Biochemistry, Biological Signaling Mechanisms and Global Proteomic Analysis

dratzchemistry.montana.edu

The Dratz lab uses global proteomic analysis to investigate signaling networks in cells and studies the structure and function of membrane receptor and amplifier proteins. The genome of an organism is quite static (apart from rare mutations), whereas the proteins expressed or modified by cells often change rapidly in response to stimuli. Functional proteomics is the study of the proteins that are up- or down-regulated, or change in post-translational modifications (PTMs), in response to biological or environmental stimuli. Proteins typically contain many different PTMs, which affect the protein’s activity, cellular localization, or protein partners. Proteomics technology uses mass spectrometers for protein identification and for characterization of PTMs, but first must rely on a variety of separation techniques such as 2D gels (e.g. Halligan, et al., Nucleic Acids Res. 2004;32: W638-44) or 2D liquid chromatography to separate complex protein or peptide mixtures before mass spectral analysis is feasible. We are developing novel, designer fluorescent dyes, in collaboration with Prof. Grieco's group, that enhance detection sensitivity, pinpoint posttranslational modifications, and monitor changes in enzyme activity in the proteome. We are applying this new proteomics technology for example, to finding new diagnostic tools for type 2 diabetes, to increased understanding of immune adjuvants, to better understanding neurodevelopment, and aging in mitochondria.

Prof. Dratz has a long standing interest in biochemical nutrition and is applying proteomic methods to gain deeper understanding of nutritional issues in collaboration with researchers in Plant Sciences. Proteomics is a major research frontier and there are abundant research opportunities in bioanalytical chemistry, biochemistry, molecular biology and collaborations in synthetic organic chemistry and cell biology.

The Dratz laboratory also has a long-standing interest in G protein-coupled receptor (GPCR) systems that are responsible for over half the signaling systems in biology. Chemokine GPCRs that are responsible for intercellular signaling in the immune system are also used as receptors for virus entry. We are studying agonist and antagonist binding mechanisms in two chemokine receptors CCR5 and CXCR4 that AIDS virus uses to gain entry to lymphocytes and where infection is blocked by agonists and antagonists. Approaches include antibody imprinting for protein structure determination, photochemical cross-linking of bioactive molecules to map out receptor binding sites, and protein and peptide mass spectrometry.

Selected Publications

Sands DC, Morris CE, Dratz EA, Pilgeram AL:
Elevating optimal human nutrition to a central goal of plant breeding and production of plant-based foods
Plant Science 177 (2009) 377–389

Piscitelli CL, Angel TE, Bailey BW, Hargrave P, Dratz EA, Lawrence CM. :
The equilibrium between metarhodopsin-I and metarhodopsin-II is dependent on the conformation of the 3rd cytoplasmic loop.
J Biol Chem. 2005 Dec 29

Riesselman M, Miettinen HM, Gripentrog JM, Lord CI, Mumey B, Dratz EA, Stie J,Taylor RM, Jesaitis AJ.:
C-terminal tail phosphorylation of N-formyl peptide receptor: differential recognition of two neutrophil chemoattractant receptors by monoclonal antibodies NFPR1 and NFPR2.
J Immunol. 179(4):2520-31, (2007).

Halligan BD, Ruotti V, Jin W, Laffoon S, Twigger SN, Dratz EA. :
ProMoST (Protein Modification Screening Tool): a web-based tool for mapping protein modifications on two-dimensional gels.
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W638-44.

Barry RC, Alsaker BL, Robison-Cox JF, Dratz EA. :
Quantitative evaluation of sample application methods for semipreparative separations of basic proteins by two-dimensional gel electrophoresis.
Electrophoresis. 2003 Oct;24(19-20):3390-404.

Keywords:
Proteomics, Protein Chemistry, Chemical Biology