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Internet2: Enabling Post-Genomic Technology at Marquette
CPFM
Chemical Proteomics
Facility at Marquette
The post-genomic challenge
Exploring function across protein
families using chemical probes
 The CPFM is in early stages of development
 Projects focus on studies of protein function (applied genomics)
 Participants from:
- MCW
Basic
Applied
research
research
- Marquette (Biology & Chemistry)
- UW-Milwaukee (MFBSC)
- UW-Madison (NMRFAM)
Long term goal: “Science in Service to Society”
Internet2: Turning the CPFM into a Collaboratorium
The Promise of Genomics: not yet realized …
Genes => Proteins
Potential Benefits:
- Better understanding of biology
- Pharmacogenomics & personalized medicine
- Treatments for currently untreatable disease
- Drugs with fewer side effects
- Better understanding of toxicology of pollutants
“The human genome is data not knowledge, and will be useless until we understand what it means.”
attributed to Sydney Brenner
CPFM
Chemical Proteomics
Facility at Marquette
The post-genomic challenge
Exploring function across protein
families using chemical probes
What is the Chemical Proteomics Facility at Marquette?
Resources (equipment, software) and people
With a mission to:
 Enable Chemical Proteomic studies of protein-ligand interactions
 Facilitate collaboration across departments and institutions
 Provide a better understanding of basic biology
 Use science to address social needs
 Train scientists and entrepreneurs with social conscience
S3 = Biotechnology with social conscience: science, business, law and engineering
CPFM
Chemical Proteomics
Facility at Marquette
The post-genomic challenge
CPFM Resources
at Marquette:
Equipment
Exploring function across protein
families using chemical probes
Beowulf/Linux cluster facility Modelling lab: remote access to NMRFAM
NMR spectrometer lab
Fluorescence assay lab
Internet2: The CPFM as a Collaboratorium
I2
Chemistry
I2
Biology
I2
1) Need High Speed (I2) Connection to MFBSC
CPFM Client
I2
Viewing of
microscopy results
at CPFM (imaging)
Fluorescence imaging as a window to:
a) Zebrafish developmental biology
b) Drug transport
Zebrafish Estrogen Receptors (endocrine disruptor targets)
Computationally derived with homology modeling
Estrogen receptor
… is a protein targeted by endocrine
disruptor pollutants (EPA regulations)
2) Need High Speed (I2) Connection to NMRFAM
CPFM Client
I2
Teleconference to NMRFAM: what is NMRFAM?
Milo Westler, Ph.D.
Operations Director
NMRFAM
Can use protein structure to design better drugs
Computational Docking for Drug Design
(Dock, Autodock, Caveat & Grid)
HIV Protease
inhibitor
And to avoid drug metabolism:
-Toxic side effects
-Drug/drug interactions
3) Need High Speed (I2) Connection to UTA
CPFM Client
University of Texas at Austin
I2
National Partnership for Advanced
Computational Infrastructure
- Ligand-protein docking
- Homology modeling
- Chemoinformatic analysis
of drug properties
IBM Power 4 system
Marquette’s Beowulf cluster
Unique enabling of Chemoinformatics at Marquette
Fragments
9
5
1
N
N
N
2
10
6
N
N
N
S
N
N+
O-
3
O
7
11
N
N
N
O
8
4
12
O
N
O
O
N
O
Molecular Legos?
CPFM
Chemical Proteomics
Facility at Marquette
Summary
The post-genomic challenge
Exploring function across protein
families using chemical probes
Internet2: Enabling remote access & collaboration
 NMRFAM and MFBSC facilities
 Computational resources (UT-Austin; Marquette)
 Access to local computational data & tools (chemoinformatics)
Databases: endocrine disruptors; optimized drug building blocks
S3: better drugs, better pollutant screening, basic Biology
Current CPFM Projects and Participants
Medical College of Wisconsin
- Henry Miziorko: Enzymes in the mevalonate biosynthetic pathway: structural and mechanistic studies
- Jung-Ja Kim: Structural characterization of molecular motion in NADPH-cytochrome P450 oxidoreducatase
Marquette: Chemistry
- James Kincaid: Complementary use of NMR & Raman studies to probe substrate binding to cytochrome P450
- Dan Sem: Probing protein-ligand interactions in toxicology and chemical proteomics: methods and application
Marquette: Biology
- Pinfen Yang: Mechanism of flagellar radial spoke: ligand binding and structural studies of radial spoke protein 2
- Rosemary Stuart: Role of Su e in oligomerizing the F1-F0 ATP synthase complex: structural and binding studies
Other collaborators and resources:
 UW-Milwaukee: Marine and Freshwater Biomedical Sciences Center
 UW-Madison: NMR Facility
 UT-Austin: Supercomputer Facility (NSF)