The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, has awarded a five-year contract of up to $19.4 million, depending on contract options exercised, to establish the Malaria Host-Pathogen Interaction Center (MaHPIC).
The consortium includes researchers at Emory University, with partners at the Georgia Institute of Technology, University of Georgia (UGA) and the Centers for Disease Control and Prevention (CDC). The Yerkes National Primate Research Center of Emory University will administer the contract.
The MaHPIC team will use the comprehensive research approach of systems biology to study and catalog in molecular detail how malaria parasites interact with their human and animal hosts. This knowledge will be fundamental to developing and evaluating new diagnostic tools, antimalarial drugs and vaccines for different types of malaria. The project will integrate data generated by malaria research, functional genomics, proteomics, lipidomics and metabolomics cores via informatics and computational modeling cores.
MaHPIC combines Emory investigators’ interdisciplinary experience in malaria research, metabolomics, lipidomics and human and non-human primate immunology and pathogenesis with UGA’s expertise in pathogen bioinformatics and large database systems, and Georgia Tech’s experience in mathematical modeling and systems biology. The CDC will provide support in proteomics and malaria research, including nonhuman primate and vector/mosquito infections.
The principal investigator is Mary Galinski, PhD, professor of medicine, infectious diseases and global health at Emory University School of Medicine and director of Emory’s International Center for Malaria Research, Education & Development (ICMRED). She has been leading malaria research projects at the Emory Vaccine Center and Yerkes for 15 years.
“We are thankful to the National Institute of Allergy and Infectious Diseases for recognizing the enormous potential of taking a systems biology approach to studying malaria infections,” Galinski says.
“This project will help us better understand malaria as a disease in depth and pave the way for new preventive and therapeutic measures. We expect to provide a groundbreaking wealth of information that will address current challenges in fighting malaria. The Georgia team we have assembled is outstanding and we also look forward to working closely with prominent international partners from malaria endemic countries.”
A prestigious international Scientific Consultation Group is also involved, and met with the MaHPIC team at Emory recently, following the annual American Society of Tropical Medicine and Hygiene conference held in Atlanta.
The MaHPIC project involves studying both nonhuman primate infections and clinical samples from humans around the world. For the study of malaria, “systems biology” means first collecting comprehensive data on how a Plasmodium parasite infection produces changes in host and parasite genes, proteins, lipids, the immune response and metabolism.
Computational researchers will then design mathematical models to simulate and analyze what’s happening during an infection and to find patterns that predict the course of the disease and its severity. Together, the insights will help guide the development of new interventions. Co-infections and morbidities will also come into play, as well as different cultural and environmental backgrounds of the communities involved.
The team will use metabolomics techniques that will allow scientists to detect, analyze and make crucial associations with thousands of chemicals detectable in the blood via mass spectrometry. The techniques were developed at Emory by Dean Jones, PhD, professor and director of the Clinical Biomarkers Laboratory and MaHPIC’s metabolomics core leader.
“This is a wonderful opportunity to integrate multiple types of rich biological data into dynamic models that will help scientists around the world devise novel strategies to help control not just malaria but other infectious diseases,” says Greg Gibson, PhD, professor and director of the Center of Integrative Genomics at Georgia Tech.
“MaHPIC will generate experimental, clinical and molecular data associated with malaria infections in nonhuman primates on an unprecedented scale,” says Jessica Kissinger, PhD, who will direct the project’s informatics team. Kissinger is professor of genetics at UGA and director of UGA’s Institute of Bioinformatics.
“In addition to mining the massive quantities of integrated data for trends and patterns that may help us understand host and pathogen interaction biology, we may identify potential targets for early and species-specific diagnosis of malaria, which is critical for proper treatment,” Kissinger says.
The MaHPIC team will develop an informative public website and specialized web portal to share the project’s data and newly developed data analysis tools with the scientific community worldwide.
“The sheer amount of detailed, high-quality information amassed by the experimental groups will be unprecedented. With this project we have an incredible opportunity to integrate data with modern computational tools of dynamic modeling,” says Eberhard Voit, PhD, professor of biomedical engineering and cofounder of the Integrative BioSystems Institute at Georgia Tech. “This integration will allow us to analyze the complex networks of interactions between hosts and parasites in a manner never tried before. Systems biology will be the foundation for this integration.”
