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21st Century CuresSoutheast ConferenceApplying Systems Biology to Biomedical Research

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It is a privilege to welcome you to the third 21st Century Cures: Southeast Conference.

The Southeast is disproportionately affected by chronic diseases and preventable deaths. According to the Centers for Disease Control and Prevention, compared to other regions in the United States, citizens in our region face a greater risk of Alzheimer’s disease, asthma, adult obesity, stroke, cardiovascular disease, and breast, lung, and colon cancer. Compounding the issue are prescription drug abuse in some areas and a lack of access to health care for many communities. The people of the Southeast desperately need new solutions to these growing health crises.

Fortunately, the 21st Century Cures Act creates a path forward to address some of the most pressing human health challenges of our time. By accelerating research on cancer, the brain, and precision medicine, the Act has the potential to produce transformative research that will positively affect the health of millions across the Southeast. In addition, attendees from the academic and federal research institutions represented here today have an opportunity to collaborate regionally to overcome these grand challenges.

The sessions you will attend today focus on the impact of the growing field of systems biology on biomedical research, specifically in the two areas represented in our conference tracks: Computational Modeling of Health, and Microbes and Health. The agenda features the work of prestigious scientists in these fields and provides opportunities to learn from leaders within the National Institutes of Health.

After this event, you will have greater knowledge and scientific insight into the health issues facing the people of our region and nation. I hope you will make connections with potential collaborators from institutions across the Southeast that will lead to shared knowledge, strategic partnerships, and innovative research that addresses the challenges in the 21st Century Cures Act.

Thank you for joining us.

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Robert Nobles

Interim Vice Chancellor for ResearchUniversity of Tennessee

Welcome Message

Agenda Summary

Track One: Computational Modeling of Health

Track Two: Microbes and Health

Speakers

Poster Session

Special Thanks

Table of Contents

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H o w a r d H . B a k e r J r . C e n t e r f o r P u b l i c P o l i c y

Welcome Remarks

Robert Nobles

Interim Vice Chancellor for ResearchUniversity of Tennessee

Check-in, Breakfast, and Networking

Keynote

The Importance of Mechanistic Models – Now More Than Ever!

Grace C.Y. Peng

Director of Mathematical Modeling, Simulation, and Analysis at the National Institute of Biomedical Imaging and Bioengineering and Chair of the Interagency Modeling and Analysis Group (IMAG)

Track One: Computational Modeling of Health

Track Two: Microbes and Health

Reception and Poster Session

8 : 0 0 – 8 : 3 0 A MRotunda

8 : 3 0 - 8 : 4 5 A MToyota Auditorium

8 : 4 5 - 9 : 3 0 A MToyota Auditorium

9 : 4 5 A M - 4 : 3 0 P M Toyota Auditorium

Room 207/208

4 : 3 0 – 6 : 3 0 P M Rotunda

Agenda Summary

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Systems Biology Approaches to Cancer Research

Shannon Hughes

Program Director in the Division of Cancer Biology at the National Cancer Institute

Bridging Gaps: Multiscale Modeling with “Tiny Data”

Belinda Akpa

Assistant Professor of Integrated Synthetic and Systems Biology at North Carolina State University

Big Data Approaches to Tackle Tiny Bugs: New Drugs, Better Vaccines, and Improved Diagnostics of Infectious Diseases by the NIAID Systems Biology Consortium

Liliana Brown

Program Officer in the Office of Genomics and Advanced Technologies (OGAT) at the National Institute for Allergy and Infectious Diseases

Modeling Epithelial Cell Migration with Transcriptome and 3D Genome Data

Tian Hong and Rachel Patton McCord

Assistant Professors in the Department of Biochemistry and Cellular and Molecular Biology at the University of Tennessee

Funding Opportunities for Quantitative Sciences within NIGMS

Veerasamy (Ravi) Ravichandran

Program Director in the Division of Biophysics, Biomedical Technology, and Computational Biology at the National Institute of General Medical Sciences

Data Science and the Fight Against Cancer: News from the Frontier

Eric A. Stahlberg

Director of Biomedical Informatics and Data Science at Frederick National Laboratory for Cancer Research

