The National Institute of Environmental Health Sciences has awarded Dr. Francesca Storici, Associate Professor in the School of Biological Sciences, a new five-year grant entitled “Ribose-seq profile and analysis of ribonucleotides in DNA of oxidatively-stressed and cancer cells”. This $1.4 million project will focus on ribonucleoside monophosphates (rNMPs), the subunits of RNA, that are the most common non-canonical nucleotides found in genomic DNA with several thousands in the yeast genome and more than a million in mouse DNA. These rNMPs distort the DNA double helix, altering DNA function and increasing DNA fragility and instability. There is a pressing need to determine where rNMP sites are in DNA, especially in cells that are under stress and/or with abnormal genome stability, like cancer cells. Storici’s team developed a method to map rNMPs in genomic DNA ‘ribose-seq’ and applied it to the yeast cells. They discovered a widespread, but not random distribution of rNMPs with several hotspots in nuclear and mitochondrial DNA. This new project, together with collaborators Dr. Fred Vannberg from the School of Biological Sciences and Dr. Gianluca Tell from the University of Udine in Italy, will investigate how the profile of rNMP incorporation into genomic DNA changes upon oxidative stress, and whether there is any link with cancer phenotypes.
Timothy C. Cope, a professor in the School of Biological Sciences and the Wallace H. Coulter Department of Biomedical Engineering and a member of the Parker H. Petit Institute for Bioengineering and Bioscience, has been appointed to the Clinical Neuroplasticity and Neurotransmitters (CNNT) Study Section at the Center for Scientific Review, a branch of the National Institutes of Health (NIH).
According to NIH, the CNNT Study Section “reviews applications describing small animal and subhuman primate models of epilepsy, neurodegeneration (Parkinson’s disease, Amyotrophic Lateral Sclerosis, diabetic neuropathies) and spinal cord injury.”
"I see study section service as an important responsibility,” Cope says. “It's also a valuable opportunity to learn how fields are trending and to stay up with conceptual and technical advances.”
Cope will serve on the study section until June 30, 2020. During his tenure, he will review grant applications submitted to the NIH, make recommendations on these applications to the appropriate NIH national advisory council or board, and survey the status of research in the field.
“These functions are of great value to medical and allied research in this country,” says Richard Nakamura, the director of the Center for Scientific Review. “Membership on a study section represents a major commitment of professional time and energy, as well as a unique opportunity to contribute to the national biomedical research effort.”
“We’re proud every time one of our faculty members is chosen for study section service,” says J. Todd Streelman, chair of the School of Biological Sciences. “For Tim in particular, it means that he is well-respected by his peers and by the NIH. Study section service is hard work, but it’s rewarding to be part of the process.”
Streelman himself serves on the Skeletal Biology Development and Disease (SBDD) Study Section. Other School of Biological Sciences faculty members who serve on NIH study sections are Hang Lu, Enabling Bioanalytical and Imaging Technologies (EBIT) Study Section; Eric A. Gaucher, Genetic Variation and Evolution (GVE) Study Section; Lewis A. Wheaton, Risk, Prevention and Health Behavior (RPHB) Integrated Review Group; and M.G. Finn, Nanotechnology (NANO) Study Section.
College of Sciences
Dr. Francesca Storici, associate professor in the School of Biological Sciences, was awarded $690,000 for a 3 year project to study the mechanisms of RNA-DNA recombination. This project is funded by the National Science Foundation’s Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences. Dr. Storici and collaborators recently discovered a novel mechanism of genetic recombination and DNA damage repair via exchange of genetic information from RNA to DNA in budding yeast cells, yet little is known about how this process is activated and regulated. The proposed research will enable mechanistic characterization of this newly discovered phenomenon and describe how RNA participates in DNA repair. The study also will provide important biological insights to better understanding the physiological role of RNA in DNA stability and its impact on genome maintenance and evolution. The work is significant because it will provide molecular understanding how cells repair their DNA and how this process goes wrong in diseases like cancer. The expected discoveries will be integrated into classroom topics and activities for many graduate and undergraduate students. Through the inclusion of a Research Experience for Teachers (RET), the project will engage numerous students from a local, 100%-minority high school in lab experiences, and will support student participation in Science, Technology, Engineering and Math (STEM) programs, particularly in molecular biology.
