Georgia Tech News, Seminars, Events

Cancer Research at Georgia Tech:

Georgia Tech Research Horizon Feature Articles on:

John McDonald joined us in July 2004 as our new Chairman! Dr. McDonald is formerly Head of the Genetics Department at the University of Georgia and former acting Director of the Institute of Bioinformatics at UGA. He is also Chief Scientific Officer of the Ovarian Cancer Institute (OCI) based in Atlanta. He had been Professor of Genetics at UGA since 1990 and Associate Professor from 1982-90. He received his PhD in Genetics in 1977 from the University of California Davis.

The McDonald laboratory is interested in understanding the mechanisms underlying retroelement evolution and the impact these elements have had on the evolution of the host genomes in which they reside. They combine molecular biology and computational genomics to address these questions in a variety of organisms ranging from yeast to humans.Retrotransposons are the most abundant and wide spread class of eukaryotic transposable elements. For example, retrotransposons constitute ~10% of the Drosophila genome, ~20% of the rice genome, ~40% of the human genome, ~50% of the maize genome and >90% of the genome of some lilies.

His laboratory's interests in retrotransposons extends to the role these elements may play in the alteration of chromatin structure and other epigenetic changes associated with tumorgenesis. In collaboration with the Ovarian Cancer Institute (Atlanta), they are engaged in efforts to identify molecular markers of early staged ovarian cancers using microarray (Affymetrix), 2-D gel and mass spectrometry (MALDI-TOF) technologies. They are also nterested in analyzing the molecular responses of different stages and classes of tumors to chemotherapy and in understanding the molecular basis of chemotherapy resistance.

Dr. Streelman received his Ph.D. in Biology from the University of South Florida in 1988. Since 2001 he has been a postdoctoral fellow at the University of New Hampshire's Hubbard Center for Genome Studies.

Research in the Streelman lab seeks creative solutions to general problems in evolutionary biology. They want to know how evolution works at multiple levels of biological organization. The main study system is the cichlid fish assemblage of Lake Malawi, East Africa, where as many as 1,000 species have evolved in the last 500,000 years. They study cichlids in the field, in the laboratory, and in our tropical aquarium facilities. Their major research goals are to apply novel approaches to understand the genetic and developmental basis of cichlid phenotypes, and to use the cichlid model to learn new things about basic biological processes. Research is presently focused on the evolution of jaws, teeth and color pattern because these traits have been important to cichlid diversification.

In the past few years, theyhave built an array of genomic resources to complement decades of natural history information. Using these tools in the context of wild cichlid populations, they aim to bridge the gap between ecology, genetics and development; and to create unique opportunities for cross-disciplinary teaching and collaboration. For example, theyendeavor to work with GIT engineers, combining evolutionary genetics and biomechanics to understand cichlid jaws and teeth as dynamic, integrated and evolving functional systems.

Dr. Yi received her Ph.D. in Ecology and Evolution from the University of Chicago in 2000 and was a Research Associate there since that time. Dr. Yi's research interests center on evolutionary genomics and molecular evolution.

Her work focuses on understanding the genetic basis of naturally occurring variation within and between species. What causes differences between individuals in phenotypic traits (such as hair color, smell, disease susceptibility and so on), and how do these variations within a species relate to the evolution of different species? The evolution of human specific traits is an especially exciting example of such topics. Her lab uses multidisciplinary approaches, ranging from computational methods to advanced biochemical analyses.

Some current computational projects in herlaboratory are to understand rates and patterns of molecular evolution in the whole genome level and to understand the determinants of spatial distributions of genes and other elements in the mammalian genomes. Another topic in her laboratory is to understand evolution of non-coding regions of primate genomes. Non-coding (not encoding amino acid sequences) parts of genome have been regarded as largely non-functional, until recently. This is true for most of the non-coding genomic regions, in which mutations do not have any effect on its holders’ fitness, in other words, ‘neutral’. However, comparative analyses of complete genomes suggest otherwise. For example, protein sequences between relatively distant mammalian species, such as human and mouse, are very similar, in fact too similar, leading to the inference that the protein sequence differences are insufficient to explain differences between species. Also, some non-coding regions have avoided accumulating mutations and stay conserved in various mammalian species. This can only be explained by the presence of natural selection, to keep these nucleotides intact. We are interested in contrasting different evolutionary rates and patterns between ‘neutral’ and ‘functional’ non-coding regions of primate genomes. This project involves both experimental and computational work.

