Will Ratcliff is having a moment in the spotlight for getting yeast and algae to jump through hoops to new evolutionary heights.
The magazine Popular Science has heaved the researcher from the Georgia Institute of Technology into its annual list “The Brilliant 10,” a select roster of “the 10 most innovative young minds in science and technology.” Ratcliff was praised for advancing the study of cellular evolution.
PopSci cited his work demonstrating how single-cell organisms may have transitioned into simple multicellular organisms ages ago. It’s widely seen as an arduous evolutionary leap, since single cells had to forfeit a lot of their own fitness for the greater good of creating viable cell groups.
“William Ratcliff revealed surprising insights into what might have been necessary for this transition to occur,” Popular Science wrote in its September/October edition. He has illuminated “one of the greatest mysteries of life.”
The needs of the many
Ratcliff, an assistant professor in Georgia Tech's School of Biological Sciences, has put thousands of generations of yeast and many generations of algae cells through stresses in the lab devised to get them to evolve better survival strategies around forming cohesive groups.
“We’re figuring out kind of clever ways to get them to form groups and then for those groups to become more complex,” he said.
The idea is to end up with a rudimentary multicellular being with cells taking on specialized roles, a very early step on the pathway to organ development. But the first advantage to group formation is simple -- size. Bigger is often better.
“A lot of small predators have small mouths that are great at eating single-cells,” Ratcliff said. But big multicellular cell clusters are too big for these predators to get their mouths around. Clustered cells survive to pass on their genes.
Race to the bottom
To accelerate the evolution of yeast from individuals cells into cell groups called “snowflakes,” one of his signature achievements, Ratcliff has selected for yeast cells that sink more quickly. There, again, big clusters sink better than single cells.
Once clusters are done outcompeting the unicells, they compete against each other. “It’s remarkable how quickly snowflake yeast clusters evolve new traits that let them win this race,” he said.
While the group gains various strengths, it sacrifices the viability of individual cells. “They evolve a division of labor in the group, in which some of them commit suicide,” Ratcliff said. That changes reproductive patterns, which makes the clusters’ progeny more competitive.
The loss of individual cell fitness is extensive.
The more robust a cluster gets, the less likely its individuals are to survive if they are caused to revert back to individual cells. It’s like an odd twist on the traditional marriage vows: Part, and you will die.
Much of Ratcliff’s research is funded by NASA’s Exobiology program and the National Science Foundation.
Felt it coming
Before Popular Science called for an interview for its four-paragraph nod, Ratcliff had sensed something was coming. For a few months, while the magazine cemented its list, it asked around at scientific societies about noteworthy up-and-coming researchers.
As a result, Ratcliff received some veiled tips.
“A couple of colleagues of mine said, ‘Hey man, I got a call from a reporter. I can’t tell you anything about it, but you may be hearing something soon,’” he said.
When PopSci called, a reporter told Ratcliff that many scientists had mentioned him, strongly influencing the decision to name him one of "The Brilliant 10." “That was very touching that people within the research community said to them they should look at my lab,” Ratcliff said.
Hail Mary pass
Life’s small coincidences have helped guide Ratcliff’s academic strivings down the path of evolutionary research.
His career in biology spawned from childhood, when his parents carted him and his brother Felix off in their summers to woodland family cabins next to craggy Pacific Coast cliffs near Mendocino, California. “There was really nothing to do except to run around the forest and the ocean checking out the lives of plants and animals,” Ratcliff said.
They got hooked; both brothers became biologists.
Plants became Ratcliff’s passion at an early age, which led to a bachelor of science in plant biology from the University of California, Davis, but that threw his career a serendipitous curve. “I thought it would have a lot to do with ecology, but it turned out to be mostly cellular biology.”
The decision to see if yeast cells could be coaxed into making the leap to multicellularity was also slightly capricious. “There was a lot of doubt surrounding it, but I thought, ‘Why not just give it a try and see,’" said Ratcliff, whose Ph.D. is in ecology.
He was astonished when that longshot worked. “It was a kind of Hail Mary pass,” he said. It led to a dedicated research specialization and a notable body of continuing work.
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Using cryo-electron tomography, Georgia Tech and Emory University researchers have captured images of measles viruses as they emerge from infected cells. The work advances the understanding of measles and related viruses and could suggest antiviral drug strategies likely to work across multiple members of the family that includes measles virus.
The results were published in Nature Communications.
Scientists led by Elizabeth Wright and Zunlong Ke say they can discern an internal matrix protein acting as a scaffold, with the encapsidated genetic material visible as “snakes” close to the viral membrane.