Georgia Tech's involvement:
Greg Gibson, PhD, professor and director of the Center of Integrative Genomics, will be the director of the functional genomics core. Eberhard Voit, PhD., professor and David D. Flanagan Chair in biological systems, Georgia Research Alliance Eminent Scholar, and cofounder of the Integrative BioSystems Institute, will be the director of the computational modeling core. Mark Styczynski, an assistant professor in Chemical & Biomolecular Engineering, will serve as deputy director of the computational modeling core.
New research from Georgia Aquarium and Georgia Institute of Technology provides evidence that a suite of techniques called “metabolomics” can be used to determine the health status of whale sharks (Rhincodon typus), the world’s largest fish species. The study, led by Dr. Alistair Dove, director of Research & Conservation at Georgia Aquarium and an adjunct professor at Georgia Tech, found that the major difference between healthy and unhealthy sharks was the concentration of homarine in their in serum—indicating that homarine is a useful biomarker of health status for the species.
The paper, “Biomarkers of whale shark health: a metabolomic approach”, which is published in the journal PLOS ONE, is especially significant to the veterinary science community because the study documents the results of a rare opportunity to collect and analyze blood from whale sharks. The paper also comprises the only work yet carried out on biochemistry of the world’s largest fish.
“This research and its resulting findings are vitally important to ensuring Georgia Aquarium’s and the scientific community’s care, knowledge, and understanding of not only whale sharks, but similar species of sharks and rays,” said Dr. Greg Bossart, Senior Vice President of Animal Health, Research & Conservation and Chief Veterinary Officer at Georgia Aquarium. “The publishing of this clinical research provides a greater opportunity for scientists and Zoological professionals to understand the Animals in our care and can be used to help wild populations, which puts us ahead of the curve in the integrated understanding of animal biology.”
Previous research and observations showed that traditional veterinary blood chemistry tests were not as useful with whale sharks; most likely because such tests are designed for mammals and comparatively less is known about shark and ray blood. Dr. Dove and six colleagues from Georgia Tech set out to significantly increase knowledge of whale shark biochemistry by examining the metabolite composition of all six whale sharks which have been cared for at Georgia Aquarium. By using metabolomics, the researchers were able to determine which chemical compounds were present in the shark blood, without knowing ahead of time what they are.
“It is vitally important for us to continue to learn how to best support the whale sharks in our care,” said Dove, who, along with the GA Tech team, spent three years developing the research. “We began the study by asking ourselves, ‘What should we be looking for in whale shark serum?’ and ‘What compounds in serum might best indicate the health status of whale sharks?’”
Not only did the study determine that metabolic profiles of unhealthy whale sharks were markedly different than those of healthy sharks in general and particularly the different levels of homarine, but the research team also identified more than 25 other compounds that differed in concentration based on the health of the individual.
Findings detailed in “Biomarkers of whale shark health: a metabolomic approach” will help scientists and veterinarians to better understand the biology of whale sharks in their natural setting, and by homology, the biology of other shark and ray species that may be similar. Further, data compiled in the research will provide a reference library about whale shark biochemistry that can be consulted in future studies and importantly, adds new knowledge that will be useful to those who care for sharks and rays on a daily basis.
“This sort of advanced research is only made possible through collaboration between aquarium scientists and experts at our partner universities,” said Dr. Dove.
The research team included, from Georgia Tech: Dr. Johannes Leisen, research scientist; Dr. Manshi Zhou, post-doctoral candidate; Dr. Jonathan Byrne, post-doctoral candidate; Krista Lim-Hing, student; Dr. Leslie Gelbaum, Dr. Mark Viant, Dr. Julia Kubanek, and Dr. Facundo Fernandez; and from Georgia Aquarium: Harry D. Webb, research technician. Additional support also came from Georgia Tech’s National Science Foundation (NSF) undergraduate research program in mathematical biology.
Written by Stephanie Johnson, senior public relations specialist at Georgia Aquarium.
If the 4.9 million barrels of oil that spilled into the Gulf of Mexico during the 2010 Deep Water Horizon spill was a ecological disaster, the two million gallons of dispersant used to clean it up apparently made it even worse – 52-times more toxic. That’s according to new research from the Georgia Institute of Technology and Universidad Autonoma de Aguascalientes (UAA), Mexico.
