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Petit Institute Breakfast Club Seminar Series

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Now showing 1 - 8 of 8
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    The Center for Integrative Genomics and Predictive Health in Atlanta
    (Georgia Institute of Technology, 2010-11-09) Gibson, Greg
    I will give a two-part talk that starts with a discussion of my groups research on genomic profiling in human populations, and leads to a presentation of my vision of the relationship of the Center for Integrative Genomics to the IBB and Systems Biology programs at Georgia Tech. We are broadly interested in the question of how environmental and cultural factors interact with genetic predisposition to shape human phenotypic variation, from gene expression in peripheral blood to facial expression in growing infants. Genomic profiling is built around genome-wide association studies (GWAS) of gene expression, metabolomics, and epigenetic marks in a variety of cohorts available through collaborators at Emory and our own contacts in places like Fiji and Morocco. I'll discuss the Center for Health Discovery and Wellbeing cohort at Emory midtown, as well as initiatives in cystic fibrosis, cardiology, cancer survivorship, and newborn children.
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    Novel Strategies for Treating Cardiac Dysfunction
    (Georgia Institute of Technology, 2010-10-12) Davis, Michael E.
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    Designing Cell Instructive Extracellular Matrices
    (Georgia Institute of Technology, 2010-09-14) Barker, Thomas H.
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    Biomechanics and Remodeling in Native and Engineered Arteries
    (Georgia Institute of Technology, 2010-04-20) Gleason, Rudolph L.
    Despite advances over the past 25 years, a pressing clinical need remains to develop small diameter tissue engineered blood vessels (TEBV) with low thrombogenicity and immune responses, suitable mechanical properties, and a capacity to remodel to their environment. One promising technology for developing a TEBV is the self-assembly approach. This approach consists of culturing vascular cells to form sheets of cells and extracellular matrix, then rolling these sheets around a mandrel and culturing them to form a tubular structure. Sheets made from different cell types (e.g. SMCs versus fibroblasts) can be combined to produce heterogeneous vessels containing media-like and adventitia-like layers; vessels may also be seeded with endothelial cells to form a functional endothelium. This presentation reviews recent studies conducted in our lab that characterize the biomechanical properties of both native arteries and engineered tissues and the implications of these findings on defining appropriate design criteria for a coronary by-pass graft. Biomechanical testing and parameter estimation to characterize the mechanical behavior of the media-like and adventitia-like self assembly-derived TEBV are be presented and compared to TEBV constructed from competing tissue engineering strategies (e.g., collagen gels), as well as representative data from human coronary arteries taken from the literature. The predictive capability of the constitutive model is be demonstrated by comparing modeling predictions to experimental data from two-layer self assembly-derived TEBV. Finally, modeling results are presented to test novel fabrication strategies to control the mechanical behavior of self assembly-derived TEBV.
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    Human Repetitive DNA Sequences as a Source of Chromosomal Fragility and Genome Rearrangements in Yeast: Implications for Human Polymorphisms and Diseases
    (Georgia Institute of Technology, 2010-02-16) Lobachev, Kirill
    Eukaryotic chromosomes must be accurately maintained, duplicated and segregated during mitotic and meiotic divisions to guarantee inheritance of the correct genetic information by the daughter cells. However, occasionally genome integrity can be compromised: chromosomes break and rearrange which can cause drastic changes in the way how genes are expressed. This type of genetic instability is a causative factor in the development of many hereditary diseases and cancers in humans. On the other hand, the ability of chromosomes to undergo breakage and rearrangements promotes genetic variations that contribute to species polymorphisms and evolution. Multiple environmental and intracellular factors such as ionizing radiation, UV light or reactive oxygen species are well-established damaging agents that can fracture chromosomes at any position and trigger chromosomal abnormalities. Nevertheless, work over recent years has established that breaks along the chromosomes do not occur randomly but rather often coincide with the regions containing repetitive elements capable of adopting non-canonical DNA secondary structures. The enigmatic discovery that DNA repeats which can be inherited or occur de novo are a very powerful source of the breakage and rearrangements adds new perspective to our understanding of the origin of human pathology, polymorphism and evolution. Why breaks happen, what genetic and environmental factors contribute to fragility, what are the consequences of these types of breaks for the integrity of the eukaryotic genome? Those are the questions that we are trying to address using yeast as a model eukaryotic organism in my laboratory. I will present our new findings related to three sequence motifs that can adopt different secondary structures. The underlying mechanisms of repeat-mediated breakage uncovered in yeast can be extrapolated to the studies of chromosomal dynamics of higher eukaryotes including humans.
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    Towards an Evolutionary Synthetic Biology
    (Georgia Institute of Technology, 2009-11-10) Gaucher, Eric A.
    Evolution is the unifying theory behind biology, and has entered the mainstream of computational and molecular biology as a result of genomics. Nevertheless, evolutionary ideas today only barely influence the practice of molecular sciences. Innovation in many areas will be required before evolutionary analyses provide utility to biomedicine and biotechnology. Research in our laboratory attempts to enhance our understanding of evolutionary processes and structure-function relationships in the long-term, while also generating novel biomolecules having technological and therapeutic value in the short-term. If successful, these innovations will add utility to genome sequence data far beyond that found in comparative genomics. Using information extracted from molecular evolutionary analyses to guide the engineering of proteins is an innovative addition to existing methods. If evolution-guided engineering can deliver biomolecular properties not otherwise attainable with traditional engineering/directed evolution techniques, then this approach will have wide utility. The above activities form the foundation of our attempt to develop an evolutionary synthetic biology. We are energized by the prospect of joining evolutionary biology and synthetic biology. Synthetic biology appears to mean different things to different scientific disciplines. Surprisingly, however, biologists seem to have taken a backseat to chemists and engineers in the development of this field. It seems apparent that synthetic biology would stand to benefit if molecular evolution contributed to its progress.
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    Engineering Stem Cell Technologies
    (Georgia Institute of Technology, 2009-04-21) McDevitt, Todd C.
    The McDevitt laboratory is focused on the engineering of innovative technologies to translate the regenerative potential of stem cells into effective cellular and molecular therapies for the treatment of degenerative diseases and traumatic injuries. By developing controlled systems approaches to engineer the microenvironment of stem cells, we aspire to improve the efficiency and yield of directed stem cell differentiation strategies. We also seek to develop novel regenerative molecular therapies based on the morphogens produced by stem cells. Efficient scalable bioprocesses will require the development of enabling tools and technologies to facilitate the production of stem cell technologies. The combination of directed stem cell differentiation and derivation of stem cell biotherapeutics will yield fresh insights into stem cell biology and facilitate new regenerative therapies.
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    Evolutionary Role of DNA Methylation in Animal Genomes
    (Georgia Institute of Technology, 2008-10-21) Yi, Soojin V.
    DNA methylation is a primary epigenetic mechanism involved in several regulatory and developmental processes. In this talk, I will focus on the molecular evolutionary role of DNA methylation. An important property of DNA methylation is its propensity to increase specific types of point mutations. Using this property, we have developed analytical tools to investigate influence of DNA methylation on genome evolution. We show that (i) DNA methylation causes different genomic regions to follow qualitatively different molecular clocks, (ii) influence regional variability of nucleotide composition, (iii) affected evolution of vertebrate promoters. Finally, (iv) our survey shows that the influence of DNA methylation on genome evolution is widespread in animal taxa. While the model invertebrate species Drosophila melanogaster and Caenorhabditis elegans lack DNA methylation, the genome of a social bee Apis mellifera exhibits an unmistakable signature of DNA methylation at sequence and functional level.