“Since we launched in 2012, the core has evolved quite a bit,” says Dalia Arafat-Gulick, who manages the lab of Petit Institute researcher Greg Gibson (professor in the School of Biological Sciences) and the Genome Analysis Core (contained within the Gibson lab space), in the Krone Engineered Biosystems Building. “The usage and diversity of equipment has definitely increased since then, and so have the services we provide.”

It all started with the Fluidigm Biomark quantitative real-time PCR (polymerase chain reaction). PCR, sometimes called “molecular photocopying,” is a fast technique to amplify small segments of DNA. The PCR technique was invented more than 30 years ago and it has transformed the study of DNA – mapping in the Human Genome Project.

PCR can be inexpensive if you’re only looking at a few genes, according to Gibson. “The costs can add up quickly,” he says. “But the Fluidigm platform brings the costs down further.”

This makes it possible, for example, to monitor the expression of 96 genes in 96 samples for around $1,000 (or 10 cents per reaction), “with high accuracy,” Gibson adds.

The latest transformative tool in Georgia Tech’s Genome Analysis Core is the ddSEQ, part of the single-cell sequencing system co-developed by Illumina and Bio-Rad. The Marcus Foundation collaborated with the Petit Institute in providing funding support, as Georgia Tech last April became the first research institution in the Southeast to deploy the ddSEQ.

“The ddSEQ is essentially a sample preparation platform,” explains Steve Woodard, director of core facilities for the Petit Institute. “You’re preparing samples to go downstream for sequencing in the Molecular Evolution Core or the High-Throughput DNA Sequencing Core. Just another example of how our core facilities are integrated.”

The process typically begins upstream in the Cellular Analysis and Cytometry Core, where researchers will utilize flow cytometry to isolate specific cell populations. Then the ddSEQ separates those cells into a sub-nanoliter oil based droplets on a disposable cartridge, in under five minutes, “which gives you a fast turnaround for each cell captured,” Arafat-Gulick says.

Each cartridge can accommodate up to four samples, which allows each sample to be processed simultaneously. Cell lysis, reverse transcription, and bar-coding occur inside the individual droplets, which allow researchers to amplify several thousand transcripts in each cell.

“The next step is to actually get them sequenced,” Arafat-Gulick says. “That’s where the downstream cores [High Throughput and Molecular Evolution] come in. They have the equipment that allows us to ultimately analyze the gene expression levels of these cells.” 

In this way, researchers can peek inside hundreds – or even thousands – of cells, seeing how much diversity in the mixture there is, or monitoring how individual cells are responding to treatments, all for around $10 a cell. The technology also exists to sequence the DNA, and measure methylation states of genes, “which is transforming genomic analysis,” Gibson says.

“The next step is to actually get them sequenced,” Arafat-Gulick says. “That’s where the downstream cores [High Throughput and Molecular Evolution] come in. They have the equipment that allows us to ultimately analyze the gene expression levels of these cells.”

A number of Petit Institute researchers, including Krish Roy, Ed Botchwey, and Gibson, are working in the single-cell arena now, utilizing the equipment, techniques, and services available through the Genome Analysis Core.

“It’s a quantitative way to look at RNA sequencing on a single cellular level,” Arafat-Gulick says. “Principal investigators really want to see what’s happening on a cell to cell basis, and this new technology makes this accessible, at a much faster rate than before.”

•••

The Petit Institute's state-of-the-art research facilities, known as "Core Facilities," serve as a shared resource for the bioengineering and bioscience community. Consultation, training, and technical support is available for a variety of research projects. Users have access to over 100 pieces of lab equipment totaling over $24 million. 

Learn more about the Petit Institute’s core facilities and how they can support your research projects. 

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

The researchers aim to identify metabolic features in head and neck cancers that are predictive of tumor response to a new chemotherapeutic drug, ß-lapachone, currently in clinical trial at the University of Texas-Southwestern (UTSW). Fellow leaders of the project are David Boothman, Ph.D., from the UTSW Medical Center and Cristina Furdui, Ph.D., from the Wake Forest School of Medicine.

Joshua Lewis, an Emory M.D./BME Bioinformatics Ph.D. student in Kemp’s lab, developed a genome-wide model of metabolism in head and neck cancer that explained why the cytotoxicity to ß-lapachone differed between radiation-sensitive and radiation-resistant cancer cells.

