own gives you special skills and shows a certain amount of adaptability, flexibility and problem solving skills.”

Some students just go abroad once during their time at Tech, while others, like Garcia, go on multiple trips. Her first study abroad experience came in 2011 with the three-month Pacific Program where the group went to Wellington, New Zealand; Sydney, Australia and Brisbane, Australia. This past year, she returned to Sydney for a five-month exchange program with the University of New South Wales for a more in-depth experience.

“My philosophy is to look at my life and experience each day,” said Garcia. “I try to learn as much as I can from those around me and take advantage of every opportunity and experience available to me.”

Tech has a number of study abroad experiences available, said Paulez. There are the traditional summer study programs, but there are also exchange programs, like the one Garcia attended in Sydney, where students spend a semester or two abroad. Either of these programs may offer a research component, or service opportunities.

And knowing another language before you go isn’t necessary for all programs.

“We have options for everyone,” said Paulez. “Sometimes we have students who have already been studying a language, or a particular place or culture and they want to enhance that. But we also have students who have never been out of the United States and don’t speak another language.”

Interested in learning more? Then go to the Study Abroad Open House on Wednesday to get all your burning questions answered.

Elizabeth McMillan, working in the Kubanek Lab, was awarded the top presentation award at the Undergraduate Research Kaleidoscope event this week.  Elizabeth studies chemically mediated competition specific to the red tide, Karenia brevis.  Her presentation focused on examining the variation in the response of algal competitors from two different marine communities to chemicals released by K. brevis. 

Well Done!

Researchers have discovered the details of how cells repair breaks in both strands of DNA, a potentially devastating kind of DNA damage.

When chromosomes experience double-strand breaks due to oxidation, ionizing radiation, replication errors and certain metabolic products, cells utilize their genetically similar chromosomes to patch the gaps via a mechanism that involves both ends of the broken molecules. To repair a broken chromosome that lost one end, a unique configuration of the DNA replication machinery is deployed as a desperation strategy to allow cells to survive, the researchers discovered.

The collaborative work of graduate students working under Anna Malkova, associate professor of biology at Indiana University-Purdue University Indianapolis (IUPUI) and Kirill Lobachev, associate professor of biology at the Georgia Institute of Technology, was critical in the advancement of the project. The group’s research was scheduled to be published Sept. 11 in the online edition of the journal Nature, with two graduate students, Sreejith Ramakrishnan of IUPUI, and Natalie Saini of Georgia Tech, as first authors. Other collaborators include James Haber of Brandeis University and Grzegorz Ira of the Baylor College of Medicine.

“Previously we have shown that the rate of mutations introduced by break-induced replication is 1,000 times higher as compared to the normal way that DNA is made naturally, but we never understood why,” Malkova said.

Lobachev’s lab used cutting-edge analysis techniques and equipment available at only a handful of labs around the world. This allowed the researchers to see inside yeast cells and freeze the break-induced DNA repair process at different times. They found that this mode of DNA repair doesn’t rely on the traditional replication fork — a Y-shaped region of a replicating DNA molecule — but instead uses a bubble-like structure to synthesize long stretches of missing DNA. This bubble structure copies DNA in a manner not seen before in eukaryotic cells.

Traditional DNA synthesis, performed during the S-phase of the cell cycle, is done in semi-conservative manner as shown by Matthew Meselson and Franklin Stahl in 1958 shortly after the discovery of the DNA structure. They found that two new double helices of DNA are produced from a single DNA double helix, with each new double helix containing one original strand of DNA and one new strand.

“We demonstrated that break-induced replication differs from S-phase DNA replication as it is carried out by a migrating bubble instead of a normal replication fork and leads to conservative DNA synthesis promoting highly increased mutagenesis,” Malkova said.

This desperation replication triggers “bursts of genetic instability” and could be a contributing factor in tumor formation.

“From the point of view of the cell, the whole idea is to survive, and this is a way for them to survive a potentially lethal event, but it comes at a cost,” Lobachev said. “Potentially, it’s a textbook discovery.”

During break-induced replication, one broken end of DNA is paired with an identical DNA sequence on its partner chromosome. Replication that proceeds in an unusual bubble-like mode then copies hundreds of kilobases of DNA from the donor DNA through the telomere at the ends of chromosomes.

“Surprisingly, this is a way of synthesizing DNA in a very robust manner,” Saini said. “The synthesis can take place and cover the whole arm of the chromosome, so it’s not just some short patches of synthesis.”

The bubble-like mode of DNA replication can operate in non-dividing cells, which is the state of most of the body’s cells, making this kind of replication a potential route for cancer formation.

“Importantly, the break-induced replication bubble has a long tail of single-stranded DNA, which promotes mutations,” Ramakrishnan said.

The single-stranded tail might be responsible for the high mutation-rate because it can accumulate mutations by escaping the other repair mechanisms that quickly detect and correct errors in DNA synthesis.

“When it comes to cancer, other diseases and even evolution, what seems to be happening are bursts of instability, and the mechanisms promoting such bursts were unclear,” Malkova said.

The molecular mechanism of break-induced replication unraveled by the new study provides one explanation for the generation of mutations.

This research is supported by the National Institutes of Health under awards RO1GM082950, RO1GM084242, RO3ES016434, GM76020, and by the National Science Foundation under award MCB-0818122. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the NIH or NSF.

CITATION: N. Saini, et al., “Migrating bubble during break-induced replication drives conservative DNA synthesis,” (Nature, 2013). http://dx.doi.org/10.1038/nature12584

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The National Science Foundation has awarded a 5 year grant of approximately $2.0 million to fund a collaborative group of scientists: Mark Young (PI, Montana State), Joshua Weitz (Co-PI, Georgia Tech), and Rachel Whitaker (Co-PI, UIUC) to study the role of viruses in shaping genetic, taxonomic and functional diversity.

The team will investigate a new hypothesis about how viruses may control the structure and function of microbial communities. The traditional view of viruses is that they negatively impact the fitness of infected hosts. In other words, they are viewed strictly as pathogens, in which the host tries to eliminate the virus. This project will explore an alternative hypothesis: that chronic viral infections contribute positively to host fitness, increasing the success of the virus-host pair by protecting their hosts from infection by even more pathogenic viruses.