Dr. Frank Loeffler from the Georgia Institute of Technology won the Strategic Environmental Research and Development Program (SERDP) Project of the Year 2004 award.

The Department of Defense (DoD) recognized Dr. Loeffler's contributions to innovative cleanup strategies for chlorinated solvents, which have become the single largest cost driver in the DoD groundwater cleanup program. The research team led by Dr. Loeffler discovered new microbes and applied bioremediation processes that will generate significant cost savings at DoD sites across the country. The award was presented by Mr. Alex Beehler, Assistant Deputy Under Secretary of Defense, Environment, Safety and Occupational Health in Washington D.C. on November 30th. 2004.

Dr. Mark Hay, Teasley Chair in Environmental Biology, was recently awarded a National Undersea Research Center grant entitled, “Herbivore Resistance to Seaweed Defenses and the Effects on Reef Community Structure”. This grant awards not only research funds, but also research boat time and use of the underwater Aquarius lab. Aquarius is an underwater ocean laboratory located in the Florida Keys National Marine Sanctuary. The laboratory is deployed three and half miles offshore, at a depth of 60 feet, next to spectacular coral reefs. Scientists live in Aquarius during ten-day missions using saturation diving to study and explore our coastal ocean. Aquarius is owned by NOAA and is operated by the National Undersea Research Center at the University of North Carolina at Wilmington.

Professor Jeannette Yen and Assistant Professor Marc Weissburg awarded grant from ONR

Dr. Jeannette Yen, Professor, and Dr. Marc Weissburg, Assistant Professor, were just awarded a grant from Office of Naval Research entitled, “Fluid Mechanical and Chemical Cues in Thin Layers: Role in Organizing Zooplankton Aggregations”.

Abstract: We propose to examine the conditions that are conducive to the formation of plankton aggregations to help address the prevalence and importance of thin layers in the world oceans. The goals of the proposed laboratory experiments are to define the mechanisms by which zooplankton may be attracted to thin layers, and to determine which properties of thin layers evoke the orientation response of copepods. The proposed experiments in our newly constructed salt-water flume target naturally-occurring strain rates, velocity differentials, and shear layer thickness (in situ information will be provided via collaboration with Cowles et al.). Target zoo/phyto-plankton species are those observed in thin layers, and chemical cues will match phytoplankton species and concentrations observed in situ.

A series of experimental treatments are planned to isolate the chemical and hydrodynamic signals that induce zooplankton orientation. The anticipated outcomes of the proposed research include: 1) improved understanding of formation and persistence of thin layers and zooplankton aggregations; 2) better appreciation of the balance between physical forcing and biological responses in thin layer formation; 3) data on zooplankton responses that are required for individual-based models of aggregation to thin layer signals; 4) provide information to field studies about the range of physical measurements that must be performed in order to characterize thin layers and to evaluate their spatial and temporal persistence; and 5) help to target field sites having these features by determining thresholds at which relevant signals induce aggregations.

Professor Jeannette Yen and awarded NSF Ocean Technology and Interdisciplinary Coordination grant

Title: A novel apparatus for simulating oceanic turbulence in the laboratory

Jeannette Yen, Professor in Biology, and Donald Webster, Assistant Professor in Civil and Environmental Engineering, have been funded by NSF-OTIC to develop an apparatus to simulate oceanic turbulence in the laboratory. The motivation for the construction of this apparatus is the desire to study the response of plankton to realistic fluid motions. A specific future focus of their research concerns the collapse of the cod fishery on Georges Banks, Gulf of Maine. Successful recruitment into the fishery requires a match between the spatial distribution of larval fish overlapping with their prey both which are members of the plankton. Thus, understanding the consequences of biological and physical interactions in the sea may help predict and better prepare for economic disasters resulting from system perturbations that affect the lower parts of the food chain. As part of their proposed work, the PIs will take advantage of the interdisciplinary nature of this research to design exercises for laboratory experiences in Ecology and Fluid Mechanics that will give students exposure to interdisciplinary work, and hopefully foster an early appreciation for breaking down boundaries between disciplines.