Lunch and Networking in the Rotunda

Computational Modeling of HealthToyota Auditorium

T R A C K O N E

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Lunch and Networking in the Rotunda

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Microbes and HealthRoom 207/208

T R A C K T W O

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Probiotics, Prebiotics, and the Gut Microbiome: A Case for Lactose Intolerance

Andrea Azcarate-Peril

Associate Professor of Medicine at the University of North Carolina School of Medicine

The Gut Microbiota and Health: A Focus on Linking Intestinal Dysbiosis and Human Disease

Mariana Xavier Byndloss

Assistant Professor of Pathology, Microbiology, and Immunology at Vanderbilt University Medical Center

NCI Programs and Opportunities Supporting Microbiome-Related Studies

Phil Daschner

Program Director in the Cancer Immunology, Hematology, and Etiology Branch at the National Cancer Institute

From Microbes to Genomes and Back

Mircea Podar

Distinguished Staff Scientist and Leader of the Systems Genetics Group in the Biosciences Division at Oak Ridge National Laboratory

Exploring Microbial Biomarkers to Diagnose Enigmatic Diseases

Melissa Cregger

Staff Scientist in the Biosciences Division at Oak Ridge National Laboratory

The Gut Microbiome and Host Metabolism: Hand vs. Puppet

Joseph F. Pierre

Assistant Professor in the Department of Pediatrics at the University of Tennessee Health Science Center

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Belinda Akpa, PhD

Belinda Akpa joined North Carolina State University (NCSU) in August 2015 as a Chancellor’s Faculty Excellence Program cluster hire in Synthetic and Systems Biology. Akpa, an assistant professor in the Department of Molecular Biomedical Sciences, develops mathematical models to connect molecular events to dynamic physiological outcomes. She uses numerical simulations to bridge length-scales in integrated computational and experimental investigations, with the aim of accelerating the translation of molecular and cellular level findings to medical applications. Her current interests lie broadly within the realm of quantitative systems physiology.

Akpa obtained her bachelor’s, master’s, and doctoral degrees in chemical engineering from the University of Cambridge. As a Cambridge Commonwealth Trust Scholar, she worked in Lynn Gladden’s laboratory developing magnetic resonance methodologies for the quantitative study of dynamic heterogeneous systems. Akpa joined NCSU after serving on the faculty in the Department of Chemical Engineering at the University of Illinois, Chicago, where she initiated an interdisciplinary research program in systems physiology. Her work has been published in chemistry, interface science, pharmaceutical, and clinical journals. She has also mentored graduate and undergraduate research students with academic backgrounds ranging from chemical engineering, mathematics, and biology to pharmacy and astronomy.

M. Andrea Azcarate-Peril is an associate professor of medicine in the Gastrointestinal Division of the School of Medicine at the University of North Carolina, Chapel Hill (UNC). She is also the founding and current director of the UNC Microbiome Core Facility, which provides research and technical support to investigators interested in addressing the roles of host-associated microbiota in health and disease.

Azcarate-Peril is a microbiologist by training and has extensive experience in the characterization of complex microbial populations and functional metagenomics using culture-dependent and culture-independent methods, including Next Generation Sequencing. Her research projects have focused on functional genomics of probiotics and gut microbiome modulation by prebiotics for over 20 years, resulting in over 60 peer-reviewed publications. Her current projects aim to define modulators of the gut microbiome capable of reversing dysbioses induced by age, diet, and nutritional behaviors. She is particularly interested in the development of application-directed probiotic strains to address and prevent gastrointestinal disorders.

Azcarate-Peril received a bachelor’s degree in genetics from the Universidad Nacional de Misiones and a doctoral degree in microbiology from the Universidad Nacional de Tucumán in Argentina.

M. Andrea Azcarate-Peril, PhD

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Liliana Brown, PhD Mariana Byndloss, DVM, PhD

Liliana Brown is a program officer in the Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) in the National Institutes of Health (NIH). She directs the NIAID Systems Biology for Infectious Diseases Consortium, which brings together scientists from the different fields of microbiology, immunology, infectious diseases medicine, the microbiome, physics, bioinformatics, computational biology, statistical methods, and mathematical modeling to integrate large-scale experimental biological and clinical data across temporal and spatial scales to better understand infectious diseases. Brown has considerable experience in the omics of infectious diseases and computational biology through her academic career at Trinity Washington University and research at the J. Craig Venter Institute. Prior to joining NIAID in 2016, she was associate director of Scientific Affairs at the Society for Women’s Health Research.