An effective vaccine is available against measles virus, which is a highly infectious pathogen. Yet scientists still don’t understand a lot about it, Ke says. Understanding the internal organization of measles virus could guide the study of related viruses, such as parainfluenza and respiratory syncytial virus (RSV), which are common causes of respiratory illnesses, as well as Nipah virus, an inspiration for the film “Contagion.”
Wright is an associate professor of pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta, director of the Robert P. Apkarian Integrated Electron Microscopy Core, and a Georgia Research Alliance Distinguished Investigator. She has an adjunct appointment in the Georgia Tech School of Biological Sciences.
Ke is a former Georgia Tech Ph.D. student of Wright’s. Ke is starting a postdoctoral position this summer at the MRC Laboratory of Molecular Biology in Cambridge, U.K.
After working with purified viruses for a long time, Wright, Ke, and colleagues decided to examine virus-infected cells. The team collaborated with Richard Plemper, who specializes in measles virus and is now at Georgia State University.
The family of viruses that includes measles, called paramyxoviruses, is difficult to handle because of their low titers, instability, and heterogeneity, Wright says. For structural studies, researchers usually concentrate and purify viruses by centrifuging them through thick solutions. But this method is tricky for measles virus, which are squishy and prone to bursting. For this reason, they are difficult to visualize.
“Instead, we grow and infect the cells directly on the grids we use for microscopy and rapidly freeze them, right at the stage when they are forming new viruses,” Ke says.
Improvements in technology have increased the resolution of imaging. Cryo-electron tomography, which is ideal for viruses that come in different shapes and sizes, uses an electron microscope to obtain a series of 2D pictures of the viruses as the sample holder is tilted to multiple angles along one axis. The images and the angular information are then used to compute the 3D volume of the virus, much like a medical CT scan, Wright says.
“We would never see this level of detail with purified virus, because the process of purification disrupts and damages the delicate virus particles,” she says. “With the whole-cell tomography approach, we can collect data on hundreds of viruses during stages of assembly and when released. This allows us to capture the full spectrum of structures along the virus assembly pathway.”
For example, the scientists can now see the organization of glycoproteins on the surface of the viral membrane. Previous work showed two glycoproteins were present on the membrane, but they were a “forest of trees,” with insufficient detail to identify each one.
In this study, the team resolved the two glycoproteins and determined that one of them, the fusion (F) protein, is organized into a well-defined lattice supported by interactions with the matrix protein. In addition, they could see “paracrystalline arrays” of the matrix protein, called M, under the membrane. The arrays had not been seen in measles virus-infected cells or individual measles virus particles before, Wright says. Under the microscope, these arrays look like Lego grid plates, from which the rest of the virus is built and ordered.
The new 3D structures also argue against a previous model of viral assembly, with ribonucleoprotein genetic material as a core and the M protein forming a coat around it.
The scientists are still figuring out what makes measles virus take a bulbous shape while RSV is more filamentous. Ke thinks the scaffold role of M is similar for related viruses; however, as the virus assembles, individual structural proteins may coordinate uniquely to produce virus particles with different shapes that better support their replication cycle.
This work was supported in part by Emory University; Children’s Healthcare of Atlanta; the Georgia Research Alliance; the Center for AIDS Research at Emory University (P30 AI050409); the James B. Pendleton Charitable Trust; public health service grants R01AI083402 and R01HD079327, R01GM114561, R21AI101775, and F32GM112517; and NSF grant 0923395.
EDITOR’S NOTE: This article is an abridged and slightly modified version of the original story by Quinn Eastman published in the Emory News Center on April 30, 2018.
For much of its first two billion years, Earth was a very different place: oxygen was scarce, microbial life ruled, and the sun was significantly dimmer than it is today. Yet the rock record shows that vast seas covered much of the early Earth under the faint young sun.
Scientists have long debated what kept those seas from freezing. A popular theory is that potent gases such as methane – with many times more warming power than carbon dioxide – created a thicker greenhouse atmosphere than required to keep water liquid today.
In the absence of oxygen, iron built up in ancient oceans. Under the right chemical and biological processes, this iron rusted out of seawater and cycled many times through a complex loop, or “ferrous wheel.” Some microbes could “breathe” this rust in order to outcompete others, such as those that made methane. When rust was plentiful, an “iron curtain” may have suppressed methane emissions.
