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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.

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Presentation on theme: "Chemical Biology Specialty Area at U of M Our program emphasizes highly interdisciplinary research and training, aimed at the development and integration."— Presentation transcript:

1 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.

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

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

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)

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 faculty’s lab  Course Description Rotate through two different laboratories. Each rotation lasts approximately seven weeks, with one credit earned for each rotation

6 Research Areas Represented among Chemical Biology Faculty at U of M Bioanalytical & Biomaterials Computational Chemistry Design & Synthesis Enzyme Chemistry Structure & Spectroscopy Nucleic Acids

7 Bioanalytical & Biomaterials

8  Edgar Arriaga  Michael Bowser  Marian Stankovich  Andrew Taton

9 Subcellular distribution Fluorescence (V) Migration Time (s) Doxorubicin Metabolites Arriaga Group, groups/arriaga/

10 Bowser Group Research Interests 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.)

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)

12 Computational Chemistry

13  Christopher Cramer (*)  Jiali Gao  William Gleason  Donald Truhlar  Rick Wagner  Darrin York

14 Jiali Gao Computational Biology dynamics, pathways, and catalysis protein-membrane interactions macromolecular assembly Approach combined QM/MM methods MOVB Monte Carlo and molecular dynamics

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

16 CDCD CACA H Truhlar Research Group

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

18 Design & Synthesis

19  George Barany  Mark Distefano  Craig Forsyth  Larry Que  Bill Tolman  Rick Wagner

20 What do Laundry, Poker, and Proteins have in common?

21

22 A SYNTHETIC CHEMIST LOOKS AT PROTEIN FOLDING GB1 Prof. George Barany groups/baranygp/index.htm

23 Distefano Research Group Organic and Protein Chemistry Cancer Catalysis Antibiotics Tissue Engineering

24 Forsyth Research Group PP1 - Okadaic Acid Docking Model V. A. Frydrychoski K. A. Plummer

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

26 Enzyme Chemistry

27  Mark Distefano  Craig Forsyth  Jiali Gao  John Lipscomb  Karin Musier-Forsyth  Larry Que

28  Species-specific differences in tRNA and amino acid recognition  Expanding the genetic code:Incorporation of unnatural amino acids  Amino acid editing/proofreading

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

30 Structure & Spectroscopy

31  John Lipscomb  Karin Musier-Forsyth  Larry Que  Gianluigi Veglia

32

33 NMR Studies of Membrane Proteins. Veglia Group Solution NMRSolid-state NMR

34 Nucleic Acids

35  Victor Bloomfield  Michael Bowser  Karin Musier-Forsyth  Andrew Taton  Darrin York

36 Solid-Phase RNA/DNA Synthesizer

37  Human tRNA Lys primer selection  RNA chaperone activity of HIV nucleocapsid protein Musier-Forsyth

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

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”!


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