Brown received a bachelor’s degree in biochemistry from the University of Illinois, Urbana and a doctoral degree in cellular and molecular biology from the University of Maryland, College Park.

Mariana Byndloss is an assistant professor of pathology, microbiology, and immunology at Vanderbilt University Medical Center. Her current work proposes to establish novel molecular mechanisms responsible for the imbalance in the intestinal microbial community (dysbiosis), which connects major players in the pathogenesis of non-communicable diseases and salmonellosis. She is particularly interested in how inflammation-mediated changes in gut epithelial metabolism lead to gut dysbiosis and increased risk of non-communicable diseases, namely inflammatory bowel disease, obesity, cardiovascular disease, and colon cancer.

A native of Brazil, Byndloss earned her doctorate of veterinary medicine and master’s degree in veterinary pathology from Universidade Federal de Minas Gerais (UFMG). Her doctoral work, performed at UFMG and the University of California, Davis (UCD), was awarded the Brazilian National Prize for best PhD thesis in veterinary medicine. She performed her postdoctoral training in Andreas Bäumler’s laboratory at UCD studying the link between endoplasmic reticulum stress and innate immunity as well as the interactions between the host and intestinal microbiota during dysbiosis.

Melissa Cregger, PhD Phillip J. Daschner, MS

Melissa Cregger is a staff scientist in the Biosciences Division at Oak Ridge National Laboratory (ORNL). She is an ecologist broadly interested in understanding microbial community dynamics across ecosystems, and how changes in microbial community structure may influence microbial function. Specifically, she is interested in understanding the potential for changes in microbial diversity and composition to influence large-scale nutrient fluxes and the health of associated host organisms, both plant and mammalian. Her research spans scales from the molecule to the ecosystem level, taking advantage of modern techniques to fully understand microbial interactions.

Cregger received her PhD in ecology and evolutionary biology in 2012 from the University of Tennessee under the guidance of Aimee Classen. After her PhD, she was a post-doctoral fellow in biocomplexity at the Carl Woese Institute for Genomic Biology at the University of Illinois, Urbana, where she expanded the focus of her work to examine host-microbe interactions in mammalian hosts. In 2014, she began a post-doctoral appointment with Chris Schadt, ORNL senior staff scientist in the Biosciences Division, and received a staff appointment there in 2015.

Phil Daschner is a program director in the Division of Cancer Biology at the National Cancer Institute (NCI) in the National Institutes of Health (NIH). He manages a portfolio of basic research grants on mechanisms of biologic carcinogens for the Cancer Immunology, Hematology, and Etiology Branch at NCI. He also holds leadership roles on both the trans-NIH Microbiome Working Group and the trans-NCI Microbiome Working Group, which coordinate ongoing microbiome-related initiatives and activities at the NIH and institute levels. He has organized NIH-sponsored international meetings and workshops on microbiome-related topics, co-authored several meeting reports, and authored a textbook chapter on the microbiome’s effects on cancer therapy.

Daschner received his graduate training in cell and microbiology from Arizona State University and has a background in microbial genetics and drug discovery from natural products. This work includes the initial purification and testing of bryostatin from marine invertebrates, and the identification of dietary components curcumin and resveratrol as natural ligands of the aryl hydrocarbon receptor.

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Tian Hong, PhD Shannon Hughes, PhD

Tian Hong is an assistant professor in the Department of Biochemistry and Cellular and Molecular Biology (BCMB) at the University of Tennessee, and a core faculty member in the National Institute for Mathematical and Biological Synthesis (NIMBioS). Hong is a computational biologist interested in using mathematical and computational approaches to understand complex biological systems. His current research focuses on mathematical modeling for multistep cell fate transitions, including the epithelial-mesenchymal transition (EMT), a reversible process that is critical for development and cancer progression.