“The ancestors of modern methane-making and rust-breathing microbes may have long battled for dominance in habitats largely governed by iron chemistry,” said Marcus Bray, a biology Ph.D. candidate in the laboratory of Jennifer Glass, assistant professor in the Georgia Institute of Technology’s School of Earth and Atmospheric Sciences and principal investigator of the study funded by NASA’s Exobiology and Evolutionary Biology Program. The research was reported in the journal Geobiology on April 17, 2017.
Using mud pulled from the bottom of a tropical lake, researchers at Georgia Tech gained a new grasp of how ancient microbes made methane despite this “iron curtain.”
Collaborator Sean Crowe, an assistant professor at the University of British Columbia, collected mud from the depths of Indonesia’s Lake Matano, an anoxic iron-rich ecosystem that uniquely mimics early oceans. Bray placed the mud into tiny incubators simulating early Earth conditions, and tracked microbial diversity and methane emissions over a period of 500 days. Minimal methane was formed when rust was added; without rust, microbes kept making methane through multiple dilutions.
Extrapolating these findings to the past, the team concluded that methane production could have persisted in rust-free patches of ancient seas. Unlike the situation in today’s well-aerated oceans, where most natural gas produced on the seafloor is consumed before it can reach the surface, most of this ancient methane would have escaped to the atmosphere to trap heat from the early sun.
In addition to those already mentioned, the research team included Georgia Tech professors Frank Stewart and Tom DiChristina, Georgia Tech postdoctoral scholars Jieying Wu and Cecilia Kretz, Georgia Tech Ph.D. candidate Keaton Belli, Georgia Tech M.S. student Ben Reed, University of British Columbia postdoctoral scholar Rachel Simister, Indonesian Institute of Sciences researcher Cynthia Henny, Skidaway Institute of Oceanography professor Jay Brandes, and University of Kansas professor David Fowle.
This research was funded by NASA Exobiology grant NNX14AJ87G. Support was also provided by a Center for Dark Energy Biosphere Investigations (NSF-CDEBI OCE-0939564) small research grant, and by the NASA Astrobiology Institute (NNA15BB03A). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsoring organizations.
CITATION: Bray M.S., J. Wu, B.C. Reed, C.B. Kretz, K.M. Belli, R.L. Simister, C. Henny, F.J. Stewart, T.J. DiChristina, J.A. Brandes, D.A. Fowle, S.A. Crowe, J.B. Glass. 2017. "Shifting microbial communities sustain multi-year iron reduction and methanogenesis in ferruginous sediment incubations," (Geobiology 2017). http://dx.doi.org/10.1111/gbi.12239.
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The College of Sciences held its annual summer dinner on Aug. 23, 2016. The festive occasion welcomed new faculty members and recognized excellence in research, teaching, and service.
College of Sciences Dean Paul M. Goldbart welcomed colleagues joining the College in the 2016-17 academic year: Tamara Pearson and Lorna Rivera, in CEISMC; Will Gutekunst and Henry La Pierre, in the School of Chemistry and Biochemistry; Liang Han, Colin Harrison, and Frank Rosenzweig, in the School of Biological Sciences; Jennifer Hom, Christopher Jankowski, Lutz Warnke, and Mayya Zhilova, in the School of Mathematics; and Elisabetta Matsumoto and Colin Parker, in the School of Physics.
Goldbart also recognized J. Todd Streelman, the new chair of the School of Biological Sciences, which emerged on July 1, 2016, from the reorganization of the former School of Applied Physiology and School of Biology. Goldbart acknowledged T. Richard Nichols and Terry Snell, chairs of the former schools, for their efforts in launching the new school.
Celebrating excellence in research, teaching, and service was the evening’s center piece, beginning with the 2016 Faculty Mentor Awards to Luca Dieci, of the School of Mathematics; Facundo M. Fernandez, of the School of Chemistry and Biochemistry; and Rodney J. Weber, in the School of Earth and Atmospheric Sciences.
Carrie G. Shepler, of the School of Chemistry and Biochemistry, received the 2016 Eric R. Immel Memorial Award for Excellence in Teaching. The award is made possible by School of Mathematics alumnus Charles J. Crawford.
The 2016 Cullen-Peck Faculty Fellowship Awards in the College of Sciences went to Tamara Bogdanovic, of the School of Physics; Andrew V. Newman, of the School of Earth and Atmospheric Sciences; and Frank J. Stewart and Lewis A. Wheaton, of the School of Biological Sciences. These awards are made possible by the generosity of School of Mathematics alumni couple Frank H. Cullen and Libby Peck.
Daniel Margalit was celebrated as the inaugural 2016 Leddy Family Faculty Fellow. The award is made possible by the generosity of School of Physics alumnus Jeffrey Leddy and his wife, Pamela.