The study found that mixing the dispersant with oil increased toxicity of the mixture up to 52-fold over the oil alone. In toxicity tests in the lab, the mixture’s effects increased mortality of rotifers, a microscopic grazing animal at the base of the Gulf’s food web. The findings are published online by the journal Environmental Pollution and will appear in the February 2013 print edition.
Using oil from the Deep Water Horizon spill and Corexit, the dispersant required by the Environmental Protection Agency for clean up, the researchers tested toxicity of oil, dispersant and mixtures on five strains of rotifers. Rotifers have long been used by ecotoxicologists to assess toxicity in marine waters because of their fast response time, ease of use in tests and sensitivity to toxicants. In addition to causing mortality in adult rotifers, as little as 2.6 percent of the oil-dispersant mixture inhibited rotifer egg hatching by 50 percent. Inhibition of rotifer egg hatching from the sediments is important because these eggs hatch into rotifers each spring, reproduce in the water column, and provide food for baby fish, shrimp and crabs in estuaries.
“Dispersants are preapproved to help clean up oil spills and are widely used during disasters,” said UAA’s Roberto-Rico Martinez, who led the study. “But we have a poor understanding of their toxicity. Our study indicates the increase in toxicity may have been greatly underestimated following the Macondo well explosion.”
Martinez performed the research while he was a Fulbright Fellow at Georgia Tech in the lab of School of Biology Professor Terry Snell. They hope that the study will encourage more scientists to investigate how oil and dispersants impact marine food webs and lead to improved management of future oil spills.
“What remains to be determined is whether the benefits of dispersing the oil by using Corexit are outweighed by the substantial increase in toxicity of the mixture,” said Snell, chair of the School of Biology. “Perhaps we should allow the oil to naturally disperse. It might take longer, but it would have less toxic impact on marine ecosystems.”
Researchers in the School of Biology at Georgia Tech have uncovered a novel mechanism of genome mutagenesis and remodeling that could help to explain abnormal DNA amplification in cancer and other degenerative disorders. Cancer and other degenerative disorders are commonly associated with abnormal DNA amplification (resulting in an increase in the number of copies of a DNA segment) in various locations throughout the genome. These mutations can facilitate the aggressiveness of cancer to the detriment of human health and are therefore of great scientific interest. Kuntal Mukherjee, former postdoctoral fellow in the lab of Francesca Storici, developed an approach to capture the events of DNA amplification driven by small pieces of DNA in yeast cells and provided initial characterization of the mechanism. The discovery, published this week in PLoS Genetics (http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003119), reveals that small pieces of DNA can be potent inducers of gene amplification and genomic rearrangement.
Small DNA fragments can form as byproducts of DNA metabolism, reverse transcription or DNA degradation. In addition after cells lyse, or undergo apoptosis, these fragments (or DNA debris) can be released into extracellular space and taken up by neighboring cells. Due to complementarity, the small DNA fragments can direct specific amplification events in homologous chromosomal regions, resulting in Small Fragment-driven DNA Amplification (SFDA). Mukherjee and Storici demonstrate that SFDA results in tandem chromosomal duplications or formation of extrachromosomal circles that mimic the DNA amplification structures commonly found in many cancer cells. Prominent examples of these mutations in cancer include the repeated units clustered at a single chromosomal locus (homogeneously staining regions) and the circular extrachromosomal elements replicating autonomously and lacking a centromere and telomeres (double minutes).
The implications of their discovery suggest that DNA debris could potentially spread chromosomal rearrangements from one cell to another like ‘infectious’ agents. Considering that DNA fragments are highly recombinogenic and also highly abundant in cells, the researchers propose that SFDA could be a common mechanism of DNA amplification-driven carcinogenesis, as well as a more general cause of DNA copy number variation in nature.
This project was supported by the Georgia Cancer Coalition grant (award R9028).
When you walk into Brian Hammer’s classroom, you might be greeted by the sounds of hip-hop artist Nicki Minaj or the Godfather of Soul James Brown. It all depends on the day’s lecture.
