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Publication Metadata only 3D printed kombucha biomaterial as a tissue scaffold and L929 cell cytotoxicity assay(Wiley, 2024) Yanbakan, Edaguel; Tuncel, Tugba; Kocak Sezgin, Ayse; Bozoglan, Emirhan; Berikten, Derya; Kar, Fatih; Department of Molecular Biology and Genetics; Bağlan, İlkyaz; Department of Molecular Biology and Genetics; College of SciencesTissue engineering includes the construction of tissue-organ scaffold. The advantage of three-dimensional scaffolds over two-dimensional scaffolds is that they provide homeostasis for a longer time. The microbial community in Symbiotic culture of bacteria and yeast (SCOBY) can be a source for kombucha (kombu tea) production. In this study, it was aimed to investigate the usage of SCOBY, which produces bacterial cellulose, as a biomaterial and 3D scaffold material. 3D printable biomaterial was obtained by partial hydrolysis of oolong tea and black tea kombucha biofilms. In order to investigate the usage of 3D kombucha biomaterial as a tissue scaffold, "L929 cell line 3D cell culture" was created and cell viability was tested in the biomaterial. At the end of the 21st day, black tea showed 51% and oolong tea 73% viability. The cytotoxicity of the materials prepared by lyophilizing oolong and black tea kombucha beverages in fibroblast cell culture was determined. Black tea IC50 value: 7.53 mg, oolong tea IC50 value is found as 6.05 mg. Fibroblast viability in 3D biomaterial + lyophilized oolong and black tea kombucha beverages, which were created using the amounts determined to these values, were investigated by cell culture Fibroblasts in lyophilized and 3D biomaterial showed viability of 58% in black tea and 78% in oolong tea at the end of the 7th day. In SEM analysis, it was concluded that fibroblast cells created adhesion to the biomaterial. 3D biomaterial from kombucha mushroom culture can be used as tissue scaffold and biomaterial.Publication Metadata only A brief atlas of insulin(Bentham Science, 2022) N/A; Department of Molecular Biology and Genetics; Ayan, Esra; Demirci, Hasan; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Koç Üniversitesi İş Bankası Yapay Zeka Uygulama ve Araştırma Merkezi (KUIS AI)/ Koç University İş Bank Artificial Intelligence Center (KUIS AI); Graduate School of Sciences and Engineering; College of Sciences; N/A; 307350Insulin is an essential factor for mammalian organisms: a regulator of glucose metabolism and other key signaling pathways. Insulin is also a multifunctional hormone whose absence can cause many diseases. Recombinant insulin is widely used in the treatment of diabetes. Understanding insulin, biosimilars, and biobetters from a holistic perspective will help pharmacologically user-friendly molecules design and develop personalized medicine-oriented therapeutic strategies for diabetes. Additionally, it helps to understand the underlying mechanism of other insulin-dependent metabolic disorders. The purpose of this atlas is to review insulin from a biotechnologi-cal, basic science, and clinical perspective, explain nearly all insulin-related disorders and their underlying molecular mechanisms, explore exogenous/recombinant production strategies of patented and research-level insulin/analogs, and highlight their mechanism of action from a structural per-spective. Combined with computational analysis, comparisons of insulin and analogs also provide novel information about the structural dynamics of insulin.Publication Metadata only A chemically inducible organelle rerouting assay to probe primary cilium assembly, maintenance, and disassembly in cultured cells(Humana Press Inc., 2024) Department of Molecular Biology and Genetics; İşsezer, Fatma Başak Turan; Ercan, Muhammed Erdem; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of SciencesThe primary cilium is a conserved, microtubule-based organelle that protrudes from the surface of most vertebrate cells as well as sensory cells of many organisms. It transduces extracellular chemical and mechanical cues to regulate diverse cellular processes during development and physiology. Loss-of-function studies via RNA interference and CRISPR/Cas9-mediated gene knockouts have been the main tool for elucidating the functions of proteins, protein complexes, and organelles implicated in cilium biology. However, these methods are limited in studying acute spatiotemporal functions of proteins as well as the connection between their cellular positioning and functions. A powerful approach based on inducible recruitment of plus or minus end-directed molecular motors to the protein of interest enables fast and precise control of protein activity in time and in space. In this chapter, we present a chemically inducible heterodimerization method for functional perturbation of centriolar satellites, an emerging membrane-less organelle involved in cilium biogenesis and function. The method we present is based on rerouting of centriolar satellites to the cell center or the periphery in mammalian epithelial cells. We also describe how this method can be applied to study the temporal functions of centriolar satellites during primary cilium assembly, maintenance, and disassembly.Publication Metadata only A CLOCK-binding small molecule disrupts the interaction between CLOCK and BMAL1 and enhances circadian rhythm amplitude(Elsevier, 2020) Akyel, Yasemin Kübra; Yılmaz, Fatma; Öztürk, Nuri; Öztürk, Narin; Okyar, Alper; N/A; N/A; Department of Chemical and Biological Engineering; N/A; Department