“It is invigorating to start the school year by warmly welcoming new colleagues into our scholarly community and celebrating our outstanding teachers, researchers, and mentors,” Goldbart said. “We are proud to have so many exceptional faculty members, and I am especially grateful for the generosity of our thoughtful alumni, which makes it possible for the College to enable our colleagues to achieve the highest level of success in their teaching, research, and service.”
More photos from the 2016 summer dinner can be viewed at http://bit.ly/2bz1Is8.
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Remnants of extinct monkeys are hiding inside you, along with those of lizards, jellyfish and other animals. Your DNA is built upon gene fragments from primal ancestors.
Now researchers at the Georgia Institute of Technology have made it more likely that ancestral genes, along with ancestral proteins, can be confidently identified and reconstructed. They have benchmarked a vital tool that would seem nearly impossible to benchmark. The newly won confidence in the tool could also help scientists compute ancient gene sequences and use them to synthesize better proteins to battle diseases.
For some 20 years, scientists have used algorithms to compute their way hundreds of millions of years back into the evolutionary past. Starting with present-day gene sequences, they perform what’s called ancestral sequence reconstruction (ASR) to determine past mutations and figure out the genes’ primal forerunners.
“With the help of ASR, we can now actually build those ancient genes in the laboratory and express their encoded ancient proteins,” said Eric Gaucher, an associate professor at Georgia Tech’s School of Biological Sciences. In a separate project, his lab is computing ancient proteins that were very effective in blood clotting 80 million years ago, in hopes of using them to fight hemophilia today.
That protein comes from a common ancestor humans share with rats.
Time travel substitute
But ASR algorithms have faced logical criticism. Species based on those primal genes are long extinct, and scientists can’t travel back in time to observe mutations that have happened since. So, how can anyone find any physical benchmark to verify and gauge ASR?
A team of researchers led by Gaucher did it by building an evolutionary framework out of myriad mutations. Then they benchmarked ASR algorithms against it – no time machine required. Their results have shored up confidence that the widely used algorithms are working as they should.
“Most of them did a very good job – 98% accurate,” Gaucher said of contemporary algorithms’ ability to compute ancient gene sequences. Their determination of proteins encoded by those sequences was virtually perfect.
Gaucher, research coordinator Ryan Randall and undergraduate student Caelan Radford published their results on Thursday, September 15, 2016, in the journal Nature Communications. Their research has been funded by the NASA Exobiology program, E.I. du Pont de Nemours and Company (DuPont) and the National Science Foundation.
Holographic tree branches
Ancestral sequence reconstruction is like making a family tree for genes.
The many twigs and branches at the treetop would be sequences from species alive today. Shimmying down the tree, called a phylogeny in genetics, you would find their common ancestors, millions of years old, in the lower branches.
There’s a caveat; none of the lower branches exist any longer. They vanished in the extinction of the species bearing those genetic sequences.
ASR computes them back into place using algorithms based on scientific models of evolution. It’s like replacing missing branches with holographic duplicates.
Algorithm horse race
The accuracy of those evolutionary models has been a historic sticking point. And doubts about the algorithms based on them linger in some circles that hold on to an old, tried-and-true algorithm.
So, Gaucher and researcher coordinator Randall pitted the contemporary model-based, or “maximum likelihood,” algorithms in a race against the generic, or “parsimony,” algorithm.
“Parsimony follows the simplest notion of evolution, which is that very little mutation occurs,” Randall said. The models behind contemporary “maximum likelihood” algorithms, by contrast, are laced with filigree, data-packed details.
For the race, Randall made a track of sorts by putting a gene sequence that made a single protein through multiple mutations to construct a real-life phylogeny. She used methods that closely mimicked natural evolution, but that were much, much faster.
Rainbow phylogeny racetrack
In cells, enzymes called polymerases aid in DNA duplication. They work very efficiently, but their rare mistakes are the most common source of mutations, and Randall took her lead from this.
“We used a polymerase that is error-prone to speed up mutations, and speed up evolution,” she said.
The genes used at the starting point of the lab evolution made a protein that fluoresced red when placed in bacteria. As significant mutations arose, the proteins began changing color. Bacteria containing green fluorescing proteins popped up among the red ones.
Randall divided bacteria with major mutations into new groups, creating branches in the phylogeny, as she went. Many mutations produced new colors – yellow, orange, blue, pink – and Randall ended up with a gene family tree in rainbow colors.
