We are an interdisciplinary research group at the interface of carbohydrate research and immunology. Our objective is to explore treatment of and protection from infectious diseases and cancer by understanding key molecular and cellular interactions between the components of the immune system and carbohydrate antigens associated with microbes or cancers.
Our research program is directed at: delineating immune mechanisms involved in carbohydrate-mediated adaptive immune response, and designing, synthesizing and testing vaccine targets against model pathogens and cancers. Our research approach involves: (1) identification of the molecular interactions involved in uptake, processing and presentation of carbohydrate antigens by the antigen presenting cells (APCs), (2) isolation and characterization of T cells and their epitopes generated from model carbohydrate antigens, (3) understanding the basis for cellular and humoral immune responses induced by carbohydrate presentation and recognition that enable eradication of disease causing agents, (4) design and synthesis of new-generation therapeutic and/ or prophylactic agents based on the knowledge gained from mechanisms discovered.
Heme is a key and essential compound for the vast majority of living organisms. Heme, as a cofactor in a variety of proteins, is widely acknowledged to be essential for gas transport, respiration, xenobiotic detoxification, peroxide production and destruction, fatty acid desaturation, and a variety of one electron transfer reactions. Over the past decade the number of roles identified for heme has grown substantially. It has become clear that heme is also an important intracellular regulatory ligand. Among the list of biological processes for which higher eucaryotic heme-binding proteins have now been implicated is regulation of circadian rhythm, adipogenesis, glucose homeostasis, microRNA processing, gas sensing, control of ion channels, and intra- and intercellular signal transduction. The list of bacterial heme-binding sensors seems to grow with each new journal publication, and the role of the heme-containing DevS-DevR proteins of Mycobacterium tuberculosis as regulators of passage into the dormant stage has attracted considerable attention for obvious biomedical reasons. Dietary heme also serves as a significant source of iron for many organisms including pathogenic bacteria. A search of PubMed for “heme” yields over 2500 listed publications in the past year. The Dailey lab’s research focuses on the enzymes responsible for heme biosynthesis. Current studies involve structure/function investigations of the terminal enzymes of heme biosynthesis and their relationship to the human genetic diseases known as porphyrias, biochemical characterization of the enzymes from both eukaryotic and prokaryotic organisms, identification and characterization of novel and previously unidentified genes involved in heme synthesis and transport, protein-protein interactions among heme synthesis enzymes, and regulation of expression and translocation of heme synthetic enzymes.
Our work focuses on the generation of therapeutically useful cell types that can be used to treat cardiovascular disease, diabetes, stroke, autoimmune disease, spinal cord injury and neurological diseases. We are also interested in early development and how pluripotent cells contribute to the developing embryo. For further information, visit our lab website: www.daltonlab.uga.edu
The Edison lab develops new approaches in metabolomics and natural products research. Our primary research tool is NMR spectroscopy, but we regularly collaborate with experts in mass spectrometry. A major focus is on data integration between NMR, MS, and other quantitative measurements. We have numerous applications, primarily through collaborations.
Exploring molecular mechanisms underlying cell-cell communication between African trypanosomes and host cells. Evaluation of the mechanism of human innate immunity to African trypanosomes. Analysis of the function of RNA editing in the mitochondrion of African trypanosomes.
We study how protein glycosylation affects cellular communication as well as protein folding using biochemical, cell biological and animal studies. The forms of glycosylation we study affect development, birth defects, and cancer.
Research in my lab is at the intersection of genome biology, evolutionary biology and computational structural biology. We combine techniques and approaches from these diverse disciplines to understand the underlying mechanisms of signaling proteins in atomic detail.
Research in the Moremen lab focuses on the structure, enzymology, regulation, and localization of enzymes involved in the biosynthesis, recognition, and catabolism of mammalian glycoproteins. Carbohydrate structures on glycoproteins contribute to many biological recognition events between molecules and between cells in an organism. Alterations in the synthesis and degradation of these structures can also occur in human genetic disease. Work in the Moremen lab is focused on (1) the characterization of enzymes involved in mammalian glycoprotein biosynthesis and catabolism and the functionally defective forms of these enzymes involved in human genetic disease and (2) the identification and characterization of carbohydrate-binding proteins and their roles in vertebrate development and physiology.
Our laboratory employs recombinant technology to investigate the role of beta amyloid peptide fibrilization in the onset of Alzheimer
X-ray structural biology, protein structure determination by Native-SAD, structural investigation of components the mitochondrial inner membrane space transport system, structure based vaccine and therapeutic design.