of Molecular Biology and Genetics; Department of Industrial Engineering; Department of Chemical and Biological Engineering; Doruk, Yağmur Umay; Yarparvar, Darya; Gül, Şeref; Taşkın, Ali Cihan; Barış, İbrahim; Türkay, Metin; Kavaklı, İbrahim Halil; Master Student; PhD Student; Researcher; Other; Teaching Faculty; Faculty Member; Faculty Member; Department of Molecular Biology and Genetics; Department of Industrial Engineering; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; College of Sciences; College of Engineering; College of Engineering; N/A; N/A; N/A; 291296; 111629; 24956; 40319Proper function of many physiological processes requires a robust circadian clock. Disruptions of the circadian clock can result in metabolic diseases, mood disorders, and accelerated aging. Therefore, identifying small molecules that specifically modulate regulatory core clock proteins may potentially enable better management of these disorders. In this study, we applied a structure-based molecular-docking approach to find small molecules that specifically bind to the core circadian regulator, the transcription factor circadian locomotor output cycles kaput (CLOCK). We identified 100 candidate molecules by virtual screening of ?2 million small molecules for those predicted to bind closely to the interface in CLOCK that interacts with its transcriptional co-regulator, Brain and muscle Arnt-like protein-1 (BMAL1). Using a mammalian two-hybrid system, real-time monitoring of circadian rhythm in U2OS cells, and various biochemical assays, we tested these compounds experimentally and found one, named CLK8, that specifically bound to and interfered with CLOCK activity. We show that CLK8 disrupts the interaction between CLOCK and BMAL1 and interferes with nuclear translocation of CLOCK both in vivo and in vitro. Results from further experiments indicated that CLK8 enhances the amplitude of the cellular circadian rhythm by stabilizing the negative arm of the transcription/translation feedback loop without affecting period length. Our results reveal CLK8 as a tool for further studies of CLOCK's role in circadian rhythm amplitude regulation and as a potential candidate for therapeutic development to manage disorders associated with dampened circadian rhythms.Publication Open Access A disconnect between upslope shifts and climate change in an Afrotropical bird community(Wiley, 2020) Neate-Clegg, Montague H. C.; O'Brien, Timothy G.; Mulindahabi, Felix; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589Climate change threatens to push species to higher elevations and eventual extinction. Birds, in particular, are shown to be shifting upslope in the Neotropics and Southeast Asia. Yet previous studies have lacked the temporal resolution to investigate distributional dynamics over time in relation to climatic fluctuations, especially in the understudied Afrotropics. Here, we used 15 years of point-count data from across an elevational gradient (1,767-2,940 m) in Rwanda, to assess elevational shift rates and dynamics in a community of Afrotropical birds. In general, species shifted their elevations upslope by 1.9 m/year, especially at their lower elevational limits which shifted by 4.4 m/year. Importantly, these shifts occurred despite the fact that local temperature and precipitation showed little trend over the study period. Moreover, the interannual distributions of few species were associated with temperature, suggesting that temperature played little direct role in determining elevational distributions of birds. Instead, upslope shifts may be more related to incremental shifts in habitat and resources which lag behind decades of increased temperature in the region. Precipitation appeared to have more of an effect than temperature in determining interannual elevational changes, allowing species to expand their ranges in years of higher rainfall. Our results highlight the need to understand the mechanisms driving upslope shifts as they occur throughout the tropics. It will be critical for montane regions of the tropics to preserve contiguous blocks of forest across elevational gradients to allow wildlife to shift unimpeded.Publication Open Access A new genus and species of spionid polychaete (Annelida, Spionidae) from a deep-water cold seep site in the Eastern Mediterranean Sea off Turkey(Magnolia Press, 2020) Blake, James A.; Department of Molecular Biology and Genetics; Balcı, Patricia A. Ramey; Researcher; Department of Molecular Biology and Genetics; College of Sciences; 261777A new spionid polychaete was discovered in deep-sea sediments in the eastern Mediterranean Sea during an expedition by the Ocean Exploration Trust. Specimens were collected by the E/V Nautilus in August 2012 off Turkey, at a depth of 2216 m on the Anaximander Seamount at the Amsterdam mud volcano site. Cores were taken from sediments covered with microbial mats. The new species belongs to the Pygospiopsis-Atherospio Group, which has unusual neuropodial hooks, modified neurosetae in some anterior setigers, and branchiae in middle body segments that are broad, flattened, and fused to the dorsal lamellae. The new species is assigned to a new genus and species, Aciculaspio anaximanderi n. gen., n. sp., and is unusual in having a reduced setiger 1 lacking notosetae; well-developed pre- and postsetal lamellae that encompass the neurosetae and notosetae; notopodial lamellae free from the branchiae in anterior setigers that become fused and flattened in middle and posterior segments; unidentate