Show me the phenotype
The colors reflected not only new gene sequences but also new phenotypes – the actual proteins they produced, the organism’s working molecules.
“What counts is phenotype,” Gaucher said. “When you analyze DNA strictly by itself, it ignores the context, in which that DNA is connected to phenotype,” he said.
DNA can mutate and still encode the same amino acids, protein’s component parts. Then the mutation has no real effect. But when mutations cause DNA to encode different amino acids, they’re more significant.
A worthy test of ancestral sequence reconstruction algorithms must therefore include phenotype. And Randall took this into account when she selected mutated proteins.
“I selected for variants to purposely make it hard on the algorithms to infer the phenotypes,” she said. The race ensued, and the algorithms got limited information to infer the evolutionary tree’s many dozens of past mutations.
ASR a sure bet
Though the tried-and-true parsimony algorithm performed well, maximum likelihood performed better. “Even though it got the same number of residues (DNA sequences) wrong as parsimony, the incorrectly inferred sequences were still more likely to encode the right phenotypes,” said undergraduate student Caelan Radford, who analyzed the experiment’s statistics.
The margin of error was so tiny that it would not interfere in the determination of past species.
The experiment’s outcome was not too surprising, because prior simulations had predicted it. But the researchers wanted the scientific community to have physical proof that feels trustier than proof from a computer. “It’s a computer algorithm. It will do what you will tell it to do,” Gaucher said.
Short history of ASR
Doubts about ancestral sequence reconstruction -- and maximum likelihood algorithms in particular -- go far back. The idea of performing ASR first came up in 1963, but it didn’t get started until the 1990s, and back then, researchers battled fervently over wide-ranging methods.
“People would come up with the craziest notion as to why one model was best,” Gaucher said. “They’d say, ‘Well, if I simulate this weird mode of evolution along these branches here, my algorithm will work better than your algorithm.’”
The parsimony algorithm was a way of reigning in the chaos that grew out of a lack of data in evolutionary models at the time. “When the model is wrong, ‘maximum likelihood’ fails miserably,” Gaucher said.
But, now, a host of data and analysis give scientists a great picture of how evolution works (and it’s not a parsimony principle): For ages, nothing moves, then change bursts forth, then things stabilize again.
“You get this quick evolution, so lots of stuff works and lots of stuff fails, and the stuff that works then goes on and kind of maintains its status and doesn’t change,” Gaucher said. By confirming the high accuracy of the algorithms, the Georgia Tech team has also corroborated the validity of current evolutionary science they’re based on.
Kelsey Roof and Divya Natarajan of Georgia Tech coauthored the paper. Research was funded the NASA Exobiology program (grant number NNX12AI10G), DuPont (Young Professor Award) and the National Science Foundation (grant number 1145698). Any opinions, findings and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsoring agencies.
The lab of Greg Gibson at the Georgia Institute of Technology has been awarded a grant of $2.3 million to study the subtle genetic underpinnings of autoimmune-related diseases by taking a computational approach.
The National Institutes of Health made the award as part of an $11.1 million total investment in research funds slated for five institutions, including Georgia Tech. The researchers’ work could increase understanding of the causes of diabetes, Crohn’s disease, rheumatoid arthritis, forms of heart disease, and more afflictions where inflammation is at issue, and where there may be a connection to autoimmunity.
"We know that hundreds of genes impact autoimmunity, but the challenge is to narrow down the actual DNA sequence changes that have an impact. This grant combines our statistical genetics expertise with evolutionary genetics and genome editing by collaborators,” said Greg Gibson, a professor at Georgia Tech’s School of Biological Sciences.
In its research, Georgia Tech will work together with Rice University in Houston and Temple University in Philadelphia. Gibson's researchers will handle statistical analysis and interpretation; Rice's scientists will carry out gene editing, and evolutionary geneticists at Temple will contribute insights on which gene sites should or should not be variable in the human genome.
Attacking friends: Autoimmunity
Our cells work together with masses of microbes that are an integral part of the human body, but the immune systems of people with related diseases can attack the microbes and healthy human cells, and lead to inflammation. “Lymphocytes, for example, could be attacking the body,” Gibson said.
“We’re looking at genes that regulate the immune system,” he said. “They’ve all got subtle effects. What counts is that they all work together. We’re looking for sections of genetic code that work a little oddly.”
Researchers will put data through algorithms to better identify genetic variants in sections of the human genome that do not encode proteins, but have regulatory functions, the NIH said in a news release. These are sections of DNA that, for example, turn encoding genes on and off.
