Associate Director of Proteomics
Ansgar Brock, Ph.D.
Senior Research Investigator I
Biology in the post-genomic era is marked by the desire to study cells, cellular processes, and diseases at the protein level. One of the most powerful tools to do this is mass spectrometry, which has rapidly become an indispensable technique for the characterization of biological macromolecules. Besides our support of GNF's discovery efforts, our resources and services of identification, quantitation, and structural characterization are also provided to programs such as the Joint Center for Structural Genomics. In addition, we work with numerous academic collaborators.
Not everything can be solved with existing tools, however, and the desire to analyze highly dynamic protein networks of ever increasing complexity necessitates the continual development of ever more sophisticated analysis methods. Therefore, in our technology research, we develop new instrumentation and analysis methodologies.
Discovery Programs Support
At GNF, we are active in all aspects of protein analysis by mass spectrometry. We perform state-of-the-art analyses in support of the entire biological discovery and drug development efforts within GNF and contribute to collaborative programs. Applications include:
Assessing the quality of all proteins produced and/or utilized at GNF
Obtaining detailed characterization of specific protein samples, including information on post-translational modifications, differential proteolytic processing, the effective incorporation of unnatural amino acids etc.
- Structural characterization of proteins by hydrogen/deuterium exchange mass spectrometry in collaboration with JCSG
- Identifying unknown protein species of biological interest isolated by classical biochemical methods, including the determination of novel protein-protein, protein-nucleic acid, or protein-small molecule interactions/ complexes. Figure 1 below illustrates the basic methodology employed for such studies.
Mass Spectrometry Technology Research
Despite the power of modern mass spectrometry techniques, the types of questions that our scientists are beginning to ask offer numerous challenges that simply cannot be met using current instrumentation and methodologies. Describing the nature of highly complex and ever changing proteomes of living systems, for instance, is a problem of a vast scale. Accordingly, we perform applied research in numerous disciplines focused ultimately on expanding the ability of mass spectrometry to drive biological discovery. Several of our discoveries have been licensed and commercialized by proteomics vendors. Our research includes:
The discovery and implementation of enrichment schemes targeting specific chemical functionalities, such as the selective enrichment and characterization of protein phosphorylation in order to elucidate signaling pathways. Figure 2 below illustrates another methodology for the enrichment and analysis of O-GlcNAc modified species.
The development of labeling reagents to affect relative ionization efficiencies, tandem MS fragmentation pathways, and/or differential quantitation
The implementation of highly sensitive, time efficient analysis schemes based on LC-MALDI MS and MS/MS
The design and utilization of instrumentation that both consistently enables and effectively exploits high mass measurement accuracies
- Lemke EA, Summerer D, Geierstanger BH, Brittain SM, Schultz PG. Control of protein phosphorylation with a genetically encoded photocaged amino acid. Nat Chem Biol 2007;3(12):769-72.
- Khidekel N, Ficarro SB, Clark PM, Bryan MC, Swaney DL, Rexach JE, Sun YE, Coon JJ, Peters EC, Hsieh-Wilson LC. Probing the dynamics of O-GlcNAc glycosylation in the brain using quantitative proteomics. Nat Chem Biol 2007;3(6):339-48.
- Chen S, Takanashi S, Zhang Q, Xiong W, Zhu S, Peters EC, Ding S, Schultz PG. Reversine increases the plasticity of lineage-committed mammalian cells. Proc Natl Acad Sci U S A 2007;104(25):10482-7.
- Liu W, Brock A, Chen S, Chen S, Schultz PG. Genetic incorporation of unnatural amino acids into proteins in mammalian cells. Nat Methods 2007;4(3):239-44.