The research team identified new molecular targets for enhancing cell death with the drug—validating the results with a 332 gene RNAi screen. The modeling analysis suggests that the radiation-resistant cells rerouted metabolism and altered the enzymatic cycling of ß-lapachone, rendering them more susceptible to the chemotherapy.

“I’ve learned through this project how devastating head and neck cancer (HNC) is for patients, and the incidence of HNC is particularly high here in the Southeast compared to the rest of the US,” said Kemp, a researcher with the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

“There are very few FDA-approved drugs for HNC and the survival rate for the late-stage cancer patients we are examining has been relatively stagnant for the past three decades," Kemp added. “Our goals are to develop computational models that factor in patient-to-patient variability in HNC metabolism and use these tools to predict who will respond well to the new ß-lapachone therapies.”

Head and neck cancers include cancers of the larynx (voice box), throat, lips, mouth, nose, and salivary glands.

As part of the award, the researchers will join and participate in the NCI Cancer Systems Biology Consortium. The multidisciplinary Cancer Systems Biology Consortium, funded by the National Cancer Institute, aims to tackle the most perplexing issues in cancer to increase our understanding of tumor biology, treatment options, and patient outcomes.

Media Contact:

Walter Rich
Communications Manager
Wallace H. Coulter Department of Biomedical Engineering

Overall, the news from the study is good. Evolution appears, through the ages, to have weeded out genetic influences that promote disease, while promulgating influences that protect from disease. But there's also a hint of bad news for us modern folks. That generally healthy trend might have reversed in the last 500 to 1,000 years. 

So, who appears to have had the healthier genes? The “cavemen?” We moderns? And who was more genetically susceptible to mental illness?

READ about our genomic health heritage here, and meet our Copper Age ancestor, the “Iceman.”

“We were testing an intuition,” says Urko Marigorta, lead author of the study, “Transcriptional Risk Scores link GWAS to eQTL and Predict Complications in Crohn’s Disease,” published in the journal Nature Genetics.

“We wanted to see if checking the actual expression of pathogenic genes involved in disease is better than just looking at an individual’s DNA when assessing the risk for disease,” adds Marigorta, a postdoctoral researcher in lab of Greg Gibson, professor in the School of Biological Sciences and a researcher in the Petit Institute for Bioengineering and Bioscience at Georgia Tech.

This was part of a multicenter research initiative, the Crohn’s & Colitis Foundation’s “RISK Stratification” study (the largest new-onset study of pediatric Crohn’s disease patients), and a follow-up to research published earlier this year in the journal, The Lancet.

That study, says Gibson, evaluated “whether anti-TNF treatment really is beneficial in reducing inflammation and preventing progression to complicated Crohn’s disease. It is, but apparently only for a subset of patients. Our contribution there was to show that this subset can, to some extent, be identified at diagnosis on the basis of their overall gene expression profile in the ileum.”

The Nature Genetics paper takes advantage of the data sets analyzed in the previously published research. The RISK Stratification Study involved 28 clinics and 1,800 pediatric patients – a good sample size, according to Marigorta, who adds, “most important, [we had] two forms of biological data: DNA and gene expression from the small intestine. Importantly, the gene expression from RISK was obtained at diagnosis, when kids went to the hospital and before developing complicated versions of Crohn’s disease.”

So basically, Marigorta and Gibson wanted to test their novel approach, TRS, against genetic risk scores (GRS), or scores based on an individual’s DNA, which is currently the dominant approach in the field. But predicting disease risk from just DNA is difficult.

“In the last few years we’ve learned about many genes that are associated with disease – genes that have mutations, that are more frequent in people with disease than in healthy people,” Marigorta says. “But many people with mutated genes do fine, whereas others without them end up getting sick with some disease. Most of the field is trying to discover more of these mutations, which is totally fine because that will tell us more about biology, and will make for good drug targets. But we’re not sure it will add that much in terms of prediction.”

Marigorta’s statistical and bioinformatics analyses of the genomic data demonstrated that their intuition was on target: gauging the expression of risk genes (TRS) does a better job of predicting complications of Crohn’s than just adding up the number of risk genes (GRS).

