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.

Two proposals by Georgia Tech researchers, Dr. Frank Stewart (Assistant Professor, School of Biology) and Dr. Kostas Konstantinidis (Carlton S. Wilder Assistant Professor, Civil and Environmental Engineering; joint appointment in Biology; http://enve-omics.gatech.edu), have been selected for the Department of Energy's 2014 Community Science Program.  The CSP provides high-throughput DNA sequencing resources to support genomics research of relevance to urgent energy and environmental challenges. Dr. Stewart's project seeks to understand how oxygen loss, such as that caused by agricultural runoff, affects microbial pathways of carbon and energy flow in marine ecosystems.  Dr. Konstantinidis' project will explore how microbes survive in the extreme environment of the upper troposphere.   This project represents a "bold new direction" for the DOE CSP program and may contribute insight into how microbes affect cloud formation and the Earth's water cycle.  Additional details about 2014 CSP projects can be found at http://www.jgi.doe.gov/News/news_13_10_28.html

Funding for research is a highly competitive endeavor under the best of circumstances. For Georgia Tech doctoral student Troy Alexander, a new avenue for funding has opened.

Alexander works as a researcher in School of Biology Professor Julia Kubanek’s group. His latest project seeks to accelerate the discovery of new medicines for the treatment of cancer and infectious diseases by studying Fijian red algae.

To help raise funds to support this research, Alexander and Kubanek posted the project on Georgia Tech Starter, a university-based, peer-reviewed crowdfunding platform for faculty-sponsored scientific research projects.

Alexander established a fundraising goal of $9,450 to fast-track the discovery of these new medicines through a combination of biomedical screening, nuclear magnetic resonance spectroscopy, and multivariate statistical analysis of his library of marine chemical compounds from the Fijian organisms. By identifying unknown molecules, the research will prioritize exploration of previously unseen structures that can exhibit strong potency toward microbial and human cancer cell lines.

“These molecules previously unknown to science will be carried forward for purification, structure determination, and development as treatments for disease,” Alexander said.

Georgia Tech Starter is a perfect venue for making human medicine research advances more accessible to a general audience, he added.

According to Allison Mercer, an applied physicist at Georgia Tech Research Institute – and the mastermind behind Georgia Tech Starter – using crowdfunding for science means there is a community of people invested in the research, witnessing its benefits and outcomes.

“There is incredible potential for contributors to engage with scientists in a way that hasn’t been done before: A project that is successfully funded converts into a blog through which only project supporters can monitor the progress of the project, ask the scientists questions, and witness world-class research at Tech as it unfolds.”

But, before taking a step to gain the world’s attention through Tech Starter, researchers need to consider several things, Alexander said: One is the amount of funding to request.

“The amount we seek to raise should be large enough to make an impact on our research, but it shouldn’t be so large to sound insurmountable to potential donors,” he said.

“Another item to consider is how easily one can make their research appeal to a broader audience,” he said. “Do you have any tangible goals that can be achieved within the first year as proof of progress to donors? Are you willing to commit to engaging with the audience – from making the video to maintaining social media contact? These are huge commitments, and they need to be managed without becoming a drain on research time.”

Lastly, Alexander advises that the goals of the project need to be easy to explain and justify. Short-term goals should be clear to give investors something to anticipate. And, he said, researchers should be prepared for the contingency that the funds might not be raised.

Like other crowdfunding platforms, Georgia Tech Starter operates with an all-or-nothing funding strategy. Only if the project goal amount is reached within a 60-day window, are donors’ credit cards charged. This helps assure supporters that the researchers will only receive the pledged money if they have enough total funds to achieve the stated project goals. Some research efforts are scalable, but many are not.

“If it costs a million dollars to launch a telescope into space, it doesn’t do you any good to get halfway there,” said Mercer.

Students interested in taking advantage of Tech’s crowdfunding site can visit starter.gatech.edu to submit their contact information.

The process for getting a project posted on Georgia Tech Starter includes a comprehensive peer review of the project to ensure that: it is achievable; the requested funding amount is enough to complete the project; and the researchers on the project have the knowledge, skills, and abilities to get the research done right. Through the peer review process, researchers will receive feedback on how to better craft the project’s message for posting.

“We do everything we can to support the project creators so they can be successful,” said Mercer.

Danielle Dixson is a new faculty member in the School of Biology this year, but she’s not new to Georgia Tech. She spent the previous two years as a post-doctoral fellow in Professor Mark Hay’s lab. Before that she received her Ph.D. from James Cook University in Australia and her B.S. from the University of Tampa. One might say she was brought up with biology in her future … the Minnesota Zoo was right behind her back fence as a kid.