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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Writer and contact: Ben Brumfield
Popular Science has named William C. Ratcliff, an assistant professor in the School of Biological Sciences, one of its Brilliant 10 for 2016. The list is how the magazine “honors the brightest young minds reshaping science, engineering, and the world.”
Ratcliff is an evolutionary biologist. He studies how multicellular clusters form from single cells and how the clusters become sophisticated through evolution. His work has been featured in Quanta Magazine, Scientific American, New Scientist, and other science magazines. For a fun explanation of his work, which Ratcliff gave at the 2015 Atlanta Science Festival, watch this video.
In the following Q&A, Ratcliff talks about his work, early love for biology, and more.
What is your research about?
Evolutionary biologists study how organisms change over time. My niche is understanding the origin of complex life, specifically how multicellular organisms can evolve from single cells.
Multicellularity evolved on Earth many times for different groups, from slime molds to animals. This evolutionary step occurred long ago and has been hard to study, largely because biologists haven’t had good ‘hands on’ model systems of early multicellular organisms and their actual unicellular ancestors.
In our lab, we do evolutionary time travel in a test tube, by creating new multicellular organisms, using yeast and algae, in a way that’s simple but which we can examine with huge precision, using all the tools of biology, as well as mathematics.
We’re not trying to explain what happened historically. Rather, we’re trying to show how it can happen in principle. We want to understand how single-cell organisms evolve to form groups and how those groups evolve to become more complex. We’re interested in how the geometry of cellular clusters influences the outcome of evolution, tipping the balance between cellular cooperation and conflict, and how cells lose their Darwinian autonomy, evolving from individual organisms into parts of a new organism. These are fundamental principles that should be broadly applicable.
What has been the most exciting time in your research life so far?
Setting up a new lab in Georgia Tech is unquestionably the most exciting so far. When you start a new lab, you have this war chest of startup money. You can buy the lab equipment you could just dream of before. You have resources to blow the lid off the constraints you previously had. You can hire people to do cool stuff. It’s like winning a lottery.
I would have had fun starting a lab anywhere, but unique to Tech is the collaborative opportunities I’ve had here. About a year after I started, I met Peter Yunker, a physicist who works with colloidal particles and soft matter. He had ideas for studying multicellularity through a physical lens that absolutely blew my mind. We now have students working together on projects, and my research has taken a totally new path.
Also, Sam Brown was hired shortly after I arrived. Sam is a mathematical microbiologist. Working with Sam has opened lots of doors into integrating modeling more explicitly in our work.
Over lunch a year and a half ago, Brian Hammer and I decided to do a project together, and now we have a paper in review examining the ecological and evolutionary consequences of ‘hand-to-hand’ combat – obviously bacteria don’t have hands, but it’s similar – in bacteria.
Did you have early life experiences that paved the way for you to be where you are now?
I’ve always thought of myself as a science geek and a biology nerd. My earliest memories are of playing with ladybugs swarming up a tree when I was two years old. I did a science fair project with yeast when I was six years old. I’m still working with yeast cells now.
I’ve always been interested in the lives of living things. My parents played a huge role in fostering that interest. My brother and I grew up in Berkeley, Calif. I had a vegetable garden in the backyard, and my dad built me a greenhouse where I grew orchids.
We also have family property on the coast near Mendocino, which my great-grandfather bought almost 100 years ago. As kids, we spent months at a time there, running around the woods, like Huck Finn and Tom Sawyer poking around the beach and hiking way up through the forest for hours at a time. We occupied ourselves by poking our noses into the workings of living organisms. We wondered how all these things were changing from day to day. How did they deal with changing weather? What were they eating? As my dad says, “Boredom is the crucible of creativity”, but I don’t really remember being bored.
If you couldn’t be a scientist, what would you have done professionally?
