Browsing by Author "Rende, Deniz."

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    Development of a systems based modular approach to link complex diseases
    (Thesis (Ph.D.)-Bogazici University. Institute for Graduate Studies in Science and Engineering, 2010., 2010.) Rende, Deniz.; Kırdar, Betül.
    A novel systems based modular approach was developed in this study to investigate the shared underlying mechanisms of three prevalent complex disorders: cardiovascular disease (CVD), Type 2 diabetes (T2D) and Alzheimer‘s disease (AD). The disease related functional linkage networks were constructed and analyzed in every aspects of modularization. The fundamental biological processes were deciphered through integration of various levels of "omics" data. The identification of the links between these diseases was accomplished through the shared proteins and biological processes. The cardiovascular disease functional linkage network (CFN) containing 1536 proteins and 3345 linkages was constructed using proteins encoded by 234 genes associated with cardiovascular disease. The modular architecture of this network and its integration with "bibliomics" indicated that blood coagulation, lipid metabolism and renin-angiotensin systems were found to be linked to CVD as expected. The modularization in CFN was anticipated to exert a potential to develop a general perspective, hence the functional modules enumerated from CFN were evaluated in terms of shared pathways, co-localization, co-expression and associations with diseases. The members of the top scoring functional modules were assembled in a condensed network representing the fundamental biological processes. The approach was later applied to the other two complex disorders. The functional linkage networks include 2734 proteins / 14823 linkages (TDFN) and 1587 proteins / 7785 linkages (ADFN) for Type 2 diabetes and Alzheimer‘s disease, respectively. The individual fundamental processes and signalling cascades observed in each of these diseases are converged at blood coagulation, glucose homeostasis, lipid metabolism, oxidative stress and inflammation. The central roles of the proteins generating inflammatory response in all disease networks indicate that inflammation might be the missing link between CVD, T2D and AD.
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    Production of cystic fibrosis transmembrane conductance regulator (CFTR) protein in recombinant cells
    (Thesis (M.S.)-Bogazici University. Institute for Graduate Studies in Science and Engineering, 2004., 2004.) Rende, Deniz.; Kırdar, Betül.
    The application of the recombinant DNA technology is essential for the large scale production of therapeutic proteins and for the elucidation of their structures and function. Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is an important protein with a possible therapeutical function. In this study, the CFTR gene was cloned into the pYES2 plasmid vector and expressed in Saccharomyces cerevisiae AS102 cells, in which cell lysis was controlled by pMET-regulation cassette.Within the framework of this thesis, the CFTR gene was isolated from pBQ6.2 plasmid vector, and was cloned into the pYES2 plasmid vector under the GAL1 promoter. Two colonies harboring the recombinant plasmid construct containing the CFTR gene insert in correct orientation, namely p57 and p312, were identified by the restriction enzyme analysis. These plasmids were then transformed with Saccharomyces cerevisiae AS102 cells. CFTR protein was found to be expressed when the protein content of the cellular extracts was analyzed by SDS-Polyacrylamide Gel Electrophoresis. Analysis of medium at different time intervals showed an increase in protein concentrations of medium upon methionine addition, by repression of the expression of pMET-regulation cassette, thus confirmed the release of proteins into the culture medium as a result of induced lysis.