Assistant Professor Igor Zhulin awarded NSF grant to work on function prediction for signal transduction proteins in completely sequenced microbial genomes.

Abstract: High-throughput genome sequencing projects revolutionize our understanding of the biology of organisms and at the same time generate the need for rapid annotation, subsequent biological interpretation of genome sequences and integration of this knowledge into databases of genomic information. Proteins comprising signal transduction networks control many vital functions in any given organism. However, current functional assignments for signal transduction proteins in sequenced genomes fail to provide sufficient information for understanding their biological role. The goal of this research project is to improve prediction of biological functions for signal transduction proteins in prokaryotes and to unravel potentially novel signal transduction mechanisms and pathways. The research objectives are: (1) Identify sensory and regulatory domains of signal transduction proteins in completely sequenced microbial genomes, and (2) Predict and refine biological function for newly and previously identified signal transduction proteins. We proposed to use a systematic computational genomic approach, which incorporates domain architecture analysis, sensitive sequence similarity searches, phylogenetic and genome context considerations, in constructing blueprints of signal transduction systems in completely sequenced microbial genomes. The results obtained will be incorporated into primary databases and will improve significantly annotation of genomic information. Overall, the research proposed in this project will contribute to our understanding of the organization and evolution of biological systems.

Associate Professor Yury Chernoff receives grant from Huntington’s Disease Society of America

Title: Role of protein-protein interactions in cell toxicity of polyQ huntingtin in the yeast model

Abstract: Huntington disease originates from expansion of the polyQ region (encoded by poly-CAG triplets) in the protein called huntingtin. Poly-Q expansion results in huntingtin aggregation into huge insoluble agglomerates, or inclusion bodies, that is accompanies by neuron degeneration. Neither molecular mechanism of expansions nor mechanisms of cell degeneration are known. It has been proposed that cell toxicity could be due to sequestration of important cellular proteins by polyQ-expanded huntingtin.

Overall goal of this proposal is to employ a yeast-based experimental system for studying the role of protein-protein interactions in polyQ toxicity, and identifying the genetic factors that increase the risk of poly-CAG expansions. Our experimental assay is based on two-hybrid interaction between the exon 1 of huntingtin and C-terminal region of the yeast protein Sla1, involved in formation of the cortical actin patches and endocytic vesicles. Sla1 specifically interacts with the polyQ-expanded HD-associated huntingtin derivative but not with wild-type protein containing the normal number of Q residues. Another component of the same endocytosis-associated complex that includes Sla1 is Sla2, a yeast homolog of the mammalian huntingtin-interacting protein (Hip1). This indicates that the interaction between Sla1 and huntingtin may reflect certain biological functions of huntingtin. The specially designed yeast strains provide an easy phenotypic detection assay for the huntingtin-Sla1 interaction. We also possess a plasmid-based system that enables us to assess the aggregation-associated huntintin toxicity in yeast. The specific aims in this proposal are as follows: 1) study the role of ployQ dependent protein-protein interactions in polyQ toxicity; 2) identify human genes whose products counteract polyQ dependent protein interactions and toxicity; 3) identify agents and conditions that promote polyQ expansions in huntingtin.

Associate Professor Yury Chernoff awarded grant from US Civilian Research & Development Foundation (CRDF)

Title: Initiation and transmission of genetically modified prions in yeast

This is an international collaboration with Dr. Inge-Vechtomov's lab at the St. Petersburg University, Russia. The goal of this project is to investigate the mechanism of conversion of the genetically modified derivatives of Sup35 (e. g., prion-forming domain of Sup35 fused to the other proteins) into a prion form.

Dr. Patricia Sobecky is a co-principal investigator on a grant awarded by the Department of Energy’s Natural and Accelerated Bioremediation (NABIR) program. The principal investigator is Dr. Tamar Barkay (Rutgers University). This three-year project aims to investigate the mode(s) of lateral gene transfer (LGT) in the subsurface and the occurrence of metal resistance and LGT among populations of microbes whose metabolic activities result in metal and radionuclide immobilization. Specific questions to be addressed in this DOE project include (1) what are the mechanisms of LGT among subsurface populations? (2) what is the diversity of plasmids and their compatibility determinants in bacteria from subsurface communities? (3) has LGT contributed to metal resistance among strains of iron and sulfate reducing bacteria whose activities immobilize metals and radionuclides? By focusing on LGT and metal resistance (mechanisms) in the subsurface environment, these investigations will expand our body of knowledge on genetic diversity among microorganisms in their natural habitats and on metal homeostasis among anaerobic microbes.