“Before class, I play a song that is related to what I’ll be discussing,” said Hammer, an assistant professor in the School of Biology. “For example, if we are talking about how genes are activated, I might play David Guetta and Nicki Minaj’s ‘Turn Me On,’ or if I’m talking about bacteria transferring DNA, I might play ‘Sex Machine’ by James Brown.”
Music is one of the ways that Hammer, who arrived at Georgia Tech in 2008, tries to make often-complicated material understandable to students.
“My research focuses on concepts like cell-to-cell communication called ‘quorum sensing,’ which can be a challenge to wrap your brain around,” he said. “But I love the challenge of finding ways to explain my research to anyone — from my college students to my wife’s second graders.”
Read on to learn more about Hammer and his time at Tech.
How did you get to Tech?
While doing my post-doctoral work at Princeton University, I realized that I wanted to work at an institution that was supportive of an interdisciplinary approach to research. At Georgia Tech, biologists are integrated with engineers and that appealed to me.
Tell us about your research.
I study how bacteria use chemicals to communicate with their environments. For example, Vibrio cholerae, which causes the fatal disease cholera, lives in the ocean. When it comes into contact with chitin from crab shells, the chitin acts as a signal that flips an “on” switch in the bacteria. The cholera bacteria then start to bring in DNA from their environment that can provide the microbes with new genetic material, allowing them to, for example, make new toxins or other disease-causing factors.
What is an average day like for you?
I teach three days a week and then spend my remaining time doing office work, meeting with students and trying to inspire them, and presenting at meetings.
Name a misconception that people have about your profession.
A seventh grade teacher who I collaborate with each summer told me that he thought all microbiologists used microscopes — but we don’t. Actually, most of our days are spent using pipettes to dispense fluid containing DNA into tiny tubes.
What is the one piece of technology you couldn’t live without?
What is the greatest challenge you’ve faced while teaching?
Coming to the realization that all of my students aren’t little clones of me, meaning that the way I learned things and did research might not work for them. I’m always reminding myself to think of students like I think of my successful colleagues. Just because the students’ approaches are different from mine doesn’t mean they can’t be just as effective.
What do you think about the increasing popularity of massive open online courses?
I think we have to be open to them, because they are coming whether we like it or not. Personal interaction is important to me in my classes, and I think some of that will be lost in these courses. But I would be open to teaching one.
What is your favorite spot on campus?
I like the biotech quad. The grassy area is a quiet place, and I love the fact that I’m also surrounded by science.
Where is your favorite place to have lunch?
It would have to be Taqueria del Sol, and I’ll order enchiladas or fish tacos.
Tell us something unique about yourself.
When I was an undergraduate at Boston College, I sang in the university chorale and had the opportunity to sing for Pope John Paul II in St. Peter’s Basilica.
What was the greatest risk you ever took — and did it pay off?
While I was completing my master’s in ecology, it was difficult to admit that I didn’t know what I wanted to do with my life. It was a huge relief when I was able to admit this. I was finally able to figure out that microbiology was what I was interested in.
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The rise of antibiotic-resistant bacteria has initiated a quest for alternatives to conventional antibiotics. One potential alternative is PlyC, a potent enzyme that kills the bacteria that causes strep throat and streptococcal toxic shock syndrome. PlyC operates by locking onto the surface of a bacteria cell and chewing a hole in the cell wall large enough for the bacteria’s inner membrane to protrude from the cell, ultimately causing the cell to burst and die.
Research has shown that alternative antimicrobials such as PlyC can effectively kill bacteria. However, fundamental questions remain about how bacteria respond to the holes that these therapeutics make in their cell wall and what size holes bacteria can withstand before breaking apart. Answering those questions could improve the effectiveness of current antibacterial drugs and initiate the development of new ones.
Researchers at the Georgia Institute of Technology and the University of Maryland recently conducted a study to try to answer those questions. The researchers created a biophysical model of the response of a Gram-positive bacterium to the formation of a hole in its cell wall. Then they used experimental measurements to validate the theory, which predicted that a hole in the bacteria cell wall larger than 15 to 24 nanometers in diameter would cause the cell to lyse, or burst. These small holes are approximately one-hundredth the diameter of a typical bacterial cell.