We are trying understand how the protozoan parasite, Trypanosoma brucei, regulates telomeric gene expression and evades the host immune response. Our current focus is on the role of the novel DNA base, base J, and in regulating telomeric homologous recombination events.
Research in our lab is mainly focused on proteases:
- The CaaX proteases: Rce1 and Ste24 mediate a proteolytic cleavage event associated with the maturation of proteins that contain a covalently attached isoprenyl lipid at their C-terminus (e.g. Ras, nuclear lamins, fungal pheromones). We are investigating the mechanism and specificity of these proteases in an effort to better understand their role in human disease (e.g. Ras and cancer; lamins and progeria).
- The M16A proteases: This evolutionarily conserved metalloprotease family includes the human insulin-degrading enzyme, which mediates degradation of amyloidogenic peptides such as the Abeta peptide associated with Alzheimer’s disease. We are investigating the mechanism and specificity of these enzymes to better understand their physiological role in the cell.
Our research program is multi-disciplinary, allowing for exposure to the disciplines of biochemistry, cell biology, chemistry, genetics, and microbiology.
Our laboratory utilizes multiple model systems including zebrafish to study the developmental consequences of impaired lysosomal catabolism of glycoproteins. We are focused on understanding how the mislocalization and inappropriate activity of specific enzymes impacts the normal development and function of several tissues including cartilage.
RNA-guided invader defense in prokaryotes: Archaea and bacteria (both pathogenic and beneficial) are constantly attacked and destroyed by viruses and other genome invaders. We are working to delineate a series of newly-identified RNA-mediated immune systems that protect prokaryotes from viruses and other invaders - the CRISPR-Cas systems. This exciting research is leading to new ways to strengthen beneficial microorganisms that produce food, pharmaceuticals and biofuels, to combat disease-causing bacteria, and to prevent the spread of antibiotic resistance.
Our research focuses on protein structure and function and protein-protein interactions. We employ an approach combining modern analytical, biophysical and molecular biology techniques, with an emphasis on biomolecular NMR spectroscopy. Our core projects include the study of gene regulation and novel regulators of transcription initiation in bacteria, oxidative stress and calcium signaling, steroid hormone (estrogen) receptor activation, and regulation of biofilm formation and pathogenesis in Pseudomonas aeruginosa. These projects are important fundamentally, and they important biomedically with respect to antibiotic target development, oxidative stress and biological aging, and diseases such as breast cancer and cystic fibrosis.
Research in the Wang laboratory focuses on the structure and function of heparan sulfate proteoglycans in vasculature and cancer biology. Heparan sulfate proteoglycans are glycoconjugates which are abundant on the cell surface and in the extracellular matrix. In vitro studies have suggested that heparan sulfate proteoglycans interact with growth factors, growth factor binding proteins, extracellular proteases, protease inhibitors, chemokines, morphogens, and cell adhesive proteins to modulate cell differentiation, proliferation, migration, blood coagulation, lipid metabolism, and leukocyte trafficking. However, the biological and pathological functions of heparan sulfate proteoglycans in vivo are still largely unknown. Using techniques, including conditional mouse gene targeting, embryonic stem (ES) cell differentiation, primary cell culture, and mouse models, the Wang lab is aiming to understand the roles and the underlying mechanisms of heparan sulfate proteoglycan in vascular development, cancer biology and blood coagulation in vivo, and to develop novel approaches to cure the related pathological conditions.
Our laboratory is interested in how post-translational modifications of proteins increase functional diversity. Primarily, we are interested in glycosylation, with a focus regarding: 1. O-GlcNAc in Type II diabetes and stem cell biology 2. O-Mannosylation in Congenital Muscular Dystrophy and viral entry into host cells 3. Glycoproteins as biomarkers in human disease, specifically pancreatic cancer and metabolic syndrome 4. Development of technology-based approaches, primarily mass-spectrometry, for quantitive proteomics/ glycomics/ glycoproteomics.
The focus of my group's research is to examine the relationships between carbohydrate conformation and biological recognition and activity. We are particularly interested in the mechanisms of carbohydrate recognition in the immune system. Current research projects include examinations of bacterial antigen-antibody interactions, as well as other carbohydrate-protein interactions. The carbohydrate antigens associated with bacteria, such as Salmonella paratyphi B and group B Streptococcus are being studied in order to quantify the contributions made by hydrophobic and hydrophilic interactions. In conjunction with experimental methods (NMR and X-ray), we apply molecular dynamics simulations with the GLYCAM parameters and the AMBER force field.