Researcher:
Ergin, Billur Çelebi

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Billur Çelebi

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Ergin

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Ergin, Billur Çelebi

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2012 - 201912020 - 20222

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    A strategy based on protein-protein interface motifs may help in identifying drug off-targets
    (American Chemical Society (ACS), 2012) Nussinov, Ruth; Department of Chemical and Biological Engineering; Department of Computer Engineering; Keskin, Özlem; Gürsoy, Attila; Ergin, Billur Çelebi; Faculty Member; Faculty Member; Teaching Faculty; Department of Chemical and Biological Engineering; Department of Computer Engineering; The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; College of Engineering; 26605; 8745; 261792
    Networks are increasingly used to study the impact of drugs at the systems level. From the algorithmic standpoint, a drug can "attack" nodes or edges of a protein-protein interaction network In this work, we propose a new network strategy, "The Interface Attack", based on protein-protein interfaces. Similar interface architectures can occur between unrelated proteins. Consequently, in principle, a drug that binds to one has a certain probability of binding to others. The interface attack strategy simultaneously removes from the network all interactions that consist of similar interface motifs. This strategy is inspired by network pharmacology and allows inferring potential off-targets. We introduce a network model that we call "Protein Interface and Interaction Network (P2IN)", which is the integration of protein-protein interface structures and protein interaction networks. This interface based, network organization clarifies which protein pairs have structurally similar interfaces and which proteins may compete to bind the same surface region. We built the P2IN with the p53 signaling network and performed network robustness analysis. We show that (1) "hitting" frequent interfaces (a set of edges distributed around the network) might be as destructive as eleminating high degree proteins (hub nodes), (2) frequent interfaces are not always topologically critical elements in the network, and (3) interface attack may reveal functional changes in the system better than the attack of single proteins. In the off target detection case study, we found that drugs blocking the interface between CDK6 and CDKN2D may also affect the interaction between CDK4 and CDKN2D.
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    Impact of ocean carbonation on long-term regulation of light harvesting in eelgrass Zostera marina
    (Inter-Research, 2021) Zimmerman, Richard C.; Hill, Victoria J.; Department of Molecular Biology and Genetics; Ergin, Billur Çelebi; Teaching Faculty; Department of Molecular Biology and Genetics; College of Sciences; 261792
    Seagrasses account for approximately 10% of the total carbon stored in the ocean, although photosynthesis of seagrasses is carbon-limited at present oceanic pH levels. Therefore, increasing atmospheric CO2 concentration, which results in ocean acidification/carbonation, is predicted to have a positive impact on seagrass productivity. Previous studies have confirmed the positive influence of increasing CO2 on photosynthesis and survival of the temperate eelgrass Zostera marina, but the acclimation of photoprotective mechanisms in this context has not been characterized. We aimed to quantify the long-term impacts of ocean acidification on photochemical control mechanisms that promote photosynthesis while simultaneously protecting eelgrass from photodamage. Eelgrass were grown in controlled outdoor aquaria at different aqueous CO2 concentrations ranging from similar to 50 to similar to 2100 mu M from May 2013 to October 2014 and examined for differences in leaf optical properties. Even with daily and seasonal variations of temperature and light, CO2 enrichment consistently increased plant size, leaf thickness and chlorophyll use efficiency, and decreased pigment content and the package effect while maintaining similar lightharvesting efficiency. These acclimation responses suggest that a common photosynthetic sensory function, such as redox regulation, can be manipulated by COCO(2)2 availability, as well as light, and may serve to optimize photosynthetic carbon gain by seagrasses into the Anthropocene.
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    Photorespiration in eelgrass (Zostera marina L.): a photoprotection mechanism for survival in a CO2-limited world
    (Frontiers, 2022) Zimmerman, Richard C. C.; Hill, Victoria J. J.; Department of Molecular Biology and Genetics; Ergin, Billur Çelebi; Teaching Faculty; Department of Molecular Biology and Genetics; College of Sciences; 261792
    Photorespiration, commonly viewed as a loss in photosynthetic productivity of C3 plants, is expected to decline with increasing atmospheric CO2, even though photorespiration plays an important role in the oxidative stress responses. This study aimed to quantify the role of photorespiration and alternative photoprotection mechanisms in Zostera marina L. (eelgrass), a carbon-limited marine C3 plant, in response to ocean acidification. Plants were grown in controlled outdoor aquaria at different [CO2]aq ranging from ~55 (ambient) to ~2121 ?M for 13 months and compared for differences in leaf photochemistry by simultaneous measurements of O2 flux and variable fluorescence. At ambient [CO2], photosynthesis was carbon limited and the excess photon absorption was diverted both to photorespiration and non-photochemical quenching (NPQ). The dynamic range of NPQ regulation in ambient grown plants, in response to instantaneous changes in [CO2]aq, suggested considerable tolerance for fluctuating environmental conditions. However, 60 to 80% of maximum photosynthetic capacity of ambient plants was diverted to photorespiration resulting in limited carbon fixation. The photosynthesis to respiration ratio (PE : RD) of ambient grown plants increased 6-fold when measured under high CO2 because photorespiration was virtually suppressed. Plants acclimated to high CO2 maintained 4-fold higher PE : RD than ambient grown plants as a result of a 60% reduction in photorespiration. The O2 production efficiency per unit chlorophyll was not affected by the CO2 environment in which the plants were grown. Yet, CO2 enrichment decreased the light level to initiate NPQ activity and downregulated the biomass specific pigment content by 50% and area specific pigment content by 30%. Thus, phenotypic acclimation to ocean carbonation in eelgrass, indicating the coupling between the regulation of photosynthetic structure and metabolic carbon demands, involved the downregulation of light harvesting by the photosynthetic apparatus, a reduction in the role of photorespiration and an increase in the role of NPQ in photoprotection. The quasi-mechanistic model developed in this study permits integration of photosynthetic and morphological acclimation to ocean carbonation into seagrass productivity models, by adjusting the limits of the photosynthetic parameters based on substrate availability and physiological capacity.