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Chemical Biology Specialty Area at U of M Our program emphasizes highly interdisciplinary research and training, aimed at the development and integration of modern chemical methods in order to understand biological problems at the molecular level. Slide 2 Chemical Biology Specialty Area at U of M 19 Faculty Highly Interdisciplinary Research NIH Chemistry and Biology Interface Training Grant (CBITG) Chemical Biology Colloquium Laboratory Rotation Program Slide 3 Engineering Metabolic Pathways Single Cell/ Molecule Studies Biocatalysis & Biomolecular Design Nucleic Acid Chemistry Bioorganic Chemistry Metallobiochemistry Med Chem Chemistry BMBB Microbiology CBITG Areas of Training Slide 4 Chemical Biology Coursework at U of M Flexible program Mechanisms of Chemical Reactions Introduction to Chemical Biology Chemical Biology of Enzymes Nucleic Acids Biochemistry Optional courses (2) Slide 5 Introduction to Graduate Research: Chem 8025 Course Objective Broaden exposure of students to new areas of chemistry by giving them practical hands-on exposure to graduate research in a participating facultys lab Course Description Rotate through two different laboratories. Each rotation lasts approximately seven weeks, with one credit earned for each rotation Slide 6 Research Areas Represented among Chemical Biology Faculty at U of M Bioanalytical & Biomaterials Computational Chemistry Design & Synthesis Enzyme Chemistry Structure & Spectroscopy Nucleic Acids Slide 7 Bioanalytical & Biomaterials Slide 8 Edgar Arriaga Michael Bowser Marian Stankovich Andrew Taton Slide 9 Subcellular distribution 1.2 1.0 0.8 0.6 0.4 0.2 Fluorescence (V) 250200150100 Migration Time (s) Doxorubicin Metabolites Arriaga Group, 2005 http://www.chem.umn.edu/ groups/arriaga/ Slide 10 Bowser Group Research Interests http://www.chem.umn.edu/groups/bowser/ NEUROSCIENCE APTAMERS 10-Second In Vivo Monitoring 10-Second In Vivo Monitoring Novel Neuromessengers Novel Neuromessengers Stroke Stroke Sensory Response Sensory Response New Sampling Methods New Sampling Methods Single Neuron Analysis Single Neuron Analysis Alternative Selection Methods Alternative Selection Methods (CE-SELEX) (CE-SELEX) Microfluidics Microfluidics Catalytic Aptamers Catalytic Aptamers Aptamer Assays (neuropeptides, bacteria, etc.) Aptamer Assays (neuropeptides, bacteria, etc.) Slide 11 Taton Group Research: Connecting Nanotech and Biotech Application Example: Nanoparticle labels for electrophoretic analysis of DNA DNA bands are visible with the naked eye. No staining necessary. Challenge: How to combine nano- objects and biological molecules? (cuvette of DNA-modified, polymer-coated nanoparticles) ~15 nm (Electron microscope image of polymer-coated nanoparticles) http://www.chem.umn.edu/groups/taton/ Slide 12 Computational Chemistry Slide 13 Christopher Cramer (*) Jiali Gao William Gleason Donald Truhlar Rick Wagner Darrin York Slide 14 Jiali Gao http://www.chem.umn.edu/groups/gao Computational Biology dynamics, pathways, and catalysis protein-membrane interactions macromolecular assembly Approach combined QM/MM methods MOVB Monte Carlo and molecular dynamics Slide 15 Bill Gleason - Chemical Biology Interests Biomolecular recognition (e.g. heparin/protein interactions, receptor kinases) Biomaterials - synthesis and properties of novel polymeric biomaterials Biomarker discovery for clinical applications Mohammaddi Structure FGF:Receptor:Heparin 2:2:2 http://ccgb.umn.edu/~bgleason/ Slide 16 CDCD CACA H Truhlar Research Group http://comp.chem.umn.edu/truhlar/ Slide 17 Density-functional calculations of biological reaction models Hybrid QM/MM simulations of reactions in RNA and in solution York Group: Density-functional theory and hybrid QM/MM methods http://riesling.chem.umn.edu/ Slide 18 Design & Synthesis Slide 19 George Barany Mark Distefano Craig Forsyth Larry Que Bill Tolman Rick Wagner Slide 20 What do Laundry, Poker, and Proteins have in common? Slide 21 Slide 22 A SYNTHETIC CHEMIST LOOKS AT PROTEIN FOLDING GB1 Prof. George Barany www.chem.umn.edu/ groups/baranygp/index.htm Slide 23 Distefano Research Group Organic and Protein Chemistry Cancer Catalysis Antibiotics Tissue Engineering http://www.chem.umn.edu/groups/distefano/ Slide 24 Forsyth Research Group PP1 - Okadaic Acid Docking Model V. A. Frydrychoski K. A. Plummer Slide 25 Biocatalysis Chemical Biology Nanobiotechnology C-69 H-107 D-122 Drug Design and Delivery -Antivirals -Antitumor -Carcinogen Activating Enzymes -Chemical Control of Protein Macrocyclization Wagner Research Group Interests Slide 26 Enzyme Chemistry Slide 27 Mark Distefano Craig Forsyth Jiali Gao John Lipscomb Karin Musier-Forsyth Larry Que Slide 28 Species-specific differences in tRNA and amino acid recognition Expanding the genetic code:Incorporation of unnatural amino acids Amino acid editing/proofreading http://www.chem.umn.edu/groups/musier-forsyth/ Slide 29 Larry Que: Spectroscopic studies of oxygen activating iron enzymes with a 2-His-1-carboxylate motif Enzymes catalyze hydrocarbon oxidations and antibiotic synthesis, degrade aromatic pollutants in soil, and sense hypoxia in cellsEnzymes catalyze hydrocarbon oxidations and antibiotic synthesis, degrade aromatic pollutants in soil, and sense hypoxia in cells Spectroscopic methods used include EPR, NMR, Raman and EXAFS. Rapid kinetics techniques are used to trap reactive intermediatesSpectroscopic methods used include EPR, NMR, Raman and EXAFS. Rapid kinetics techniques are used to trap reactive intermediates http://bioinorg.chem.umn.edu/quespace/ Slide 30 Structure & Spectroscopy Slide 31 John Lipscomb Karin Musier-Forsyth Larry Que Gianluigi Veglia Slide 32 http://www.chem.umn.edu/groups/veglia/ Slide 33 NMR Studies of Membrane Proteins. Veglia Group Solution NMRSolid-state NMR Slide 34 Nucleic Acids Slide 35 Victor Bloomfield Michael Bowser Karin Musier-Forsyth Andrew Taton Darrin York Slide 36 Solid-Phase RNA/DNA Synthesizer Slide 37 Human tRNA Lys primer selection RNA chaperone activity of HIV nucleocapsid protein Musier-Forsyth http://www.chem.umn.edu/groups/musier-forsyth/ Slide 38 Reaction Region QM active site + MM surrounding (Newtonian dynamics) Buffer Region (Langevin dynamics) External potential of solute and solvent Stochastic boundary York Group: Multi-scale Quantum Models for RNA catalysis http://riesling.chem.umn.edu/ Slide 39 Summary & Conclusions Chemical Biology: represents the happening interface for 21 st century research Come to University of Minnesota, and help put the fun into structure & function! http://www.chem.umn.edu/bio/