hooded hooks in both noto- and neuropodia; neuropodial spines in setigers 4-10; and a pygidium with three anal cirri. Aciculaspio anaximanderi n. gen., n. sp. is the first species in the Atherospio-Pygospiopsis Group collected from a deep-water cold seep habitat.Publication Open Access A new series of indeno[1,2-c]pyrazoles as EGFR TK inhibitors for NSCLC therapy(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Özdemir, A.; Sever, B.; Tateishi, H.; Otsuka, M.; Fujita, M.; Altıntop, M.D.; Department of Molecular Biology and Genetics; Çiftçi, Halil İbrahim; Department of Molecular Biology and Genetics; College of SciencesNon-small cell lung cancer (NSCLC) is the leading cause of cancer-related death throughout the world. Due to the shortcomings of traditional chemotherapy, targeted therapies have come into prominence for the management of NSCLC. In particular, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy has emerged as a first-line therapy for NSCLC patients with EGFR-activating mutations. In this context, new indenopyrazoles, which were prepared by an efficient microwave-assisted method, were subjected to in silico and in vitro assays to evaluate their potency as EGFR TK-targeted anti-NSCLC agents. Compound 4 was the most promising antitumor agent towards A549 human lung adenocarcinoma cells, with an IC50 value of 6.13 µM compared to erlotinib (IC50 = 19.67 µM). Based on its low cytotoxicity to peripheral blood mononuclear cells (PBMCs), it can be concluded that compound 4 exerts selective antitumor action. This compound also inhibited EGFR TK with an IC50 value of 17.58 µM compared to erlotinib (IC50 = 0.04 µM) and induced apoptosis (56.30%). Taking into account in silico and in vitro data, compound 4 stands out as a potential EGFR TKI for the treatment of NSCLC.Publication Open Access A proximity mapping journey into the biology of the mammalian centrosome/cilium complex(Multidisciplinary Digital Publishing Institute (MDPI), 2020) Department of Molecular Biology and Genetics; Arslanhan, Melis Dilara; Gülensoy, Dila; Karalar, Elif Nur Fırat; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; 206349The mammalian centrosome/cilium complex is composed of the centrosome, the primary cilium and the centriolar satellites, which together regulate cell polarity, signaling, proliferation and motility in cells and thereby development and homeostasis in organisms. Accordingly, deregulation of its structure and functions is implicated in various human diseases including cancer, developmental disorders and neurodegenerative diseases. To better understand these disease connections, the molecular underpinnings of the assembly, maintenance and dynamic adaptations of the centrosome/cilium complex need to be uncovered with exquisite detail. Application of proximity-based labeling methods to the centrosome/cilium complex generated spatial and temporal interaction maps for its components and provided key insights into these questions. In this review, we first describe the structure and cell cycle-linked regulation of the centrosome/cilium complex. Next, we explain the inherent biochemical and temporal limitations in probing the structure and function of the centrosome/cilium complex and describe how proximity-based labeling approaches have addressed them. Finally, we explore current insights into the knowledge we gained from the proximity mapping studies as it pertains to centrosome and cilium biogenesis and systematic characterization of the centrosome, cilium and centriolar satellite interactomes.Publication Metadata only A structural basis for restricted codon recognition mediated by 2-thiocytidine in tRNA containing a wobble position inosine(Elsevier, 2020) Vangaveti, Sweta; Cantara, William A.; Spears, Jessica L.; Murphy, Frank V.; Ranganathan, Sri V.; Sarachan, Kathryn L.; Agris, Paul F.; Department of Molecular Biology and Genetics; Demirci, Hasan; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 307350Three of six arginine codons (CGU, CGC, and CGA) are decoded by two Escherichia coli tRNA(Arg) isoacceptors. The anticodon stem and loop (ASL) domains of tRNA(Arg1) and tRNA(Arg2) both contain inosine and 2-methyladenosine modifications at positions 34 (I-34) and 37 (m(2)A(37)). tRNA(Arg1) is also modified from cytidine to 2-thiocytidine at position 32 (s(2)C(32)). The s(2)C(32) modification is known to negate wobble codon recognition of the rare CGA codon by an unknown mechanism, while still allowing decoding of CGU and CGC. Substitution of s(2)C(32) for C-32 in the Saccharomyces cerevisiae tRNA(IAU)(lle) anticodon stem and loop domain (ASL) negates wobble decoding of its synonymous A-ending codon, suggesting that this function of s(2)C at position 32 is a generalizable property. X-ray crystal structures of variously modified ASL(ICG)(Arg1) and ASL(ICG)(Arg2) constructs bound to cognate and wobble codons on the ribosome revealed the disruption of a C-32-A(38) cross-loop interaction but failed to fully explain the means by which s(2)C(32) restricts I-34 wobbling. Computational studies revealed that the adoption of a spatially broad inosine-adenosine base pair at the wobble position of the codon cannot be maintained simultaneously with the canonical ASL U-turn motif. C-32-A(38) cross-loop interactions are required for stability of the anticodon/codon interaction in the ribosomal A-site.Publication Metadata only A tour de force of primary cilium biogenesis(Nature Portfolio, 2021) N/A; Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 206349N/A