“Our model correctly predicted that the membrane and cell contents of Gram-positive bacteria cells explode out of holes in cell walls that exceed a few dozen nanometers. This critical hole size, validated by experiments, is much larger than the holes Gram-positive bacteria use to transport molecules necessary for their survival, which have been estimated to be less than 7 nanometers in diameter,” said Joshua Weitz, an associate professor in the School of Biology at Georgia Tech. Weitz also holds an adjunct appointment in the School of Physics at Georgia Tech.
The study was published online on Jan. 9, 2013 in the Journal of the Royal Society Interface. The work was supported by the James S. McDonnell Foundation and the Burroughs Wellcome Fund.
Common Gram-positive bacteria that infect humans include Streptococcus, which causes strep throat; Staphylococcus, which causes impetigo; and Clostridium, which causes botulism and tetanus. Gram-negative bacteria include Escherichia, which causes urinary tract infections; Vibrio, which causes cholera; and Neisseria, which causes gonorrhea.
Gram-positive bacteria differ from Gram-negative bacteria in the structure of their cell walls. The cell wall constitutes the outer layer of Gram-positive bacteria, whereas the cell wall lies between the inner and outer membrane of Gram-negative bacteria and is therefore protected from direct exposure to the environment.
Georgia Tech biology graduate student Gabriel Mitchell, Georgia Tech physics professor Kurt Wiesenfeld and Weitz developed a biophysical theory of the response of a Gram-positive bacterium to the formation of a hole in its cell wall. The model detailed the effect of pressure, bending and stretching forces on the changing configuration of the cell membrane due to a hole. The force associated with bending and stretching pulls the membrane inward, while the pressure from the inside of the cell pushes the membrane outward through the hole.
“We found that bending forces act to keep the membrane together and push it back inside, but a sufficiently large hole enables the bending forces to be overpowered by the internal pressure forces and the membrane begins to escape out and the cell contents follow,” said Weitz.
The balance between the bending and pressure forces led to the model prediction that holes 15 to 24 nanometers in diameter or larger would cause a bacteria cell to burst. To test the theory, Daniel Nelson, an assistant professor at the University of Maryland, used transmission electron microscopy images to measure the size of holes created in lysed Streptococcus pyogenes bacteria cells following PlyC exposure.
Nelson found holes in the lysed bacteria cells that ranged in diameter from 22 to 180 nanometers, with a mean diameter of 68 nanometers. These experimental measurements agreed with the researchers’ theoretical prediction of critical hole sizes that cause bacterial cell death.
According to the researchers, their theoretical model is the first to consider the effects of cell wall thickness on lysis.
“Because lysis events occur most often at thinner points in the cell wall, cell wall thickness may play a role in suppressing lysis by serving as a buffer against the formation of large holes,” said Mitchell.
The combination of theory and experiments used in this study provided insights into the effect of defects on a cell’s viability and the mechanisms used by enzymes to disrupt homeostasis and cause bacteria cell death. To further understand the mechanisms behind enzyme-induced lysis, the researchers plan to measure membrane dynamics as a function of hole geometry in the future.
CITATION: Mitchell GJ, Wiesenfeld K, Nelson DC, Weitz JS, “Critical cell wall hole size for lysis in Gram-positive bacteria,” J R Soc Interface 20120892 (2013): http://dx.doi.org/10.1098/rsif.2012.0892.
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Dr. Cara Gormally, a teaching faculty member in the School of Biology, along with research collaborators Peggy Brickman and Mary Lutz at the University of Georgia, have developed the Test of Scientific Literacy Skills (TOSLS)--a freely available, psychometrically sound, multiple-choice instrument to measure college students’ scientific literacy skill development. The research and development of the TOSLS is described in the journal CBE Life Sciences Education (http://www.lifescied.org/content/11/4/364.full) and has recently been highlighted as an Editor’s Choice article in the journal Science (see below).