Title: Improving Accuarcy of Gene Prediction Programs of the GeneMark Family with the Bayesian Segmentation Method

Abstract: This research will be done primarily in Russia as an extension of NIH grant #5R01HG00783. The first aim of the project is to use the algorithm that performs sequence segmentation into compositionally homogeneos regions with different length scales as a preprocessor for gene finding program GeneMark. Ideally, it is necessary to derive a number of models and to choose automatically the model relevant for the particular region of the genome during the gene finding in an anonymous sequence. This step alone can immediately increase the efficiency of gene prediction by several percent. Moreover, the compositional segmentation facilitates identification of intergenic regions containing poliadenilation sites and promoters. The second aim of the project is to build a global genomic alignment of two evolutionarily close genome sequences. To this end segmentation should be oerformed on pairs of sequences into segmant pairs with different substitution rates. The third aim of the project is to develop new algorithms of similarity based gene finding. These tools will be used to identify genes in DNA sequences of closely related species and their pairwise alignments. All the software programs will be available for users via the WWW interface.

NSF IGERT award in Chemical Ecology
This is an interdisciplinary graduate fellowship program with studies in Aquatic Chemical Ecology

Dr. DiChristina awarded NSF Biocomplexity grant

Dr. Thomas DiChristina, Associate Professor, was part of a multi-disciplinary project team awarded a grant from the National Science Foundation to develop multifunctional scanning nanoprobes for in situ analysis of biochemical processes at microbe-mineral interfaces.

Abstract: The main objective of the multi-disciplinary project is to develop scanning probe microscopic (SPM) techniques for imaging biochemical processes at microbe-mineral interfaces. Our project fosters interactions between experts in the fields of chemistry, biochemistry, geochemistry, microbiology, fluids and mass transport, microfabrication and spectroscopy. For investigation of complex chemical, biochemical and physical processes at microbe-mineral interfaces, correlation of in situ electrochemical, topographical and optical information is required. Nanoelectrodes will be integrated into atomic force microscopy (AFM) or scanning nearfield optical microscopy (SNOM) tips based on microfabricated cantilevers. Nano-pH-electrodes and mercury/gold amalgam electrodes for Fe2+ detection will be integrated into scanning probe tips to map the microbe-mineral interface. Such multifunctional SPM tips will provide simultaneous topographical, optical and electrochemical information in space and time at the nanometer scale.
Quantitative mathematical modeling and simulation of electrochemical and physical processes occurring during the scanning process is essential for interpreting results. The multifunctional scanning nanoprobes will be used to determine the molecular mechanism of reductive dissolution of Fe(III) minerals by Fe(III)-reducing bacteria or Fe(III) chemical reductants. Bacterial Fe(III) reduction is a relatively recent addition to the suite of anaerobic respiratory processes carried out by microorganisms and is thought to play a significant role in the global biogeochemical cycles of carbon and iron. The molecular mechanism of bacterial Fe(III) reduction, however, is poorly understood. The newly developed analytical techniques may be extended to studies of other environmentally important microbe-mineral interactions, including reductive precipitation of uranium, precipitation of rhodochrosite and siderite and formation of manganese oxides. In addition, multifunctional scanning nanoprobes may be applicable to a wide variety of electrochemically active processes in other disciplines, including biocorrosion, neurophysiology and cell signaling.

Tom DiChristina, DOE Award

Dr. Thomas DiChristina, Associate Professor, was awarded a grant from the Department of Energy to identify the genes required for microbial uranium reduction.