“So, instead of trying to predict how good a football team is going to be by adding up how many players make $10 million a year, we actually evaluate how well they are performing,” says Gibson, using a familiar sports analogy.

This paper published in Nature Genetics was a collaboration of 23 author/researchers from 18 institutions – two in Canada and 16 in the U.S., including Emory University’s School of Medicine. Emory physician/professor Subra Kugathasan, director of the Children’s Healthcare of Atlanta Combined Center for Pediatric Inflammatory Bowel Disease, shares senior authorship with Gibson (who was the corresponding author). Key leadership also came from co-authors Lee Denson (Cincinnati Children’s Hospital) and Jeff Hyams (Connecticut Children’s Medical Center)

Going forward, Marigorta sees two primary directions that the TRS research may take.

“We’d like to see if it works for other traits and we have evidence that it does, at least for autoimmune diseases such as juvenile arthritis,” he says. “And more importantly, we’d like to see if it works when using gene expression from blood draws. Imagine, down the road, if you could fine-tune the predictions of risk due to your DNA with information gained from looking at gene expression from a simple blood draw at your once-a-year checkup.”

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

Mitochondrial replacement (MR) therapy combines the nuclear DNA from the mother with healthy mitochondria from a donor egg to create a healthy new egg that can be fertilized with the father’s sperm, thereby yielding a “three-person baby.” Last year, the world’s first three-person baby resulting from this method was delivered by U.S. doctors in Mexico, where there are no laws prohibiting the procedure.

The healthy newborn got about 0.1 percent of his DNA from the donor, and the vast majority of his genetic code – specifying eye color, hair, etc. – from his mom and dad.

Mitochondrial DNA comprises just a small percentage of our total DNA, containing just 37 of the 20,000 to 25,000 protein-coding genes in our body. And while nuclear DNA comes from both parents, “our mitochondrial DNA comes directly from our mothers, so my mitochondrial genome will be exactly like my mother’s, yours will be like your mother’s, and so on,” says Lavanya Rishishwar, former grad student in the lab of Petit Institute researcher King Jordan and team lead for Applied Bioinformatics Laboratory (ABiL, a public-private partnership between Georgia Tech and IHRC Inc.).

While the method hasn’t been green lighted in the U.S. yet, the United Kingdom gave the go-ahead for MR therapy in December. This announcement came in the wake of concerns about the safety of MR therapy that were raised by evolutionary biologists, who argue that nuclear and mitochondrial genomes evolved concurrently, and therefore mitochondria from one person or population may not be compatible with nuclear material from another.

In support of the evolutionary biologists’ nuclear-mitochondrial mismatch hypothesis, a number of previous studies on model organisms have provided evidence for incompatibility between nuclear and mitochondrial genomes from divergent populations of the same species. But a recent study by Jordan and Rishishwar published in BMC Genomics lays those fears to rest.

“The alarm was raised based on work that was done on model systems,” says Jordan, associate professor in the School of Biological Sciences and director of the Bioinformatics Graduate Program. “They didn’t work with humans, they worked with fruit flies, with mice, and those experiments resulted in a host of different problems for the resulting offspring. The key is, those were artificial experiments. Meanwhile, there’s been an ongoing natural experiment that has been conducted over millennia in human populations.”

So Jordan and Rishishwar tested the nuclear-mitochondrial mismatch hypothesis for humans by observing the source: humanity. They used data from the 1,000 Genomes Project and the Human Genome Diversity Project, studying the incidents of nuclear- mitochondrial DNA mismatch seen in more than 3,500 people from about 60 populations on five continents.

“We’ve been working for some years on human population genomics and remain interested in admixed American populations,” Jordan says. “The trajectory of modern human evolution for the past 50,000 to 100,000 years starts with the journey out of Africa, followed by a long period when populations were geographically isolated for the most part.  During that time, human populations genetically diverged since they were physically isolated.”

But over the past 500 years or so, since Columbus came to the new world from Europe, “that process of isolation and divergence got flipped upside down,” Jordan notes. “Over a very short evolutionary time, you had populations from the Americas, Europe, and shortly thereafter, Africa because of the transatlantic slave trade, that were all brought together.”