Subtleties multiplied: Susceptibility
They have been lesser studied but are known to be critical and could provide new information on yet undiscovered pathways composed of multiple faint characteristics that add up to disease.
"Taken alone, some small characteristic may appear indistinct, and at the same time, it’s really hard to read how a big group of them work in total,” Gibson said. “But their cumulative effect is dramatic, and unfortunate.”
Recent genomic research methods have compared the complete genomes of patients with diseases to those without them, leading to thousands of statistical hints. Now new data and interpretive approaches are needed to effectively sift through these to see the foundations of diseases, or make predictions of who is most at risk, and what people can do to reduce the risk.
The NIH hopes statistical methods will allow prediction of possible effects some variants have on susceptibility to disease and on drug response. The funding comes from the NIH’s National Human Genome Research Institute (NHGRI)'s Non-Coding Variants Program, and the National Cancer Institute (NCI).
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.
The Petit Institute for Bioengineering and Bioscience has grown again with the addition of five new faculty researchers, four of them based in the Wallace H. Coulter Department of Biomedical Engineering (BME), a joint department of the Georgia Institute of Technology and Emory University.
Joining the multidisciplinary research institute are Jaydev Desai, Scott Hollister, Frank Rosenzsweig, Kalid Salaita, and Annabelle Singer.
Desai joined the Coulter Department this past summer as a professor and BME Distinguished Faculty Fellow. Former director of the Robotics, Automation, and Medical Systems (RAMS) Laboratory at the University of Maryland, Desai’s research interests are focused primarily on image-guided surgical robotics, rehabilitation robotics, cancer diagnosis at the micro scale, and grasping.
Holister comes to the Coulter Department from the University of Michigan, where he directed the Scaffold Tissue Engineering Group, which develops degradable scaffold material systems, which can be used to deliver stem cells, genes and proteins to regenerate tissue defects, leading to clinical applications that include include spine fusion and disc repair, craniomaxillofcial reconstruction, orthopaedic trauma and joint reconstruction, and cardiovascular reconstruction.
Rosenzweig, a professor in the School of Biological Sciences, spent the past 15 years at the University of Montana in Missoula. The underlying goal of his research is to enlarge our understanding of the ecological and evolutionary forces that promote and preserve genetic variation, studying how genetic variation is integrated at the level of cellular physiology to produce differences in fitness.
Salaita, an assistant professor in BME based at Emory since 2009 who was previously a postdoctoral fellow at the University of California-Berkeley, is principal investigator of a wide-ranging research group that develops chemical tools to better understand how chemical and physical signals are transmitted in living systems.
Singer is an assistant professor of BME, where her lab group works on uncovering how complex patterns of activity across populations of neurons are decoded to guide behavior in health and disease, using a combination of novel tools, including robotic patch clamp recordings, large-scale extracellular recordings, cutting edge data analysis methods, new behavioral paradigms, and novel brain stimulation tools.
Now with more than 180 faculty researchers, the Petit Institute is an internationally recognized hub of multidisciplinary research, where engineers and scientists are working on solving some of the world’s most challenging health issues. With 18 research centers and more than $24 million invested in state-of-the-art core facilities, the Petit Institute is translating scientific discoveries into game-changing solutions to solve real-world problems.
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A vision recently came to researcher Will Ratcliff about the scientific legacy he’d like to look back on 30 years from now.
The moment of clarity was fueled by an award from the David and Lucile Packard Foundation, which this week named Ratcliff a Packard Fellow for 2016. The prestigious fellowship has freed the evolutionary biologist’s mind to think beyond the previous horizons of his lab’s experimental goals.
Packard formally announced on Friday, October 14, that the annual fellowship was being awarded to 18 scientists nationwide. They will receive $875,000 each, paid out over a five-year period.
Ratcliff, who studies the evolution of single-cell organisms into multicellular groups at the Georgia Institute of Technology, found out he was one of the recipients a few days prior. And when he did, it sent his head reeling.
“The first night after I heard about it, I had these waves of thoughts like, ‘Hey, we could do this cool experiment!’” he said. “Then I’d go to bed and another one would jolt me awake, ‘Woah, and we could do this!’”
Fast-forward movie of life
Since then, a legacy goal has crystalized. “I want us to rewind the tape of life and watch it on fast-forward,” he said.
“I want to see how unicellular organisms evolve into bona fide multicellular organisms with robust division of labor, and multiple cell types. I want to see how development evolves from scratch,” said the assistant professor at Georgia Tech’s School of Biological Sciences.