I had become an avid stock trader toward the end of high school. As a college freshman I had to choose between economics and biology. I decided to stick with biology, thinking it would be more fun. That was a good call.
I’d also enjoy computer programing or big-data analytics. When I learned coding, it was almost like a drug. You can do so much, so fast, and writing code is like playing a 3D crossword puzzle. Had I learned it earlier, I wouldn’t have been a bench scientist.
When you were thinking where to settle after your postdoc, why did you choose Tech?
Partly, because Atlanta was a place my wife would move to.
What really drew me to Tech was the abundance of supersmart, nerdy people. The average Tech undergrad knows how to code. Many of them want to become doctors, but they also know calculus and (the programming language) Python.
I wanted to surround myself with bright people who are quantitative. Plus, it’s nice that the College of Sciences is so interdisciplinary, that our school values collaboration, and that campus is small enough that you run into people from far-flung disciplines.
In your encounters with students at Tech, what has surprised you about them?
They are so good! Their desire and ability to work hard, their interest in the material is way up – 75% of my students are as good as the top 10-15% of those I’ve taught previously.
What about your job do you like the least?
It’s the sheer number of different things we have to do as professors. Our time is split into so many little bins. I miss having that open space to think broadly and deeply about science.
What’s something about yourself that’s not obvious to your colleagues?
Everyone assumes that I’m laid back because I’m an outgoing person and pretty happy, but I’m usually running around at a half jog and trying to get a million things done.
I like to play music – guitar and ukulele – to relax. I picked up the ukelele when my daughter was born because it’s smaller and quieter, and you can play it with a baby on your lap. I play a lot of bluegrass. I also garden and raise chickens; we harvest five eggs a day on average.
What bit of wisdom would you like to share to incoming freshmen?
I would tell them to study the things that they think are fun and cool and don’t be afraid to get their quantitative game on. Don’t shirk the math and programming because it’s going to be so valuable later.
Definitely take classes because you think they’ll be cool because ultimately it’s your own interests that motivate and drive you.
Also, find a lab early on if you’re interested in research. One of the main benefits of being at Tech is the opportunity to do primary research and interface with faculty, postdocs, and grad students. But this amazing opportunity comes only if you seek it. Find a lab you like in your first few years, and if you like it, by the end of school you’ll have a deep well of experience that you wouldn’t otherwise have, and you will have way more opportunities as a result. Nobody writes a better letter of recommendation than a professor who has known you for years!
What places do you want to visit that you haven’t visited yet?
Vietnam, because my wife’s family is out there and I haven’t been there yet. Cambodia would be really cool to see. I’d love to see an active volcano, any one of them! South Africa is another choice because it is a refuge for African plant diversity.
I’m also an amateur photographer, and after getting more into night photography, I would love to visit somewhere where I could take great photos of the Milky Way without light pollution, like the Mojave Desert.
With whom from history would you like to join for dinner?
I know this is cliché, but I would love to meet Charles Darwin. He laid out so much of the field 150 years ago, and it would be fun to just blow his mind. I’d love to update him about how the field has developed, how generally well-supported his ideas are, and how cool the nitty-gritty mechanistic details of evolution are. Dinner might stretch on a bit late, though.
Joshua S. Weitz, professor in the School of Biological Sciences, has written a postgraduate textbook which has been selected for the shortlist of the Royal Society of Biology's annual book awards.
A new study in the journal Nature analyzes genomic diversity in 125 human populations at an unprecedented level of detail, tackling questions related to our species’ demographic history and dispersal out-of-Africa. The study is based on 379 high-resolution whole-genome sequences from across the world, generated by an international collaboration led by Mait Metspalu from the Estonian Biocentre, Estonia, and Toomas Kivisild from the University of Cambridge, U.K.
“This endeavor was uniquely made possible by the anonymous sample donors and the collaboration effort of nearly 100 researchers from 74 different research groups from all over the World,” Metspalu said.
The lab of Joseph Lachance in the School of Biological Sciences at Georgia Institute of Technology is one of these research groups. “By studying a global panel of individuals, we are able to identify genetic variants that are shared among different subsets of humanity and decipher our evolutionary past,” Lachance said.