Using information about gene regulatory networks, he has built mathematical models that predict the stable intermediate states between epithelial and mesenchymal states. He is currently developing a multiscale framework to model the plasticity of epithelial cells in terms of transcriptional control, cellular state transitions, and cell motility, modeling approaches that will be useful for understanding the complex roles of transcriptional regulations in dynamics of epithelial cells and in metastasis.

Before joining UT, Hong obtained his doctoral degree in genetics, bioinformatics, and computational biology from Virginia Tech, and completed his postdoctoral training in the Department of Mathematics at the University of California, Irvine.

Shannon Hughes joined the National Cancer Institute (NCI) Division of Cancer Biology in 2015 as a program director for the Cancer Systems Biology Consortium (CSBC) and the Physical Sciences in Oncology Network. Her interest in cancer systems biology and physical oncology stems from her background in applying chemical and biomedical engineering principles to investigate cell signaling pathways involved in cell migration, invasion, and cancer metastasis. She is co-lead of the Human Tumor Atlas Network and manages CSBC, NCI’s main effort to tackle complex questions in cancer through the explicit integration of mathematical and computational approaches with experimental biology.

Following completion of her bachelor’s degree in chemical engineering from Iowa State University, Hughes spent three years as a process engineer working in the field of drug delivery at 3M in St. Paul, Minnesota. Industrial research motivated her doctoral degree in biomedical engineering at Washington University, St. Louis, where she studied the molecular mechanisms underlying bioactive sphingolipid-mediated endothelial cell migration. After moving to the Massachusetts Institute of Technology (MIT), she obtained a Department of Defense post-doctoral fellowship in breast cancer research to systematically investigate the role of the cytoskeleton in receptor tyrosine kinase-mediated breast cancer metastasis. Before coming to NCI, Hughes co-authored many research publications in both experimental and quantitative biology, mentored undergraduate and graduate level students, and served as a lead technical research instructor in the Biological Engineering Department at MIT.

Rachel Patton McCord, PhD

Rachel Patton McCord is an assistant professor in the Department of Biochemistry and Cellular and Molecular Biology (BCMB) at the University of Tennessee. Tying together the physical and genetic roles of 3D genome structure, her work combines genomic, microscopy, and computational approaches to characterize the interplay between chromosome structure and nucleus shape changes during cancer cell metastasis or in the premature aging disease progeria.

McCord received a bachelor’s degree in biophysics from Davidson College and a doctoral degree in biophysics from Harvard University. She began working with large-scale genomic data under the mentorship of Martha Bulyk at Harvard, analyzing transcription factor sequence preferences from protein binding microarray data. After encountering the complexity of human gene regulation and the incomplete predictive value of linear DNA sequence, she pursued post-doctoral work with Job Dekker in systems biology at the University of Massachusetts Medical School to explore the additional layers of regulation encoded in the 3D folding and looping of the human genome. Her discoveries about the role of 3D genome structure in cancer, DNA damage response, and premature aging continue to motivate her research at UT.T

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Grace C.Y. Peng, PhD

Grace C.Y. Peng is the director of Mathematical Modeling, Simulation, and Analysis at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) within the National Institutes of Health (NIH). Since 2002, she has been a program director in the NIBIB, overseeing various programs promoting the development of mathematical and statistical modeling and analysis methods, medical simulation tools, and next generation engineering systems for rehabilitation, robotics, neuroengineering, and surgical systems.

In 2003, Peng led the creation of the Interagency Modeling and Analysis Group (IMAG), which now consists of program officers from multiple federal agencies of the US government. Since 2004, IMAG has supported funding initiatives targeted to multiscale modeling of biomedical, biological, and behavioral systems. Since 2006, IMAG has facilitated the activities of the Multiscale Modeling Consortium of investigators. She is committed to promoting the development and use of intelligent tools and reusable models to accelerate biomedical research and translate scientific knowledge to the clinic and community.

Peng received a bachelor’s degree in electrical engineering from the University of Illinois at Urbana, and master’s and doctoral degrees in biomedical engineering from Northwestern University. She performed postdoctoral and faculty research in the Department of Neurology at the Johns Hopkins University. Before joining the NIH, her research focused on developing computational models of the vestibular system in control of the head and neck, and analytical tools for studying the oculomotor system in patients with vestibular dysfunction.