Danielle Dixson: The Minnesota zoo has a special kind of school, kind of like a flagship school, it’s called the School of Environmental Studies. It’s actually at the zoo. So you take all your classes your junior and senior year at the zoo, and they incorporate biology into everything that you’re doing. So I got to take marine biology in Minnesota as a junior, because we got to use the aquariums there.
 
David Terraso: So, is that where your interest in biology began?

Dixson: I’m one of those kids who, when I was five, I said I wanted to be a marine biologist and my parents were like ok. And to anyone who asked, I said, “Oh, I want to be a marine biologist.” They said, “Oh, ok,” thinking I would grow out of it or something. It’s like every little kids dream, but I never changed my mind.

Terraso: Tell us about your research and what you’re looking to do in the next few years.

Dixson: My research in general is how do chemical cues, or smells in the water, give information that cause a behavioral response in fish.  So, what smells elicit certain behavioral patterns, and how does that reflect in community dynamics and settlement selection.
A lot of my work looks at larval fish, or juvenile fishes. And when marine fish reproduce they lay eggs, or spawn into the water column, and the larva, or the eggs, go off into the pelagic environment, and they need to come back to the reef. And what I’m trying to figure out is what chemical cues do they use to decide what reef is a good reef and what reef is a bad reef.

Terraso: Tell us about some of your research projects.

Dixson: So a big project of mine in Fiji is looking at the marine protected areas there, looking at how, if you have a protected area there that’s a very pristine, healthy habitat and you have one that’s a very non-pristine protected area (where it’s essentially trashed because people fish in it and are always in it and there’s runoff and a lot of algae and not a lot of fish) looking at how we can get coral back into that non-protected area. And it seems like the chemical cues may be responsible for the coral and fish larva rejecting that area as a habitat, because it’s so different from the healthy area right next door. So that’s been one of the primary focuses of my post-doc, and I’ll continue doing some of that work with Mark Hay as well.

Another thing that I work on is ocean acidification and the effect that that has on behavior and the effect that that has on mostly larval fishes. I’ve started doing some projects on sharks that I’ll continue while at Tech. I’ve been talking to the Georgia Aquarium about collaborating with them and using some of their shark eggs that they get pretty regularly and treating them with different levels of ocean acidification scenarios that are going to be happening in the near future, within the next 100 years, and looking at how that’s affecting the behavioral response of the animals.

Terraso: Looking further into your career, say 30 years from now, what do you want to have accomplished?

Dixson: I guess 30 years out, I’d like to continue in the same role and be able to have provided the marine community with a much better understanding of how chemical cues work in the marine environment and how the sensory system plays a huge roll in the behavior that comes across with fish and coral larvae.

In the recent past, we’ve been thinking these tiny fish larvae, when they were out in the open ocean, that they were just passive particles drifting around with no say in where they were going. And now in a very short time, it’s been shown, mostly through the ability to use genetics in different ways, that they’re actually going to specific places. We don’t know why they’re going to those specific places. We don’t know how they’re able to manage to get to these places, but clearly their behavior is not passive.

They’re overcoming ocean currents. They’re overcoming all of these obstacles that we thought they would not be able to do. And they’re getting to these locations and their behavior is really the only way you can explain it.

In order to do something, you need a motive to do it, and the sensory cues are what provides them information to decide where to go. So I’d really like to get into how different sensory systems interact. So if you get an auditory cue and an olfactory cue and the olfactory cue is a positive stimulus, but the auditory cue might not sound right, which would you follow? What choices will you make?

Georgia Tech faculty continue to be recognized as among the most respected in their field. Last month, the American Association for the Advancement of Science (AAAS) named four — in biology, computing and engineering — to its 2013 class of fellows

Election as a fellow of AAAS, the world’s largest general scientific society, is an honor bestowed upon members by their peers. Fellows are recognized for meritorious efforts to advance science or its applications.

New fellows include:

• School of Interactive Computing Professor Henrik Christensen, cited “for contributions to applied estimation methods in mapping, robot localization, visual tracking and recognition, as well as national-level leadership of the robotics community.”
• School of Biology Professor Mark Hay, cited “for distinguished contributions in ecology, particularly for developing marine chemical ecology and for elucidating how chemical cues and signals structure populations, communities, and ecosystems.”
• School of Chemical and Biomolecular Engineering Professor Hang Lu, cited “for distinguished contributions to the field of engineering systems for high-throughput quantitative and systems biology, particularly for microfluidics, automation, image-based science, and phenomics.”
• School of Aerospace Engineering Professor Suresh Menon, cited “for distinguished and innovative contributions to the field of multi-scale computational simulation and modeling of turbulent combustion in power and propulsion systems.”