Ratcliff has gained notoriety among biologists for producing conditions that have accelerated the evolution of yeast and algae cells from single cells into cell clusters that then grow in complexity and begin to specialize in cell function. One of his signature achievements is yeast cell groups called “snowflakes.”
In August, two months before the Packard announcement, the magazine Popular Science recognized Ratcliff in its annual list “The Brilliant 10,” which applauds a select group of up-and-coming scientists and engineers.
PopSci cited his work demonstrating how an evolutionary leap may have occurred that was key to the advent of plants and animals, but also arduous, since single cells had to forfeit much of their own fitness for the greater good of creating viable cell groups.
Evolutionary long game
Ratcliff thinks he may be able to shepherd a recapitulation of the evolutionary path that led to first complex beings within his lifetime by hyper-accelerating natural selection in the lab. And he believes the accomplishment would be valuable to science for a long time to come.
“We’ve never actually seen that process in real time,” Ratcliff said. “I want to put that movie of the tape of life on fast-forward in my laboratory to be able to understand the general rules that govern this evolutionary process. It would have profound implications of how complex life arises not just on Earth, but also elsewhere in the universe.”
Ratcliff says the Packard Fellowship will allow him to take the long view, and not only due to the award’s ampleness. “It’s very flexible in that they want you to be creative and feel free to pursue the research you find most exciting.”
Unlike most grants, this one’s not tied to specific research milestones.
“It’s designed to nurture you,” Ratcliff said. “They’re investing in the researcher, and as a result, I’m stepping back and taking stock of my research thinking in a way I never have before,” he said.
Legacy research in future science
Ratcliff sees the fellowship as an opportunity to make an impactful contribution to evolutionary science, and has been inspired by the work of biologist Rich Lenski at Michigan State University.
Lenski has run a 28-year experiment viewed as classic in the field, evolving of E. coli bacteria in the lab for nearly 60,000 generations. The work has been an endless source of information and created a continuing legacy.
“One of the great things about experimental evolution is that you can create a living record of the entire experiment by live-archiving your populations in the freezer at regular intervals,” Ratcliff said. As decades pass, scientific and technological advances come along and allow researchers to exponentially boost the usefulness of that archive.
“In Lenksi’s experiment, for example, the recent revolution in genome sequencing means that they can examine the evolutionary dynamics of his entire experiment in ways they never would have expected,” Ratcliff said.
Ratcliff envisions using some of the Packard funding to establish evolutionary lines that he would continue throughout his career. “Hopefully for 20 or 30 years,” he said. “I’d love to take these simple multicellular things we have already and push them to see how complex we can actually get them.”
He would like to end up with a library of simple multicellular beings across multiple evolutionary phases.
Georgia Tech collaboration
But before he lays down details, Ratcliff wants to consult with his collaborators, particularly Georgia Tech physicist Peter Yunker. He’s been helping Ratcliff solve problems that organisms encounter as they become more complex.
“We’re looking at the materials properties of our (yeast) snowflakes,” Ratcliff said. “Evolving novel physical properties – bodies with specific functionality – is an often overlooked but major challenge facing nascent multicellular critters.”
Working with scientists from a different discipline has changed Ratcliff’s perspective by creating thought synergies, a legendary Georgia Tech strength. “The level of collaboration here is really unreal, actually,” Ratcliff said.
“From the president through the ranks, there is an ethos of collaboration,” he said. “That helps the science be better in the long term.”
A rare honor shared
A Packard Fellowship is a rare honor that starts with the foundation narrowing down to 50 the number of universities prompted to provide applicants. The universities are then instructed to nominate two scientists each, who write a two-page research proposal describing their future work.
“My faculty advisor told me, ‘This may be the most important two pages of your life,’” Ratcliff said. “I took that to heart and spent close to a month only writing the proposal.”
And he reached out to colleagues for help.
“I’m pretty confident that I wouldn’t have gotten it, if we didn’t have so many smart faculty here who are so eager to collaborate. I got feedback from about a dozen colleagues in the School, and that made the proposal stronger.”
Disclaimer: Any opinions, findings and conclustions or recommendations expressed in this material are those of the author(s) and/or researcher(s) and do not necessarily reflect the views of any sponsoring agencies.
Mary Beth Brown came to Georgia Tech to do research in Applied Physiology. She attended the School of Applied Physiology and received a Ph.D. in 2009. The school is now the School of Biological Sciences after a reorganization in July 2016.
