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dc.titleUsing Comepensation-Attenuated Genetics to Understand Underlying Networks Governing Cellular Robustness
dc.contributor.authorWANG SIHUI
dc.identifier.citationWANG SIHUI (2013-08-16). Using Comepensation-Attenuated Genetics to Understand Underlying Networks Governing Cellular Robustness. ScholarBank@NUS Repository.
dc.description.abstractThe unfolded protein response (UPR) is a homeostatic mechanism in cells which helps restore equilibrium in the endoplasmic reticulum (ER) in the event of ER stress. Using compensation-attenuated genetics, a novel allele of protein disulfide isomerase (PDI), pdi1-2, was isolated. Pdi1p is an essential protein in Saccharomyces cerevisiae involved in the catalytic redox and isomerization of disulfide bonds in secretory and cell-surface proteins. pdi1-2 is completely inviable in the absence of the UPR, but UPR activation suppressed lethality and compensated for defects in bioprocessing of endogenous proteins, CPY and Gas1p. Microarray analysis suggested that the UPR is modulated in response to different physiological stresses. In pdi1-2, upregulation of the Hsp70 chaperone Kar2p and its Hsp40 cofactors helped buffer the lethal PDI1 dysfunction, whereas other PDI family members were dispensable. This suggests that different chaperone networks in the ER work in synergy to contribute to cellular robustness.
dc.subjectyeast genetics, unfolded protein response, robustness, PDI1, KAR2, chaperone
dc.contributor.departmentNUS GRAD SCH FOR INTEGRATIVE SCI & ENGG
dc.contributor.supervisorDAVIS NG TAI WAI
dc.description.degreeconferredDOCTOR OF PHILOSOPHY
Appears in Collections:Ph.D Theses (Open)

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