From Science January 18, 2013:
Editors Choice – EDUCATION
Scientific literacy, a skill needed beyond the classroom, is being integrated into general education curriculums, resulting in a need to assess students as they develop scientific literacy skills. Gormally et al. describe the development of the Test of Scientific Literacy Skills (TOSLS) as a freely available, time-efficient, and psychometrically sound test for use in undergraduate introductory science courses. Using definitions of scientific literacy in education policy documents and survey results from general education faculty, the team identified two major skill categories as measurable outcomes, or TOSLS skills: recognizing and analyzing the use of methods of inquiry, and organizing, analyzing, and interpreting quantitative data. An extensive pilot study that included testing students in a general biology course, individual student interviews, and several rounds of expert faculty evaluation suggested that the TOSLS is able to identify students' scientific literacy skill proficiency. Additionally, the TOSLS was sensitive enough to detect pre- to post-semester learning gains, suggesting that it will be valuable in future assessment efforts. The full list of editor’s choice articles can be found at (http://www.sciencemag.org/content/339/6117/twil.full#compilation-1-4-art...).
In what is believed to be the first study of its kind, researchers used genomic techniques to document the presence of significant numbers of living microorganisms – principally bacteria – in the middle and upper troposphere, that section of the atmosphere approximately four to six miles above the Earth’s surface.
Whether the microorganisms routinely inhabit this portion of the atmosphere – perhaps living on carbon compounds also found there – or whether they were simply lofted there from the Earth’s surface isn’t yet known. The finding is of interest to atmospheric scientists, because the microorganisms could play a role in forming ice that may impact weather and climate. Long-distance transport of the bacteria could also be of interest for disease transmission models.
The microorganisms were documented in air samples taken as part of NASA’s Genesis and Rapid Intensification Processes (GRIP) program to study low- and high-altitude air masses associated with tropical storms. The sampling was done from a DC-8 aircraft over both land and ocean, including the Caribbean Sea and portions of the Atlantic Ocean. The sampling took place before, during and after two major tropical hurricanes – Earl and Karl – in 2010.
The research, which has been supported by NASA and the National Science Foundation, was published online January 28th by the journal Proceedings of the National Academy of Sciences.
“We did not expect to find so many microorganisms in the troposphere, which is considered a difficult environment for life,” said Kostas Konstantinidis, an assistant professor in the School of Civil and Environmental Engineering at the Georgia Institute of Technology. “There seems to be quite a diversity of species, but not all bacteria make it into the upper troposphere.”
Aboard the aircraft, a filter system designed by the research team collected particles – including the microorganisms – from outside air entering the aircraft’s sampling probes. The filters were analyzed using genomic techniques including polymerase chain reaction (PCR) and gene sequencing, which allowed the researchers to detect the microorganisms and estimate their quantities without using conventional cell-culture techniques.
When the air masses studied originated over the ocean, the sampling found mostly marine bacteria. Air masses that originated over land had mostly terrestrial bacteria. The researchers also saw strong evidence that the hurricanes had a significant impact on the distribution and dynamics of microorganism populations.
The study showed that viable bacterial cells represented, on average, around 20 percent of the total particles detected in the size range of 0.25 to 1 microns in diameter. By at least one order of magnitude, bacteria outnumbered fungi in the samples, and the researchers detected 17 different bacteria taxa – including some that are capable of metabolizing the carbon compounds that are ubiquitous in the atmosphere – such as oxalic acid.
The microorganisms could have an impact on cloud formation by supplementing (or replacing) the abiotic particles that normally serve as nuclei for forming ice crystals, said Athanasios Nenes, a professor in the Georgia Tech School of Earth and Atmospheric Sciences and School of Chemical and Biomolecular Engineering.
“In the absence of dust or other materials that could provide a good nucleus for ice formation, just having a small number of these microorganisms around could facilitate the formation of ice at these altitudes and attract surrounding moisture,” Nenes said. “If they are the right size for forming ice, they could affect the clouds around them.”
The microorganisms likely reach the troposphere through the same processes that launch dust and sea salt skyward. “When sea spray is generated, it can carry bacteria because there are a lot of bacteria and organic materials on the surface of the ocean,” Nenes said.
The research brought together microbiologists, atmospheric modelers and environmental researchers using the latest technologies for studying DNA. For the future, the researchers would like to know if certain types of bacteria are more suited than others for surviving at these altitudes. The researchers also want to understand the role played by the microorganisms – and determine whether or not they are carrying on metabolic functions in the troposphere.
“For these organisms, perhaps, the conditions may not be that harsh,” said Konstantinidis. “I wouldn’t be surprised if there is active life and growth in clouds, but this is something we cannot say for sure now.”