Hence, in the Americas we’ve seen the creation of genome sequences that are evolutionarily novel in the history of humanity, in that they contain combinations of variants that had never existed together before. Jordan and his team have been studying this for a while, and understood that healthy individuals can bear combinations of variants that had different ancestral sources within the same genomic background.

“We knew that at a very intuitive level because of our own research,” says Jordan, who stumbled on a paper in Nature expressing the grave concerns of evolutionary biologists and thought, “instead of relying on artificial experiment systems, why don’t we just try to read the results of this long, ongoing experiment of human evolution and see what it tells us.”

They found that even people with very similar nuclear DNA (nDNA) genomes can have highly divergent mitochondrial DNA (mtDNA) and vice versa. Ultimately, their results showed that mitochondrial and nuclear genomes from divergent human populations can co-exist in healthy individuals, indicating that mismatched nDNA-mtDNA combinations are basically harmless and not likely to jeopardize the safety of MR therapy.

“We tend to think that the story of our evolution is the story of migration, physical isolation, and genetic diversification,” Jordan says. “But all throughout that process, there was admixture along the way. It’s not like there was a linear, onward march. It confirms and underscores the fact that humans are a relatively evolutionarily young species, and from the genetic perspective, there is complete compatibility between human populations.”

Men of African descent suffer disproportionately from prostate cancer compared to men of other ethnicities. So, researchers from 11 institutions in the U.S. and Africa will look at genetic susceptibility and population genomics of prostate cancer in men of African descent. 

Specifically, the study hopes to provide new information about the genetic etiology of prostate cancer and evaluate how population differences and history of African and African American populations affects the underlying reasons for high rates of prostate cancer in African Americans. 

Lachance, a Petit Institute faculty member, and his lab will use their expertise in population genetics and computational biology to focus on the evolutionary genomics of prostate cancer in African populations. 

“It is important to know which populations and ancestries have a genetic predisposition to prostate cancer and to understand whether these health disparities are due to natural selection or neutral evolution,” said Lachance.

The five-year study, funded by the National Cancer Institute, is led by principal investigator Timothy Rebbeck, professor of medical oncology at the Dana-Farber Cancer Institute and professor of cancer epidemiology at the Harvard T.H. Chan School of Public Health.

“Aggressive prostate cancer is the form of the disease that is the most important to control,” said Rebbeck. “African descent men, including African Americans, seem to have biologically more aggressive forms of prostate cancer than other groups.  By studying African descent men, we may also learn about aggressive prostate cancer so that we can better prevent and treat the disease.”

The participating centers, part of an international consortium called Men of African Descent and Carcinoma of the Prostate, include: Dana-Farber Cancer Institute (Boston); 37 Military Hospital (Ghana); Albert Einstein College of Medicine (New York); the Center for Proteomic & Genomic Research and Clinical Laboratory Services (South Africa); Hȏpital Général de Grand Yoff (Senegal);  Korle-Bu Hospital (Ghana); National Health Laboratory Services (South Africa); Stellenbosch University (South Africa); University College Hospital (Nigeria); as well as the National Institutes of Health/National Cancer Institute, the Stanford Cancer Institute, and Georgia Tech.

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

But what about all of the other cases?

A study from School of Biology Professor Greg Gibson’s group at the Georgia Institute of Technology, recently published in the American Journal of Human Genetics, argues that we should be looking not just at the structural parts of genes, but also the regulatory regions around them.  

The paper, entitled “A Burden of Rare Variants Associated with Extremes of Gene Expression in Human Peripheral Blood,” demonstrates that there is a burden of rare genetic variants in these regions that associates with abnormal gene expression.  It does not show that they cause birth defects, but does suggest that they need to be seriously considered as WGS technology develops.

Gibson explains it in the form of a metaphor about building a house.  

“There are two critical components, the bricks and mortar, and the plans for where to put them,” says Gibson, a faculty member of the Petit Institute for Bioengineering and Bioscience. “If there is a defect in the glass or a crack in a piece of wood, then sooner or later the structure may fall apart. This is what current approaches focus on, the so-called protein coding-regions. But if the architect’s plans call for more windows than the beams can support, or the contractor doesn’t deliver enough concrete, then the consequences can be just as bad.”  

