Areas of Interest
The term Proteome refers to the complement of proteins that are expressed by an organism at any particular instant or set of experimental conditions. It is a goal of proteomics to be able to discover the identity of these gene products for whole genomes in a timely manner.
Our laboratory is very interested in understanding the functional and organizational patterns underlying complex systems, i.e. to relate the proteome to the genome.
A major focus has been the development of new technologies for comprehensive analysis of the responses of living cells to their environment at the molecular level, e.g. linking protein structure information to genome sequence. Thus a goal has been to achieve ultra-high throughput analysis of the majority of the proteins present in cells. Several recent breakthroughs have made this new technology feasible. These include the development of the Delayed Extraction technology for matrix assisted laser desorption mass spectrometry (MALDI), database search algorithms using mass mapping information, and techniques we've developed for MALDI mass mapping directly from thin layer electrophoresis gels.
These three methodologies together provide the potential for high-throughput, automated identification, and characterization of proteins from complex mixtures, providing a direct link between the structural information in the gene sequence databases with the functional information inherent in 2-D gels of cellular proteins. The first application of this technology is the development of "virtual gel" images (3-D gel images) of small genome organisms based on MALDI scans of isoelectric focusing gel separations of whole cell extracts. These gel images have the dimensions of pI, mass, and ion intensity. This technique will be particularly useful in the post-genome era and is also a research tool of immediate utility to many investigators.
Much of our work is centered around the characterization of proteins separated by 2D gel electrophoresis. This technique refers to the separation of proteins in the first dimension by isoelectric focusing in a polyacrylamide immobilized pH gradient(IPG) gel followed by a second-dimension separation on SDS polyacrylamide gels. We are using several forms of post-separation analyses such as mass spectrometry and Edman sequencing to identify proteins on 2D gels.
Other projects include development of new separation technologies for analysis of membrane proteins, high loading separation methods compatible with electrospray MS, and computational tools for analysis and management of large amounts of heterogeneous proteome information.
PRIME: Proteome Research Information Management Environment
Proteome mapping projects generate large amounts of complex, hierarchical data. The intent of PRIME is to capture and organize data generated by these research efforts and to present the results of such analyses to users in an organized and intuitive way. The system allows researchers to track and store data, acting as a central repository for relevant data generated by various groups as well as providing meaningful views of the collective research efforts for a particular project.
Hye Kyong Kweon, Postdoctoral Fellow
Angela Walker, Research Laboratory Specialist
Mark Gjukich, Web Content Administrator
Honors & Awards
1993 Alan McCall Award in Mass Spectrometry for best paper in journal Organic Mass Spectrometry
1998 Inventor Recognition University of Michigan Technology Management office
1998 Faculty Recognition Award
Our research is funded through the generosity of The National Cancer Institute, The National Human Genome Research Institute, and The Merck Genome Research Institute. Please visit http://www.proteome.med.umich.edu
1. Falkner J, Andrews P. Fast tandem mass spectra-based protein identification regardless of the number of spectra or potential modifications examined. Bioinformatics. 2005 May 15; 21(10):2177-84. Ulintz PJ, Zhu J, Qin ZS, Andrews PC. Improved classification of mass spectrometry database search results using newer machine learning approaches. Mol Cell Proteomics. 2006 Mar;5(3):497-509. Epub 2005 Nov 30.
2. Falkner JA, Falkner JW, Andrews PC. ProteomeCommons.org JAF: reference information and tools for proteomics. Bioinformatics. 2006 Mar 1;22(5):632-3. Epub 2006 Jan 24.
3. Ostrom, PH, Gandhi, H, Strahler, JR, Walker, AK, Andrews, PC, Leykam, J, Stafford, TW, Kelly, RK, Walker, DN, Buckley, M and Humpula,J.: Unraveling the sequence and structure of the protein osteocalcin from a 42 ka fossil horse. Geochimica et Cosmochimica Acta. (in press)
4. Garcia BA, Joshi S, Thomas CE, Chitta RK, Diaz RL, Busby SA, Andrews PC, Ogorzalek Loo RR, Shabanowitz J, Kelleher NL, Mizzen CA, Allis CD, Hunt DF. Comprehensive Phosphoprotein Analysis of Linker Histone H1 from Tetrahymena thermophila.Mol Cell Proteomics. 2006 Sep;5(9):1593-1609. Epub 2006 Jul 10.