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Joseph F. Pierre, PhD

Joseph Pierre is an assistant professor in the Department of Pediatrics at the University of Tennessee Health Science Center. An experimental biologist and gastrointestinal physiologist interested in how gut microbial communities (bacteria, yeast, and fungi) and their metabolites influence host homeostasis, he runs a translational science research laboratory focused on how microbes influence outcomes in bariatric surgery and how early life microbial colonization influences adolescent obesity risk. He also directs the only germ-free/gnotobiotic mouse facility in Tennessee. Using germ-free mice, his lab explores the causal role that microbes play in orchestrating host metabolism by colonizing animals with defined microbial communities. He holds a joint appointment as an assistant professor of microbiology, immunology, and biochemistry and is a faculty member of the Biomedical Science Program in the Graduate Health College.

Pierre received his bachelor’s and doctoral degrees from the University of Wisconsin at Madison, where he studied parenteral nutrition and gut immunity. He completed a postdoctoral fellowship in gastroenterology, hepatology, and nutrition at the University of Chicago under the mentorship of Eugene B. Chang, where he explored the gut microbiome and mycobiome interactions with host metabolism and immune function.

Veerasamy (Ravi)

Ravichandran, PhD

Eric A. Stahlberg, PhD

Ravi Ravichandran is a program director in the Division of Biophysics, Biomedical Technology, and Computational Biosciences in the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health (NIH). He manages research and training grants in bioinformatics and computational biology and oversees the Initiative for Maximizing Student Development program. He is also involved in facilitating and coordinating trans-NIH activities related to big data.

Ravichandran earned a bachelor’s degree in chemistry, master’s degrees in biochemistry and philosophy/clinical biochemistry, and a doctoral degree in biochemistry from the University of Madras in India. He also has a master’s degree in computer science and bioinformatics from John Hopkins University and a certificate degree in database development from George Washington University. Earlier in his career, Ravichandran was a staff scientist at NIH’s National Institute of Neurological Disorders and Stroke, a research scientist at the National Institute of Standards and Technology, and an associate research scientist at Yale University School of Medicine and the University of Pennsylvania.

Eric Stahlberg is the director of Biomedical Informatics and Data Science (BIDS) at Frederick National Laboratory for Cancer Research (FNLCR), where he has been instrumental in establishing the Frederick National Laboratory (FNL) high performance computing initiative and in assembling scientific teams across multiple, complex organizations to advance predictive oncology.

Stahlberg first joined the FNL in 2011 to form and direct the National Cancer Institute (NCI) Center for Cancer Research Bioinformatics Core, which helped build intramural research collaborations between the FNL and NCI. Since then, he has held leadership positions in several major partnerships, including the Joint Design of Advanced Computing Systems for Cancer (JDACS4C), a major collaboration between the NCI and the Department of Energy (DOE) to accelerate progress in precision oncology and computing. The collaboration is rooted in three major national initiatives: The Precision Medicine Initiative, the National Strategic Computing Initiative, and the Cancer Moonshot. Stahlberg has spearheaded FNL contributions to a number of JDACS4C projects, including Accelerating Therapeutics for Opportunities in Medicine (ATOM) and the Cancer Distributed Learning Environment (CANDLE). He helped launch and support the annual meeting series, “Frontiers in Predictive Oncology and Computing.” In 2017, he was recognized as one of Federal Computer Week’s (FCW) Federal 100 for his leadership in advancing government agency missions through information technology. Stahlberg holds a PhD in computational chemistry from the Ohio State University.

Mircea Podar, PhD

Mircea Podar is a distinguished staff scientist and leader of the Systems Genetics Group in the Biosciences Division at Oak Ridge National Laboratory (ORNL). He uses a wide range of experimental and computational approaches that combine single cell genomics and metagenomics with cultivation and characterization of novel microorganisms from various environments, including the human body. Podar was involved in the original National Institutes of Health (NIH) Human Microbiome Project and contributed to several of the seminal studies published under that initiative. His current research on the human microbiome focuses on understanding interspecies interaction in health and disease (including cancer), primarily in the oral microbiome, and cultivation of novel organisms using genomic information. As most microbial lineages from many environments are still uncultured, the overarching theme of his research is the development of novel approaches that use genomic data from genomes and metagenomes to isolate and study microbial “dark matter.”