We now know that a lot more of the genetic component related to differences in the way we look and behave (or what makes us susceptible to different diseases) is in the planning than the structural components. This insight is based on studies of common polymorphisms, namely the millions of genetic differences that we all share. The new study argues that it will also be true of rare genetic variants, including new mutations that are specific to a single person.

Graduate student Jing Zhao sequenced the regulatory regions of almost 500 genes from 500 participants in the Georgia Tech-Emory Predictive Health Institute study, and added up the number of rare mutations in people whose expression of those genes was toward the extreme.  The result is what she calls a “smile plot,” because the curve has a high number at either end and low number in the middle. It means that the plans can be off in either direction, making too little or too much transcript for each gene.  

“It is as if all the houses with crooked window frames are that way not because of the wood quality, but because each builder made different mistakes when putting the frames in,” Gibson says. 

Furthermore, Gibson says, there seem to be specific subsets of genes where these events are more or less likely to happen. This is important, because it implies that we may be able to develop algorithms that identify the most likely places for regulation to go wrong, based on the evolutionary conservation of different parts of genes.

Projects such as President Obama’s precision medicine initiative aim to use genomics to help researchers decipher individual causes of disease.  In the next few years, Gibson expects that much larger datasets of tens and eventually hundreds of thousands of people, in many different tissues, will appear.  

“The challenges,” Gibson says, “are as much in the bioinformatics than the technology. “

In addition to Gibson and Zhao, also contributing to the published study were research scientist Dalia Arafat-Gulick (lab manager for the Gibson lab), T.J. Cradick (former director of the Protein Engineering Facility at Georgia Tech, now head of genome editing for CRISPR Therapeutics in Cambridge, Massachusetts), Cirian Lee (former postdoc at Georgia Tech, now at Rice University), Urko Marigorta (postdoc in the School of Biology), Gang Bao (former Georgia Tech professor, now at Rice University), Idowu Akinsanmi (former researcher in Bao’s lab at Georgia Tech) and Samridhi Banskota, an undergraduate student in the Gibson lab.

Read the study here.

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

“We’re rebooting,” says CIG Director Greg Gibson, professor in the Georgia Institute of Technology’s School of Biology and faculty member of the Parker H. Petit Institute for Bioengineering and Bioscience. “We’ve got critical mass now, so the time is right for a reboot.”

Gibson is kind of like a head football coach rebuilding his game plan around a new combination of talented core personnel. But instead of a multi-threat quarterback, nimble wide receivers and tenacious offensive linemen, CIG is counting on a diverse team of biologists, engineers and other researchers to carry out work that can impact the future of medicine.

“Over the past several years we’ve attracted about half a dozen people who have expertise in quantitative genetics and analysis of human genomes, and that’s in addition to another half a dozen who were already here,” says Gibson.

The CIG team is comprised mostly of faculty from the School of Biology, including Gibson, King Jordan, Joe LaChance, Annalise Paaby, Todd Streelman, Fred Vannberg and Soojin Yi. CIG’s other faculty members are Melissa Kemp, Peng Qiu, Eberhard Voit and May Wang from the Wallace H. Coulter Department of Biomedical Engineering.

Gibson’s research collaborators include the Predictive Health Institute and multiple pediatric autoimmune disease experts at Emory University, the Georgia Tech Center for Computational Health (headed by Jimeng Sun and Jim Rehg in the School of Computational Science and Engineering) and Bruce Weir's statistical genetics team at the University of Washington.  Other CIG investigators similarly engaged in dozens of national and international collaborators are expanding the reach of the Center.

They bring a wide-range of interest areas and skill sets to the CIG mix, including but not limited to bioinformatics, machine learning, single cell imaging, computational modeling, the evolution of behavior, infectious disease, human population genetics, cardiovascular disease, electronic medical records, and cryptic genetic variation, or CGV, which refers to unexpressed, bottled-up genetic potential that can fuel evolution – nature’s curveball, served up under abnormal conditions, and a concept that interests researchers like Gibson and Paaby, for example.

“It’s not a theme you find commonly in human genetics right now,” says Gibson. “But it’s something we feel is a very important part of personalized medicine.”

Gibson figures that the CIG’s multi-disciplined team of pioneering scientists and engineers will also serve as an excellent recruiting tool – to attract graduate students, as well as future grant opportunities.