5. Ulintz PJ, Zhu J, Qin ZS, Andrews PC. Improved classification of mass spectrometry database search results using newer machine learning approaches. Mol Cell Proteomics. 2006 Mar;5(3):497-509. Epub 2005 Nov 30.
6. Jagtap P, Michailidis G, Zielke R, Walker AK, Patel N, Strahler JR, Driks A, Andrews PC, Maddock JR. Early events of Bacillus anthracis germination identified by time-course quantitative proteomics.
Proteomics. 2006 Aug 23; [Epub ahead of print]
7. Jiang M, Datta K, Walker A, Strahler J, Bagamasbad P, Andrews PC, Maddock JR. The Escherichia coli GTPase CgtAE Is Involved in Late Steps of Large Ribosome Assembly. J Bacteriol. 2006 Oct;188(19):6757-70.
8. Kozarova A, Sliskovic I, Mutus B, Vacratsis PO, Simon ES, Andrews PC. Identification of Redox Sensitive Thiols of Protein Disulfide Isomerase Using Isotope Coded Affinity Technology and Mass Spectrometry. J Am Soc Mass Spectrom. 2006 Oct 27; [Epub ahead of print]
9. Falkner JA, Falkner JW, Andrews PC. ProteomeCommons.org IO Framework: reading and writing multiple proteomics data formats. Bioinformatics. 2007 Jan 15;23(2):262-3.
10. Falkner JA, Kachman M, Veine DM, Walker A, Strahler JR, Andrews PC. Validated MALDI-TOF/TOF Mass Spectra for Protein Standards. J Am Soc Mass Spectrom. 2007 May;18(5):850-5. PMID: 17329120
11. Jiang M, Sullivan SM, Walker AK, Strahler JR, Andrews PC, Maddock JR. Identification of novel Escherichia coli ribosome-associated proteins using isobaric tags and multidimensional protein identification techniques. J Bacteriol. 2007 May;189(9):3434-44. PMID: 17337586
12. Jayapandian M, Chapman A, Tarcea VG, Yu C, Elkiss A, Ianni A, Liu B, Nandi A, Santos C, Andrews P, Athey B, States D, Jagadish HV. Michigan Molecular Interactions (MiMI): putting the jigsaw puzzle together. Nucleic Acids Res. 2007 Jan;35(Database issue):D566-71. Epub 2006 Nov 27.
13. Parrish JR, Yu J, Liu G, Hines JA, Chan JE, Mangiola BA, Zhang H, Pacifico S, Fotouhi F, Dirita VJ, Ideker T, Andrews P, Finley RL Jr. A proteome-wide protein interaction map for Campylobacter jejuni. Genome Biol. 2007 Jul 5;8(7):R130
14. Mathivanan S, et al. Human Proteinpedia enables sharing of human protein data. Nat Biotechnol. 2008 Feb;26(2):164-7. PMID: 18259167
15. Leichert LI, Gehrke F, Gudiseva HV, Blackwell T, Ilbert M, Walker AK, Strahler JR, Andrews PC, Jakob U. Quantifying changes in the thiol redox proteome upon oxidative stress in vivo. Proc Natl Acad Sci U S A. 2008 Feb 14; [Epub ahead of print] PMID: 18287020
16. Ulintz PJ, Bodenmiller B, Andrews PC, Aebersold R, Nesvizhskii AI. Investigating MS2/MS3 matching statistics: a model for coupling consecutive stage mass spectrometry data for increased peptide identification confidence. Mol Cell Proteomics. 2008 Jan;7(1):71-87. Epub 2007 Sep 13. PMID: 17872894