This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The major Area I goals are to elucidate the structures and functions of biological molecules with the aim of understanding and explaining their functions in development and in cellular events. A major new initiative for the five-year renewal is to recruit a new faculty member in the area of X-ray diffraction for the determination of protein structure and to provide startup funds to equip this facility. Our request for the hire of an X-ray crystallographer is motivated by the need to complement and enhance the ongoing structural work carried out by NMR. We have also secured X-ray crystalography equipment which was donated by Novartis and set up through funds from the college in the new Pathways Bioinformatics and Biotechnology Center at CCNY. Recent developments in biochemistry and structural biology allow members of Area I to further expand their areas of study into large macromolecules and macromolecular assemblies. To be more productive and competitive, they must exploit the new technologies and turn to increased use of NMR techniques in conjunction with the NMR facilities that are integral to the New York City Structural Biology Center that officially opened on our campus December 16, 2002. In accord with this goal we have added a specialist in NMR spectroscopy, Dr. Ronnie Ghose, to Area I. This hire was approved by RCMI in our last grant renewal. He has developed an exciting independent research program and has secured extramural funding. He actively interacts with all members of Area I and members of other areas as well.Our equipment is continually being improved and up-dated. During the past year one 500 and one 600 MHz spectrometers were delivered and put into service on the Plaza Level of the Marshak Science Building. The cost for these machines was split between the College and the RCMI. This new capability expands the use of mass spectrometry further into large and fragile molecules and makes this tool available to researchers in the biological sciences.Barbara Zajc was hired with RCMI funds during the current grant period in the area of Bioorganic Chemistry. She studies DNA-carcinogen conjugates following the incorporation of fluorine as a modulator of biological activity and monitors structural changes that result form these modifications.Our central facility now has two Molecular Dynamics phosphoimagers and a Molecular Dynamics Laser Densitometer and these are of general utility to everyone in RCMI. Accomplishments of Area I Faculty and Research HighlightsA majority of the Area I faculty (Balogh-Nair, Ghose, Gunner, Lazaridis, Schulz, Tasayco, Zajc) are well funded by external grants. Dr. Schulz was invited to write a book chapter entitled 'Oxidation of Fatty Acids in Eukaryotes' and he serves on the Medical Biochemistry Study Section at the NIH. Dr. Gunner was honored with a Presidential Early Career Award for Scientists and Engineers (PECASE) with a $0.5 million grant. Summary of Faculty Research Dr. Balogh-Nair (Chemistry) is engaged in the synthesis of dendrimers with enhanced activities towards M-tropic HIV-1 viral strains. In contrast to traditional polymers, dendrimers are unique core-shell structures possessing three basic architectural components: (a) a core, (b) an interior of shells (generation) consisting of repetitive branch cell units, and (c) terminal functional groups, I.E., the outer shell or periphery. Dr. Ghose focuses on the development and implementation of novel NMR techniques to probe the structure and dynamics of biomolecules. He is also interested in deciphering the structure-function relationships in key enzymes involved in the Src-signaling pathway. He has recently published a paper in the J. of Biomolecular NMR on novel NMR methods that probe slow correlated motions in proteins. Dr. Gunner (Biophysics), an RCMI hire, is working to (a) develop tools to analyze and compare the energies of charged groups in proteins, (b) analyze the function of electron and proton where side chain or substrate ionization states are important for function, and (c) survey the protein structural data bank to identify motifs that stabilize buried charges. Dr. Lazaridis made a big step forward during the past year towards modeling of membrane proteins by developing an effective energy function for proteins in lipid bilayers as an extension of his EEF1 aqueous solution energy function. Dr. Schulz (Biochemistry) has a major goal to provide a detailed understanding of the reactions and auxiliary enzymes that are specifically required for the b-oxidation of unsaturated and hydroxy fatty acids. Dr. Tasayco (Biochemistry), an RCMI hire, produced a pioneering publication in Biochemistry using differential scanning calorimetry to recognize regions with residual structure in a family of complementary disordered protein fragments. She is currently studying the residual structure in the unfolded state of proteins by NMR spectroscopy to provide benchmarks for the prediction of protein energetics. Dr. Zajc studies the structure-activity relationships (SAR) in the area of chemical carcinogenesis. Specifically, she is addressing the SAR studies of DNA-carcinogen conjugates via site-specific incorporation of fluorine as a modulator of biological activity, to evaluate structural changes that occur upon such modifications.
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