“We have a strong nucleus to carry out the real objective of the center, which is to provide a genetics focus for the systems biology and genomics initiatives on campus. It’s pretty much what I envisaged when I first got here,” says Gibson, who came to Georgia Tech in 2009 following a professorial fellowship at University of Queensland in his native Australia.

“Genetics is a big part of contemporary biology,” he adds. “And if we’re looking ahead, it’s a big part of anything to do with predictive health and personalized medicine.”

Center for Integrative Genomics

CONTACT:

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience

Working with hundreds of these colorful fish, researchers are beginning to understanding how the animals maintain their hundreds of teeth throughout their adult lives. By studying how structures in embryonic fish differentiate into either teeth or taste buds, the researchers hope to one day be able to turn on the tooth regeneration mechanism in humans – which, like other mammals, get only two sets of teeth to last a lifetime.

The work, which also involved a study of dental differentiation in mice, shows that the structures responsible for growing new teeth may remain active for longer than previously thought, suggesting that the process might be activated in human adults.

The research was conducted by scientists from the Georgia Institute of Technology in Atlanta and King’s College in London, and published October 19 in early edition of the journal Proceedings of the National Academy of Sciences. The research was supported by the National Institute of Dental and Craniofacial Research, part of the U.S. National Institutes of Health.

“We have uncovered developmental plasticity between teeth and taste buds, and we are trying to understand the pathways that mediate the fate of cells toward either dental or sensory development,” said Todd Streelman, a professor in the Georgia Tech School of Biology. “The potential applications to humans makes this interesting to everybody who has dealt with dental issues at one time or another in their lives.”

Worldwide, approximately 30 percent of persons have lost all their teeth by the time they reach the age of 60. Beyond the painful dental health issues, this can causes significant medical and nutritional problems that can shorten life.

To understand more about the pathways that lead to the growth and development of teeth, Streelman and first author Ryan Bloomquist – a DMD/PhD student at Georgia Tech and Georgia Regents University – studied how teeth and taste buds grow from the same epithelial tissues in embryonic fish. Unlike humans, fish have no tongues, so their taste buds are mixed in with their teeth, sometimes in adjacent rows.

The Lake Malawi cichlids have adapted their teeth and taste buds to thrive in the unique conditions where they live. One species eats plankton and needs few teeth because it locates its food visually and swallows it whole. Another species lives on algae which must be scraped or snipped from rocky lake formations, requiring both many more teeth and more taste buds to distinguish food.

The researchers crossed the two closely-related species, and in the second generation of these hybrids, saw substantial variation in the numbers of teeth and taste buds. By studying the genetic differences in some 300 of these second-generation hybrids, they were able to tease out the genetic components of the variation.

“We were able to map the regions of the genome that control a positive correlation between the densities of each of these structures,” Streelman explained. “And through a collaboration with colleagues at King’s College in London, we were able to demonstrate that a few poorly studied genes were also involved in the development of teeth and taste buds in mice.”

By bathing embryonic fish in chemicals that influence the developmental pathways involved in tooth and taste bud formation, the researchers then manipulated the development of the two structures. In one case, they boosted the growth of taste buds at the expense of teeth. These changes were initiated just five or six days after the fish eggs were fertilized, at a stage when the fish had eyes and a brain – but were still developing jaws.

“There appear to be developmental switches that will shift the fate of the common epithelial cells to either dental or sensory structures,” Streelman said.

Though they have very different purposes and final anatomy, teeth and taste buds originate in the same kind of epithelial tissue in the developing jaws of embryonic fish. These tiny buds differentiate later, forming teeth with hard enamel – or soft taste buds.

“It’s not until later in the development of a tooth that it forms enamel and dentine,” said Streelman. “At the earliest stages of development, these structures are really very similar.”

The studies in fish and mice suggest the possibility that with the right signals, epithelial tissue in humans might also be able to regenerate new teeth.

“It was not previously thought that development would be so plastic for structures that are so different in adult fish,” Streelman said. “Ultimately, this suggests that the epithelium in a human’s mouth might be more plastic than we had previously thought. The direction our research is taking, at least in terms of human health implications, is to figure out how to coax the epithelium to form one type of structure or the other.”