The high geographic coverage of the samples permitted the researchers to study many aspects of genetic and phenotypic differences between individuals and populations using a common spatial framework. Researchers found that the sharpest genetic gradient in Eurasia separates East and West Eurasians. This barrier runs roughly along the Ural Mountains in the north, opens in the Steppe belt connecting Central Asia to South Siberia, and becomes strong again on the Tibetan plateau, elongating south toward the Indian Ocean while separating South and Southeast Asia.
In addition to increasing our understanding of the challenges that humans faced when settling down in ever-changing environments, the deluge of freely available data will serve as future starting point to further studies on the genetic history of modern and ancient human populations.
Francesca Storici, associate professor in the School of Biological Sciences and a researcher in the Petit Institute for Bioengineering and Bioscience, has been named a Howard Hughes Medical Institute (HHMI) Faculty Scholar.
Storici is one of 84 scientists from 43 institutions across the U.S., in first cohort of researchers who are receiving this first-time award supported by HHMI, the Simons Foundation, and the Bill & Melinda Gates Foundation.
“This is an awesome grant, really, because the goal is to support creative researchers. It’s not about a specific project with specific aims,” says Storici. “The award has been possible thanks to the exceptional dedication and enthusiasm of all my group members at Georgia Tech.”
Storici’s lab will receive $1.5 million over five years. The awards target early career scientists who have great potential to make unique contributions to their field, according to HHMI, who joined forces with the Simons and Gates foundations to create the program in response to growing concern about the significant challenges that early-career scientists face.
The career trajectory for these researchers has become much less certain as competition for grant support intensifies. In the last two decades, the U.S. has witnessed a sharp decline in the success rate for National Institutes of Health (NIH) research awards, as well as a striking increase in the average age at which an investigator receives his or her first R01-equivalent grant.
“Support for outstanding early-career scientists is essential for continued progress in science in future years,” notes Marian Carlson, the Simons Foundation’s director of life sciences.
HHMI was concerned that the time-consuming (and often frustrating) quest for grant funding could sap the creativity and energy that researchers bring to starting their own labs. Within a few years of a new faculty appointment, a researcher's institutional start-up funds typically come to an end. Pressure to secure federal grant money may lead to “safe” grant proposals. As a result, creative and potentially transformative research projects may fall by the wayside.
“This program will provide these scientists with much needed flexible resources so they can follow their best research ideas,” says HHMI Vice President and Chief Scientific Officer David Clapham.
The Storici lab’s research focuses on ribonucleotides embedded in DNA; RNA-driven DNA repair and modification; mechanisms of genomic stability/instability; and gene targeting and genome editing.
The Storici lab’s research focuses on RNA-driven DNA repair and modification; function and consequences of ribonucleotides embedded in DNA; mechanisms of genomic stability/instability; and gene targeting and genome editing.
Storici is considered a pioneer in the emerging field of RNA-mediated genome stability and instability. Her research led to the discovery of transcript RNA-templated DNA repair and recombination. The Storici group also has developed new tools to better understand the genetic and epigenetic consequences of the presence of RNA in DNA.
The HHMI award is just the latest in a string of recent successes for Storici. In August came two major announcements: a three-year grant from the National Science Foundation to gain new insight into the impact or RNA on genome maintenance, and a five-year, $1.4 million grant from the NIH supporting a collaborative effort with the lab of fellow Petit Institute researcher Fred Vannberg (assistant professor in the School of Biological Sciences) as well as the University of Udine in Italy.
Early-career researchers (four to 10 years of faculty experience) were eligible to apply for this competition. Distinguished scientists reviewed and evaluated more than 1,400 applicants on their potential for significant research productivity and originality, as judged by their doctoral and postdoctoral work, results from their independent research program, and their future research plans.
Expenses covered by the grant will include partial salary for faculty, salary for lab personnel, equipment, supplies, travel and publications.
