Transcript Document

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.
Chemical Biology
Specialty Area at U of M
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19 Faculty
Highly Interdisciplinary Research
NIH Chemistry and Biology Interface
Training Grant (CBITG)
Chemical Biology Colloquium
Laboratory Rotation Program
CBITG Areas of Training
Bioorganic
Chemistry
Nucleic Acid
Chemistry
Med
Chem
Metallobiochemistry
Chemistry
Biocatalysis &
Biomolecular Design
BMBB
Microbiology
Engineering
Metabolic Pathways
Single Cell/
Molecule Studies
Chemical Biology
Coursework at U of M
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Flexible program
Mechanisms of Chemical Reactions
Introduction to Chemical Biology
Chemical Biology of Enzymes
Nucleic Acids
Biochemistry
Optional courses (2)
Introduction to Graduate
Research: Chem 8025
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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
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Course Description
Rotate through two different laboratories. Each rotation
lasts approximately seven weeks, with one credit
earned for each rotation
Research Areas Represented among
Chemical Biology Faculty at U of M
• Bioanalytical & Biomaterials
• Computational Chemistry
• Design & Synthesis
• Enzyme Chemistry
• Structure & Spectroscopy
• Nucleic Acids
Bioanalytical
&
Biomaterials
 Edgar Arriaga
 Michael Bowser
 Marian Stankovich
 Andrew Taton
Subcellular
distribution
O
1
OH
11
12
C OC H2O H
10
9
2
OH
3
8
5
4
6
OC H3 O
7
OH
O
5'
H 3C
1'
O
3'
H
Doxorubicin
4'
OH
N H2
2'
1.2
Metabolites
Arriaga
Fluorescence (V)
1.0
0.8
0.6
Group, 2005
http://www.chem.umn.edu/
groups/arriaga/
0.4
0.2
100
150
200
Migration Time (s)
250
Bowser Group Research Interests
http://www.chem.umn.edu/groups/bowser/
APTAMERS
NEUROSCIENCE
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10-Second In Vivo Monitoring
Novel Neuromessengers
Stroke
Sensory Response
New Sampling Methods
Single Neuron Analysis
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Alternative Selection Methods
(CE-SELEX)
Microfluidics
Catalytic Aptamers
Aptamer Assays (neuropeptides,
bacteria, etc.)
Taton Group Research:
Connecting Nanotech and Biotech
http://www.chem.umn.edu/groups/taton/
Challenge: How to combine nanoobjects and biological molecules?
Application Example:
Nanoparticle labels for
electrophoretic analysis of DNA
(Electron microscope image of
polymer-coated nanoparticles)
(cuvette of DNA-modified,
polymer-coated nanoparticles)
DNA bands are visible with
the naked eye. No staining necessary.
Computational Chemistry
 Christopher Cramer (*)
 Jiali Gao
 William Gleason
 Donald Truhlar
Rick Wagner
 Darrin York
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
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
http://ccgb.umn.edu/~bgleason/
Mohammaddi Structure
FGF:Receptor:Heparin 2:2:2
Truhlar Research
Group
CA
H
CD
http://comp.chem.umn.edu/truhlar/
York Group: Density-functional theory and hybrid
QM/MM methods
Hybrid QM/MM
simulations of
reactions in RNA and
in solution
Density-functional
calculations of biological
reaction models
http://riesling.chem.umn.edu/
Design
&
Synthesis
 George
Barany
 Mark Distefano
 Craig Forsyth
Larry Que
 Bill Tolman
 Rick Wagner
Laundry
Poker
Proteins
What do Laundry, Poker, and Proteins have in common?
Laundry
Poker
Proteins
A SYNTHETIC
CHEMIST LOOKS AT
PROTEIN FOLDING
Prof. George Barany
www.chem.umn.edu/
groups/baranygp/index.htm
GB1
Distefano Research Group
Organic and Protein Chemistry
OH
• Cancer
N
N
4'
• Catalysis
5'
• Antibiotics
L38K
S
S
V60C
• Tissue Engineering
http://www.chem.umn.edu/groups/distefano/
Forsyth Research Group
PP1 - Okadaic Acid Docking Model
V. A. Frydrychoski
K. A. Plummer
Wagner Research Group Interests
Drug Design
and Delivery
Biocatalysis
C-69
Chemical
Biology
-Antivirals
-Antitumor
D-122
H-107
-Carcinogen
Activating
Enzymes
Nanobiotechnology
-Chemical Control of Protein Macrocyclization
Enzyme
Chemistry
Mark Distefano
Craig Forsyth
 Jiali Gao
 John Lipscomb
Karin Musier-Forsyth
 Larry Que
M usi er-F orsy th Lab
I. T ransla tion o f t h e G en et ic C od e
 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/
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 cells
• Spectroscopic methods
used include EPR,
NMR, Raman and
EXAFS. Rapid
kinetics techniques are
used to trap reactive
intermediates
http://bioinorg.chem.umn.edu/quespace/
Structure
&
Spectroscopy
 John Lipscomb
Karin Musier-Forsyth
Larry Que
Gianluigi Veglia
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
http://www.chem.umn.edu/groups/veglia/
NMR Studies of Membrane Proteins.
Veglia Group
Solution NMR
Solid-state NMR
Nucleic
Acids
 Victor Bloomfield
Michael Bowser
 Karin Musier-Forsyth
 Andrew Taton
 Darrin York
Solid-Phase RNA/DNA Synthesizer
Musier-Forsyth
II. RNA-Pr ote in In ter act ions in HI V
Human tRNALys
primer selection
RNA chaperone
activity of HIV
nucleocapsid protein
http://www.chem.umn.edu/groups/musier-forsyth/
York Group: Multi-scale Quantum Models for
RNA catalysis
External potential
of solute and
solvent
Stochastic
boundary
Reaction Region
QM active site +
MM surrounding
(Newtonian dynamics)
Buffer Region
(Langevin dynamics)
http://riesling.chem.umn.edu/
Summary & Conclusions
 Chemical Biology: represents
the “happening” interface for 21st
century research
 Come to University of
Minnesota, and help put the fun
into “structure & function”!
http://www.chem.umn.edu/bio/