Other researchers have gathered biological samples from atop mountains or from snow samples, but gathering biological material from a jet aircraft required a novel experimental setup. The researchers also had to optimize protocols for extracting DNA from levels of biomass far lower than what they typically study in soils or lakes.
“We have demonstrated that our technique works, and that we can get some interesting information,” Nenes said. “A big fraction of the atmospheric particles that traditionally would have been expected to be dust or sea salt may actually be bacteria. At this point we are just seeing what’s up there, so this is just the beginning of what we hope to do.”
The Georgia Tech team also included Natasha DeLeon-Rodriguez and Luis-Miguel Rodriguez-R from the Georgia Tech School of Biology, Terry Lathem from the Georgia Tech School of Earth and Atmospheric Sciences, and James Barazesh and Michael Bergin from the Georgia Tech School of Civil and Environmental Engineering. The Georgia Tech team received assistance from researchers Bruce Anderson, Andreas Beyersdorf, and Luke Ziemba with the Chemistry and Dynamics Branch/Science Directorate at the NASA Langley Research Center in Hampton, Va.
CITATION: Natasha DeLeon-Rodriguez, et al., “Microbiome of the upper troposphere: Species composition and prevalence, effects of tropical storms, and atmospheric implications,” Proceedings of the National Academy of Sciences (2013): www.pnas.org/cgi/doi/10.1073/pnas.1212089110
This research was supported, in part, by NASA grant number NNX10AM63G, by a GAANN Fellowship from the U.S. Department of Education, a NASA-NESSF fellowship, and by a National Science Foundation (NSF) graduate research fellowship. The opinions expressed are those of the authors and do not necessarily represent the official views of NASA, the Department of Education or the NSF.
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Sand-dwelling and rock-dwelling cichlids living in East Africa’s Lake Malawi share a nearly identical genome, but have very different personalities. The territorial rock-dwellers live in communities where social interactions are important, while the sand-dwellers are itinerant and less aggressive.
Those behavioral differences likely arise from a complex region of the brain known as the telencephalon, which governs communication, emotion, movement and memory in vertebrates – including humans, where a major portion of the telencephalon is known as the cerebral cortex. A study published this week in the journal Nature Communications shows how the strength and timing of competing molecular signals during brain development has generated natural and presumably adaptive differences in the telencephalon much earlier than scientists had previously believed.
In the study, researchers first identified key differences in gene expression between rock- and sand-dweller brains during development, and then used small molecules to manipulate developmental pathways to mimic natural diversity.
“We have shown that the evolutionary changes in the brains of these fishes occur really early in development,” said Todd Streelman, an associate professor in the School of Biology and the Petit Institute for Bioengineering and Biosciences at the Georgia Institute of Technology. “It’s generally been thought that early development of the brain must be strongly buffered against change. Our data suggest that rock-dweller brains differ from sand-dweller brains – before there is a brain.”
For humans, the research could lead scientists to look for subtle changes in brain structures earlier in the development process. This could provide a better understanding of how disorders such as autism and schizophrenia could arise during very early brain development.
The research was supported by the National Science Foundation and published online April 23 by the journal.
“We want to understand how the telencephalon evolves by looking at genetics and developmental pathways in closely-related species from natural populations,” said Jonathan Sylvester, a postdoctoral researcher in the Georgia Tech School of Biology and lead author of the paper. “Adult cichlids have a tremendous amount of variation within the telencephalon, and we investigated the timing and cause of these differences. Unlike many previous studies in laboratory model organisms that focus on large, qualitative effects from knocking out single genes, we demonstrated that brain diversity evolves through quantitative tuning of multiple pathways.”
In examining the fish from embryos to adulthood, the researchers found that the mbuna, or rock-dwellers, tended to exhibit a larger ventral portion of the telencephalon, called the subpallium – while the sand-dwellers tended to have a larger version of the dorsal structure known as the pallium. These structures seem to have evolved differently over time to meet the behavioral and ecological needs of the fishes. The team showed that early variation in the activity of developmental signals expressed as complementary dorsal-ventral gradients, known technically as “Wingless” and “Hedgehog,” are involved in creating those differences during the neural plate stage, as a single sheet of neural tissue folds to form the neural tube.