Podar received his doctoral degree from the University of Texas Southwestern Medical Center, where he studied the biochemistry and molecular genetics of mitochondrial catalytic RNAs. Following post-doctoral studies at Woods Hole Oceanographic Institution focused on molecular evolution, and at the Salk Institute in La Jolla on molecular virology, he was a bioinformatics scientist at Diversa Corporation in San Diego. At Diversa, Podar focused on microbial evolutionary genomics and enzyme evolution and pioneered work in the emerging fields of metagenomics and single cell genomics. He joined ORNL in 2007.

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S Cemal Erdem | Clemson UniversityBig Modeling of Big Data to Understand Cells’ Signal Integration

and Decision-Making

Ryan Beni | Tennessee State UniversityAminoglycoside Antibiotic-Peptide Conjugates to Overcome Drug

Resistance: An In Silico Study

Anfal Haris | Tennessee Technological University Role of Pre-Electrophoresis in Tailoring Hydrogel Structure for

Health Care Applications

A. Nastasia Allred | Tennessee Technological UniversityMathematics-Assisted Medicine (MAM): The Use of Integral-

Spectral Methods in Predicting Hyperthermia Treatment Behaviors

of Cancerous Tumors

Samantha Blanton | Tennessee Technological University Assessing the Effectiveness of Drug Delivery to Stage III

Pancreatic Cancer Domain

Karl Leitner | University of Tennessee Using Microbes to Break Down Carcinogenic Chemicals

Rosela Golloshi | University of Tennessee 3D Genome Organization Changes Associated with Melanoma

Confined Migration

Gabriel Fuente | University of Tennessee Ligand Binding Studies of a Trimethoprim-Resistant Dihydrofolate

Reductase by Fluorine NMR

Veronica Brown | University of Tennessee The University of Tennessee Genomics Core and Bioinformatics

Resource Center

Yang Xu | University of Tennessee Examining Cell Variation at Multiple Levels by Hi-C, DNase-seq,

RNA-seq, and ChIP-seq

Michael Duff | University of Tennessee Biguanide Inhibition of Dihydrofolate Reductases

Deepika Nambiar | University of Tennessee The Effect of Excipients on Medically Important Folate Enzymes

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Tingting Xu | University of TennesseeReal-Time Tracking of Bacteria-Human Cells Interaction Using

Autobioluminescence

Steven Ripp | University of TennesseeLive Animal and Biomedical Imaging Resources at the University of

Tennessee

Sean Callahan | University of TennesseeLipocalin-2 Upregulation in Response to Campylobacter Jejuni Infection

Jacob Sanders | University of TennesseeRadiation-Induced DNA Damage Effects on Chromatin Organization

Amber Smith | University of Tennessee Health Science CenterThe Nonlinear Relations that Predict Influenza Viral Dynamics, CD8+ T

Cell-Mediated Clearance, Lung Pathology, and Disease Severity

David Levine | University of Tennessee, ChattanoogaEnvironmental Bacterial Contamination in Children’s Hospitals and

Recommendations for Remediation

Mehran Ghafari | University of Tennessee, ChattanoogaDeveloping an Automated Method to Estimate Yeast Cells’ Replicative

Lifespan from Time-Lapsed Microfluidic Images Using Machine Learning

Henry Spratt | University of Tennessee, ChattanoogaEnvironmental Bacterial Contamination in a Children’s Hospital: The

Importance of Culturable vs Non-Culturable Bacteria to Healthcare-

Associated Infection

Stephen Grady | University of TennesseeAn Integrated Metagenomics/Metaproteomics Approach to Gut

Microbiome Metabolic Networks for Preterm Infants with and without

Necrotizing Enterocolitis

Carissa Bleker | University of TennesseeMetabolic Models for Escherichia Coli Phylotypes

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Gladys AlexandreUniversity of Tennessee

Heidi Goodrich-BlairUniversity of Tennessee

Martha S. HeadOak Ridge National Laboratory

David G. WhiteUniversity of Tennessee Institute of Agriculture

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