Abstract: Microbial uranium [U(VI)] reduction is an attractive alternative process for bioremediation of uranium-contaminated environments. Traditional uranium remediation processes such as ion exchange, biosorption or biomineralization are often limited by poor extraction efficiency, inhibition by competing ions, production of large volumes of waste or uranium toxicity. Microbial U(VI) reduction, on the other hand, results in precipitation of extracellular UO2, a highly insoluble uranium mineral that remains immobile and non-toxic under anaerobic conditions. Despite its potential for in situ uranium immobilization, the molecular mechanism of microbial U(VI) reduction remains largely unknown. Naturally occurring U(VI)-reducing bacteria include sulfate-reducing, fermentative and metal-reducing bacteria such as Shewanella putrefaciens. We have recently discovered that S. putrefaciens overcomes the physiological problem of respiring on solid terminal electron acceptors such as Fe(III) by targeting Fe(III) terminal reductases to the outside face of the outer membrane where they transfer electrons to solid Fe(III) substrates. A similar physiological strategy may be employed to transfer electrons to soluble terminal electron acceptors such as U(VI), thereby alleviating problems associated with production of insoluble UO2. To address this possibility, we have proposed to use transposon mutagenesis and genetic complementation analyses to identify the genes required for microbial U(VI) reduction. To facilitate these analyses, we have developed a novel screening technique for identification of S. putrefaciens U(VI) reduction-deficient mutants that are unable to grow anaerobically on U(VI) as terminal electron acceptor. The main objective of this DOE grant is to expand the bank of U(VI) reduction-deficient mutants and identify the full set of genes required for microbial U(VI) reduction.

Julia Kubanek, NSF CAREER Award

Julia Kubanek, Assistant Professor was recently awarded a 5-year NSF CAREER Award to train students and postdocs through the study of ecological effects of chemical communication in marine systems.

Title: Chemical communication in marine ecosystems: Interactions involving harmful algae and zooplankton.

Summary: Most organisms use chemical signals to assess their environment and to communicate with other organisms. Chemical cues for the purposes of defense, mate attraction, habitat selection, and food tracking are known to be crucial, widespread, and diverse. As our understanding of receptor-ligand interactions, biosynthetic pathways, sensory biology, hydrodynamics, and ecosystem function has improved dramatically in the last decade, the opportunity to address the chemistry of marine biological processes has become more promising than ever before. This project will focus on the ecological effects of chemical communication in marine systems, demanding significant integration of biology and chemistry, involving active participation of young scientists in hypothesis building and testing, and training students in research methods and communication.
In this study, the Florida red tide dinoflagellate Karenia brevis (= Gymnodinium breve) will be used as a model system for understanding how phytoplankton natural products directly mediate critical interactions such as predation, which affects population and community structure. Phytoplankton chemistry may also induce food-web cascades affecting multiple ecosystems, amplified by the movement of blooms over vast distances. Indirect evidence suggests that some harmful algae use natural toxins to deter grazing by zooplankters, shellfish, and planktivorous fish, or as allelopathic agents against competing microalgae, perhaps contributing to bloom proliferation. This study will test the hypothesis that chemical compounds produced by Karenia brevis defend it against grazing by the co-occurring copepod Acartia tonsa. Chemical fractionation guided by copepod behavioral and physiological feeding assays will be used to isolate antifeedant compounds from K. brevis extracts. Ecologically active compounds will be identified by spectroscopic techniques such NMR spectroscopy and mass spectrometry (including LC-MS). This research will provide adaptable methods for studying food-web and competitive relationships between unicellular organisms and their enemies, effectively decoupling chemical from morphological and nutritional factors.

Students involved in interdisciplinary science need to develop strong communication skills for bridging fields and to acquire a breadth of experience without sacrificing scientific rigor and depth in their specialty. Towards these ends, two new educational opportunities have been designed. First, a new seminar series is planned for graduate and upper-undergraduate students, researchers, and faculty on the intersection of research, policy, and communication with non-scientists, using harmful algal blooms as an example of science that holds public interest. As part of this course, students will engage in a public education exercise to gain skills in communicating science with non-experts, for example by writing an op-ed piece for their hometown newspaper or for internet publication. Second, a new interdisciplinary course will be developed for graduate and upper-undergraduate students on methodologies for the discovery of novel bioactive molecules that function as cues among aquatic organisms. In conjunction with other aquatic signaling courses including a shared laboratory component, this course will lead students to make original research contributions in the field of aquatic chemical ecology.

Center for Bioinformatics and Computational Biology

The Center for Bioinformatics and Computational Biology at Georgia Tech has been recently formed to provide interdisciplinary graduate education and collaborative research in the areas of bioinformatics and computational biology. The Center is comprised of faculty/labs in several departments on the Georgia Tech campus.