To specifically manipulate those two pathways, Sylvester removed clutches of between 20 and 40 eggs from brooding female cichlids, which normally incubate fertilized eggs in their mouths. At about 36 to 48 hours after fertilization, groups of eggs were exposed to small-molecule chemicals that either strengthened or weakened the Hedgehog signal, or strengthened or weakened the Wingless signal. The chemical treatment came while the structures that would become the brain were little more than a sheet of cells. After treatment, water containing the chemicals was replaced with fresh water, and the embryos were allowed to continue their development.
“We were able to artificially manipulate these pathways in a way that we think evolution might have worked to shift the process of rock-dweller telencephalon development to sand-dweller development, and vice-versa. Treatment with small molecules allows us incredible temporal and dose precision in manipulating natural development,” Sylvester explained. “We then followed the development of the embryos until we were able to measure the anatomical structures – the size of the pallium and subpallium – to see that we had transformed one to the other.”
The two different brain regions, the dorsal pallium and ventral subpallium, give rise to excitatory and inhibitory neurons in the forebrain. Altering the relative sizes of these regions might change the balance between these neuronal types, ultimately producing behavioral changes in the adult fish.
“Evolution has fine-tuned some of these developmental mechanisms to produce diversity,” Streelman said. “In this study, we have figured out which ones.”
The researchers studied six different species of East African cichlids, and also worked with collaborators at King’s College in London to apply similar techniques in the zebrafish.
As a next step, the researchers would like to follow the embryos through to adulthood to see if the changes seen in embryonic and juvenile brain structures actually do change behavior of adults. It’s possible, said Streelman, that later developmental events could compensate for the early differences.
The results could be of interest to scientists investigating human neurological disorders that result from an imbalance between excitatory and inhibitory neurons. Those disorders include autism and schizophrenia. “We think it is particularly interesting that there may be some adaptive variation in the natural proportions of excitatory versus inhibitory neurons in the species we study, correlated with their natural behavioral differences,” said Streelman.
In addition to the researchers already mentioned, the study included undergraduate coauthors Constance Rich and Chuyong Yi from Georgia Tech, and Joao Peres and Corinne Houart from King’s College in London. Rich is presently in the neuroscience PhD program at the University of Cambridge.
This research was supported by the National Science Foundation (NSF) under grants IOS 0922964 and IOS 1146275. The findings and conclusions are those of the authors and do not necessarily represent the official views of the NSF.
CITATION: Sylvester, J.B., et al., “Competing Signals Drive Telencephalon Diversity,” (Nature Communications, 2013).
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Writer: John Toon
Ryan Bloomquist, the School of Biology’s first joint doctoral DMD/PhD student has received a F30 Ruth L. Kirschstein National Research Service Award (NRSA) aimed at investigating the process of dental tissue regeneration. The F30 Ruth L. Kirschstein NRSA is awarded to promising applicants with the potential to become productive, independent and highly trained physician-scientists.
Regenerative medicine, the general process of replacing or regenerating human cells and tissues to restore normal function, is emerging as a promising therapeutic strategy to address a wide array of congenital, traumatic and infectious diseases. On the forefront of these strategies is the field of regenerative dentistry, whereby cells or cell scaffolds are transplanted into oral tissues with the aim of culturing new teeth to restore ideal dental function and aesthetic. Although regenerative dentistry has been studied for many years, relatively little is known about how we naturally replace our teeth, including the identity of developmental precursor cells that give rise to new teeth.
Under the direction of Associate Professor Todd Streelman, Bloomquist seeks to exploit the continuously replaced dentition of the Lake Malawi cichlid fish to reveal the cells responsible for vertebrate tooth regeneration. Much like sharks and many other vertebrates, Lake Malawi cichlid fish from East Africa continuously replace their teeth throughout their lifetimes – making them ideal for studying dental regeneration. Beyond its direct application to regenerative dentistry, Bloomquist and Streelman hope to gain further insight on the general process of tissue regeneration that may contribute key insights for regenerative biology and engineering.
Bloomquist is completing a doctorate in Dental Medicine (DMD) at Georgia Regents University School of Dentistry and a PhD in Biology at Georgia Tech. He is the first student in either university to receive the prestigious F30 Ruth L. Kirschstein fellowship.