Emeritus Professor Gerald (Jerry) Pullman was awarded a lifetime achievement award for outstanding contributions in somatic embryogenesis and other vegetative propagation technologies by the Fourth International Conference of the International Union of Forest Research Organizations focused on Somatic Embryogenesis and Other Vegetative Propagation Technologies held in September 2016 in Buenos Aires, Argentina.
Dr. Gerald Pullman, Emeritus Professor in the School of Biology, was recognized for his outstanding contributions and scientific endeavors in the vegetative propagation of trees, especially somatic embryogenesis in conifer species. The lifetime achievement award was presented at the Fourth International Conference of the International Union of Forest Research Organizations (IUFRO Unit 2.09.02) held September 19-23 in La Plata, Buenos Aires, Argentina. The conference participants gathered to discuss “Development and application of vegetative propagation technologies in plantation forestry to cope with a changing climate and environment”. The membership of the unit currently includes 742 scientists from 341 affiliations and 65 countries.
As demands for forest products grow and the land base to produce trees shrinks, it will become necessary to produce trees that produce more wood and fiber per acre, with improved wood and fiber properties. Clonal propagation of trees with desired growth and processing characteristics will facilitate this goal.
Jerry’s research interests for the past 35 years have been in the areas of multiplication of high-value trees through somatic embryogenesis, understanding the fundamental physical and chemical factors driving natural plant embryo development, creation of tissue culture systems necessary for the genetic engineering of forest trees and methods to propagate and conserve rare and endangered Southeastern plants. Jerry has over 120 publications with 55 focused in the field of somatic embryogenesis and additional publications on understanding seed conditions occurring during natural embryo development, vegetative propagation of forest trees, and conservation of endangered species through tissue culture and cryogenic storage.
Jerry continues to lead a small tissue culture program at the Georgia Tech Renewable Bioproducts Institute focused on conifer somatic embryogenesis and conservation of rare and endangered species in the Southeast. The research on rare and endangered plants is in partnership with the Atlanta Botanical Garden and often works with School of Biology undergraduate students.
Editor's Note: This item was originally published as a blog post in the Amplifier.
A recent study published in the Proceedings of the National Academy of Sciences analyzed the viral content of the human gut (Manrique et al., PNAS, 2016). The research focused on a particular kind of virus called bacteriophage, which only infect bacterial cells and do not infect human cells. Manrique and colleagues found that healthy individuals had a “core” group of bacteriophage. In addition, they found that these core bacteriophage were less frequently found in individuals with gastrointestinal disease. This novel finding reveals a potential link between the viruses in our gut and our health.
Joshua Weitz, a professor in the School of Biological Sciences explains the findings:
Yogurt is a breakfast staple. In my family, we pack single-serve yogurt containers with our kids’ lunches and eat “stinky” cheese. In doing so we are also serving our children bacteria. Intentionally. Yogurt and cheese are examples of “living” food. The living component are cultures of bacteria.
As any shopper knows, the marketing of yogurt is tied not just to its taste but to its health benefits. The active bacteria in yogurt differ among company and brands. Irrespective of the brand-name, the active bacteria are nearly all close relatives of “lactic acid bacteria”. Lactic acid bacteria take the sugars in milk, break them down, and release lactic acid. That lactic acid and other byproducts give yogurt its distinctly sour taste.
The idea that eating more bacteria could be good for you reflects a paradigm shift in the scientific attitude towards microbes and health. Bacteria can make us sick. But, many bacteria keep us healthy. We could not go about our daily routine without them. These bacteria constitute part of our “microbiome” – that is the world of bacteria that lives in and on us. Yet, despite the changing attitudes towards bacteria, there has not been a similar paradigm shift with respect to viruses. I have yet to see a yogurt offered with extra viruses. I would imagine it would not be a sales hit… Or would it?
The study of Manrique and colleagues identified a core “virome” correlated to human health. But we still do not know if there is a causative link between the two, e.g., do bacteriophage in the human virome infect components of the healthy human microbiome and/or do they infect otherwise harmful pathogens? Future research will be needed to tease apart these relationships. But one thing is clear: consumers may eventually need to consider the health benefits of viruses and bacteria when thinking about maintaining or improving their health.
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