c p f m chemical proteomics facility at marquette
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Internet2: Enabling Post-Genomic Technology at Marquette. C P F M Chemical Proteomics Facility at Marquette. The post-genomic challenge Exploring function across protein families using chemical probes. Basic research. Applied research. - PowerPoint PPT PresentationTRANSCRIPT
C P F MC P F M
Chemical Chemical Proteomics Proteomics
Facility at Facility at MarquetteMarquette
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- Marquette (Biology & Chemistry)- UW-Milwaukee (MFBSC)- UW-Madison (NMRFAM)
Long term goal: “Science in Service to Society”
Internet2: Enabling Post-Genomic Technology at Marquette
Applied research
Basicresearch
Internet2: Turning the CPFM into a Collaboratorium
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 Promise of Genomics: not yet realized …
“The human genome is data not knowledge, and will be useless until we understand what it means.” attributed to Sydney Brenner
Genes => Proteins
C P F MC P F M
Chemical Chemical Proteomics Proteomics
Facility at Facility at MarquetteMarquette
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
Beowulf/Linux cluster facility Modelling lab: remote access to NMRFAM
NMR spectrometer lab Fluorescence assay lab
CPFM Resources at Marquette:
Equipment
C P F MC P F M
Chemical Chemical Proteomics Proteomics
Facility at Facility at MarquetteMarquette
The post-genomic challenge Exploring function across protein families using chemical probes
Internet2: The CPFM as a Collaboratorium
Chemistry Biology
I2 I2
I2
1) Need High Speed (I2) Connection to MFBSC
Viewing of microscopy results at CPFM (imaging)
CPFM Client
I2
Fluorescence imaging as a window to:a) Zebrafish developmental biologyb) Drug transport
Zebrafish Estrogen Receptors (endocrine disruptor targets)
Computationally derived with homology modeling
Estrogen receptor… is a protein targeted by endocrinedisruptor pollutants (EPA regulations)
2) Need High Speed (I2) Connection to NMRFAM
CPFM Client
I2I2
Milo Westler, Ph.D.Operations Director
NMRFAM
Teleconference to NMRFAM: what is NMRFAM?
Computational Docking for Drug Design
(Dock, Autodock, Caveat & Grid)
HIV Protease inhibitor
Can use protein structure to design better drugs
And to avoid drug metabolism:-Toxic side effects-Drug/drug interactions
University of Texas at Austin
National Partnership for Advanced Computational Infrastructure
IBM Power 4 system
3) Need High Speed (I2) Connection to UTA
Marquette’s Beowulf cluster
CPFM Client
- Ligand-protein docking- Homology modeling- Chemoinformatic analysis of drug properties
I2I2
Fragments
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Molecular Legos?
Unique enabling of Chemoinformatics at Marquette
Summary
C P F MC P F M
Chemical Chemical Proteomics Proteomics
Facility at Facility at MarquetteMarquette
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)