But growing new teeth wouldn’t be enough, Streelman cautions. Researchers would also need to understand how nerves and blood vessels grow into teeth to make them viable.

"The exciting aspect of this research for understanding human tooth development and regeneration is being able to identify genes and genetic pathways that naturally direct continuous tooth and taste bud development in fish, and study these in mammals,” said Professor Paul Sharpe, a co-author from King’s College. “The more we understand the basic biology of natural processes, the more we can utilize this for developing the next generation of clinical therapeutics: in this case how to generate biological replacement teeth."

As a next step, Streelman and research technician Teresa Fowler are working to determine how far into adulthood the plasticity between teeth and taste buds extends, and what can trigger the change.

In addition to those already mentioned, the research included Nicholas Parnell and Kristine Phillips from Georgia Tech, and Tian Yu from King’s College.

This research is supported by the National Institute of Dental and Craniofacial Research, part of the U.S. National Institutes of Health, under grants 2R01DE019637 (to J.T.S.) and 5F30DE023013 (to R.F.B.). Any opinions or conclusions are those of the authors and may not necessarily represent the official views of the NIH.

CITATION: Ryan F. Bloomquist, et al., “Co-Evolutionary Patterning of Teeth and Taste Buds,” (Proceedings of the National Academy of Sciences, 2015). http://www.pnas.org/content/early/2015/10/15/1514298112

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

Scientists from engineering, biology, chemistry, and computing won’t discover new vaccines and medical devices — or advance what we know about diseases — by working on their own. The next biomedical breakthroughs to provide accessible health care for billions of people worldwide will come from the collaboration between different laboratories and disciplines.

That core belief led to the creation of the Engineered Biosystems Building (EBB), the newest building at the Georgia Institute of Technology. The site opened in May and a formal dedication ceremony was held today. 

EBB houses labs for research in chemical biology, cell and developmental biology, and systems biology. The building allows Georgia Tech to consolidate its biomedical research efforts in the prevention, diagnosis, and treatment of cancer, diabetes, heart disease, infections, and other life-threatening conditions.

President G.P. “Bud” Peterson said the building symbolizes what Georgia Tech is all about — collaboration and innovation.

“The EBB will drive innovation and have an undeniable impact on biomedical science and human health,” Peterson said. “EBB brings together some of the world’s finest researchers in a collaborative environment, and these collaborations will result in incredible breakthroughs.”

The building provides nearly 219,000 square feet of multidisciplinary research space and enhances the Institute’s partnerships with Emory University Hospital and with Children’s Healthcare of Atlanta.

“Together, we are changing the lives of children,” said Donna Hyland, president and CEO of Children’s Healthcare. “The space within this building helps bring our new Pediatric Technology Center to life and gives researchers another place to combine expertise in clinical care, research, and technology to solve problems that will help make kids better today and healthier tomorrow.”

The building is located on 10th Street, at the north end of the existing biotechnology complex. Other buildings in the complex include: the Parker H. Petit Institute for Bioengineering and Bioscience, the U.A. Whitaker Biomedical Engineering Building, the Ford Environmental Science and Technology Building, and the Molecular Science and Engineering Building.

More than 140 faculty and nearly 1,000 graduate students from 10 different academic units work in the labs and facilities there.

“EBB puts Georgia Tech at the forefront of biosciences and bioengineering research,” said M.G. Finn, professor and chair of the School of Chemistry and Biochemistry.

The building’s unique design allows Georgia Tech researchers to expand their work, he said.

EBB contains “research neighborhoods” designed around a specific focus or topic. These neighborhoods bring together scientists, engineers, and researchers from different disciplines around common themes or areas of interest. They share laboratories, offices, and common spaces.

Stairs alternate on various floors, encouraging people to move within the neighborhoods and throughout the building and interact with one another. Small and informal meeting areas are located near the stairwells, to further encourage researchers to talk with one another.

“We will help, influence, and support one another and bring new insights in a way that can’t happen if a building is restricted to a particular department or discipline,” Finn said.

“Ultimately we are all working to fight disease and save lives,” he said. “EBB is designed to foster the research to do just that.”