Before Georgia Tech, Brown attended St. Petersburg High School, in St. Petersburg, Florida. She received a B.A. in Exercise Science from Lenoir-Rhyne University, in North Carolina, and an M.S. in Physical Therapy from the University of Miami, in Florida. She practiced as a physical therapist for almost 10 years prior to returning to school to pursue her Ph.D.
After completing her Ph.D., Brown took a postdoctoral fellowship at Indiana University School of Medicine, in Indianapolis, where she currently lives. Brown is now an assistant professor of physical therapy in the School of Health and Rehabilitation Sciences at Indiana University.
What attracted you to study in Georgia Tech?
The Applied Physiology program and the opportunity to be under the guidance of Dr. Mindy Millard-Stafford in her Exercise Physiology Lab seemed like a good fit for my interests and background. Being in downtown Atlanta was exciting.
Georgia Tech, the Applied Physiology program, and its faculty met my expectations. Most importantly, I learned how to be a good researcher. As a Ph.D. student, that’s what I came to learn.
What is a vivid memory of your time at Georgia Tech?
Getting to deliver my Ph.D. dissertation presentation after four+ years of work on my topic was one of the biggest thrills of my life, and highly gratifying.
How did you get to your current position?
I took a postdoctoral fellowship position at Indiana University School of Medicine after completing my Ph.D. at Georgia Tech. Then a research tenure-track faculty position opened up in Indiana University, in the Physical Therapy department, where I wanted to be. It worked out perfectly.
What roles did your Georgia Tech education and experience play in your journey to your current position?
I had tremendous education in research. Much of this was out of the classroom. But the foundation was laid in the classroom. Also, my Ph.D. program’s willingness to support and encourage the collaboration I wanted to do with Emory School of Medicine permitted me to pursue my research question with greater breadth and depth, and that took it from being good to great. More importantly, it helped me fill my investigator tool box with many more tools to which I may not have had exposure otherwise.
Which professor(s) or class(es) made a big impact on your career path?
I teach physiology now, so my physiology courses at Georgia Tech (Systems Physiology I, II, and III) made a big impact. I particularly was influenced by Dr. Tom Burkholder, who taught the first of these courses, as well as an outstanding muscle physiology course.
Another course that was also impactful was Foundations in Molecular and Cell Biology, BIOL 7001. It was invented and directed by Dr. Nael McCarty, with contributions from many guest lecturing principal investigators from the School of Biology (now also the School of Biological Sciences). That class was one of the most challenging of my time at Georga Tech, but probably influenced my career path more than any other class, in a positive way.
What do you like most about your current job? The least?
The most: working with students in my lab. The least: faculty meetings.
What has been the greatest challenge in your professional life so far?
Learning to accept rejection is probably the greatest challenge, and it is not just a one-time event. It happens repeatedly as a researcher. Rejected grant applications, rejected manuscripts—it is hard in the beginning, and this is where more senior colleagues are helpful to provide perspective.
I have learned that it helps to take a LOT of shots at the goal. Rejections are common, even for good products. The trick is to keep submitting, keep learning from them, and keep evolving.
What has been the most gratifying experience of your professional career so far?
The most gratifying so far was my first NIH funding award, last year. It gave me the confidence to keep at it, even when things seemed to be going every way except my way in my research.
The second most gratifying was this year when I came back and gave a research talk at Georgia Tech to my former professors and current and past students of the School of Applied Physiology. It was not just an honor; it was gratifying in that I felt like it was a true, from-the-heart ‘thank you’ to them from me for the important role they played in my career path.
If you could have taken an alternative career path, what would you be doing instead?
Okay, maybe a professional surfer. I can’t even surf, never tried, but those women look so cool and so fearless.
What advice would you give to incoming first-year students at Georgia Tech?
To first-year Ph.D. students at Tech, I’d say be open-minded to immense possibilities. This can happen only if you get out of your comfort zone. When constructing your research projects, do not propose to study what you already know. Make sure your proposal really stretches you.
What’s something about yourself that’s not obvious to your colleagues?
I work as hard in my recreational sports endeavors as I do with my professional endeavors, and that’s because I am competitive probably to a fault. There is no just-for-fun race. I’ve taken to long, solo, endurance events (open-water swimming, marathons, ultra-distance triathlons), probably because these activities keep me from being too hard on anyone but myself.
If you could have dinner with any person from history, whom would you invite?
Hatshepsut, the woman who ruled Egypt as pharaoh starting around 1478 BC. She was feminism before feminism was even a thing. In this election year, when we are witnessing history with our first female presidential candidate, I am in complete disbelief that it has taken this long for this day to arrive. I’d like to ask Hatshepsut if she has any ideas about why this is so.
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