EBB is the largest building investment in Georgia Tech history. The $113 million building was made possible because of a partnership between the Institute, the Georgia Tech Foundation, and the State of Georgia, Peterson said.

State appropriations provided $64 million for the project. Georgia Tech provided $15 million in Institute funds, and private funding raised another $34 million in commitments pledged over five years.

EBB will help drive Georgia’s economy, Peterson said.

“It will foster economic development through the formation of startup enterprises, the creation of high-skilled, high-paying jobs, and the commercialization of new devices, drugs, and technologies,” Peterson said.

It’s important to examine the fundamental cell biology principles that govern this process, to reach a better understanding of developmental biology and engineering novel multicellular systems, but there are a number of challenges. 

Functional micro-tissues derived from pluripotent embryonic stem cell (ESC) aggregates provide novel platforms for experimentation, but clarifying the factors that direct emergent spatial phenotypic patterns remains a hurdle. Computational modeling offers a complementary approach and provides a wealth of spatiotemporal data, but quantitative analysis of simulations and comparison to the experimental data is difficult. 

Quantitative descriptions of spatial phenomena across multiple systems and scales would enable unprecedented comparisons of computational simulations with experimental systems and leverage the ability of computational methods to interrogate the mechanisms of multicellular biology. 

To address these challenges, a group of researchers from multiple disciplines at the Georgia Institute of Technology have developed an innovative, portable pattern recognition pipeline, the first of its kind.

“There is a lot of biological data available. To some extent, it’s all image data, whether we’re talking about confocal microscopy or two-dimensional images of cells. The field has made significant advances the last 10 or 15 years in terms of quantifying images, but there are still gaping holes in terms of quantifying spatial patterns and how those emerge in cells over time,” says Doug White, lead author of a research paper entitled, “Quantitative multivariate analysis of dynamic multicellular morphogenic trajectories,” published this summer in the journal Integrative Biology (a publication of the Royal Society of Chemistry).

White, a recent Ph.D. graduate from the Wallace H. Coulter Department of Biomedical Engineering, now manages a team using mathematical modeling approaches to understand the guiding principles behind cancer drug design, for Takeda Pharmaceuticals in Boston. The research paper is the result of work he began about three years ago. His Ph.D. was focused on understanding stem cell biology using computational modeling. 

“We set out to come up with a method that was portable across multiple system that anybody can use, but still powerful enough to extract meaningful data,” he says.

The pipeline permits entirely new forms of quantitative analysis based upon the fundamental interconnectivity of multicellular networks, which the research team believes could revolutionize the characterization of biologically complex spatiotemporal phenomena. And it’s the first network-based approach currently capable of using single cell information on spatial positioning and cellular states to classify tissue level pattern dynamics.

“The Petit Institute has instruments that measure different images with different resolutions,” says Melissa Kemp, associate professor in the Coulter Department, faculty member of the Petit Institute for Bioengineering and Bioscience, who co-authored the paper and was White’s co-advisor. “This pipeline allows us to take any of those images of multicellular structures and redefines the structure in terms of individual cells. Once you can define those individual entities within the image, you can create these network structures.”

Their innovation is their ability to take a plain image from a microscope and turn it into a network structure, much like LinkedIn or Facebook uses to study social connections. “We can then use newly defined features of those structures as they evolve over time to understand the underlying biology,” Kemp says.

The interdisciplinary team contributing to the research paper includes Petit Institute faculty members Hang Lu (professor and James R. Fair Faculty Fellow in the School of Chemical and Biomolecular Engineering) and Todd Streelman (professor and associate chair for graduate studies in the School of Biology), as well as White’s co-advisor Todd McDevitt, who left Georgia Tech last year to join the Gladstone Institute. Other co-authors were Jonathan Sylvester (postdoctoral fellow in the Streelman lab) and Thomas Levario (graduate student in the Lu lab). All, with the exception of McDevitt, are now based in the new Engineered Biosystems Building in the cell and developmental bioengineering neighborhood.

“We’re excited about how this could be used in other prediction-based studies,” Kemp says.

The nice thing about the technology is its portability across many imaging modalities, according to White, who adds, “The sky is the limit in terms of what this technology is capable of.”

CONTACT

Jerry Grillo
Communications Officer II
Parker H. Petit Institute for
Bioengineering and Bioscience