Research Outputs
Permanent URI for this communityhttps://hdl.handle.net/20.500.14288/2
Browse
42 results
Search Results
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 Alteration of cell motility dynamics through collagen fiber density in photopolymerized polyethylene glycol hydrogels(Elsevier, 2020) Bayraktar, Halil; N/A; Akalın, Özge Begüm; Master Student; Graduate School of Sciences and Engineering; N/APolyethylene glycol (PEG) hydrogels that have natural fibers mimicking extracellular matrix can be used as a model to understand the role of substrate properties on cell growth and migration. Due to the dependence of cell movement to adhesion, characterization of motility is needed to prepare biocompatible substrates. We demonstrated a method to encapsulate collagen into PEG hydrogel crosslinked via photopolymerization and studied the effect of fiber density on motility dynamics. Porous hydrogel immersed into collagen solution was coated with fibers after neutralizing solution. We provided a detailed study of cell instantaneous/average speed, total displacement, persistence and angular displacement. We found that cells demonstrated a biphasic motility where a maximum speed of 17.4 mu m/h with a total distance of 215 mu m and persistence of 0.43 were obtained at 12 mg/ml collagen. High occurrence of low angular displacement observed at intermediate fiber density suggests that cells tend to move forward along hydrogels. Increased anisotropy at low density was an indication of forward and backward movement. Finally, matrix deformation was determined in the absence of fluorescent beads by tracking fiber displacement at subpixel resolution. Our findings establish a method for preparation of collagen coated hydrogels and provide an insight into cell motility dynamics.Publication Metadata only Attenuation of Type IV pili activity by natural products(Taylor & Francis Inc, 2024) Yalkut, Kerem; Hassine, Soumaya Ben Ali; Kula, Ceyda; Ozcan, Aslihan; Avci, Fatma Gizem; Akbulut, Berna Sariyar; Ozbek, Pemra; Department of Chemical and Biological Engineering; Başaran, Esra; Keskin, Özlem; Department of Chemical and Biological Engineering; Graduate School of Sciences and Engineering; College of EngineeringThe virulence factor Type IV pili (T4P) are surface appendages used by the opportunistic pathogen Pseudomonas aeruginosa for twitching motility and adhesion in the environment and during infection. Additionally, the use of these appendages by P. aeruginosa for biofilm formation increases its virulence and drug resistance. Therefore, attenuation of the activity of T4P would be desirable to control P. aeruginosa infections. Here, a computational approach has been pursued to screen natural products that can be used for this purpose. PilB, the elongation ATPase of the T4P machinery in P. aeruginosa, has been selected as the target subunit and virtual screening of FDA-approved drugs has been conducted. Screening identified two natural compounds, ergoloid and irinotecan, as potential candidates for inhibiting this T4P-associated ATPase in P. aeruginosa. These candidate compounds underwent further rigorous evaluation through molecular dynamics (MD) simulations and then through in vitro twitching motility and biofilm inhibition assays. Notably, ergoloid emerged as a particularly promising candidate for weakening the T4P activity by inhibiting the elongation ATPases associated with T4P. This repurposing study paves the way for the timely discovery of antivirulence drugs as an alternative to classical antibiotic treatments to help combat infections caused by P. aeruginosa and related pathogens.Publication Metadata only Cancer-associated fibroblasts: Protagonists of the tumor microenvironment in gastric cancer(Frontiers Media Sa, 2024) Özmen, Ece; Demir, Tevriz Dilan; Özcan, Gülnihal; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of MedicineEnhanced knowledge of the interaction of cancer cells with their environment elucidated the critical role of tumor microenvironment in tumor progression and chemoresistance. Cancer-associated fibroblasts act as the protagonists of the tumor microenvironment, fostering the metastasis, stemness, and chemoresistance of cancer cells and attenuating the anti-cancer immune responses. Gastric cancer is one of the most aggressive cancers in the clinic, refractory to anti-cancer therapies. Growing evidence indicates that cancer-associated fibroblasts are the most prominent risk factors for a poor tumor immune microenvironment and dismal prognosis in gastric cancer. Therefore, targeting cancer-associated fibroblasts may be central to surpassing resistance to conventional chemotherapeutics, molecular-targeted agents, and immunotherapies, improving survival in gastric cancer. However, the heterogeneity in cancer-associated fibroblasts may complicate the development of cancer-associated fibroblast targeting approaches. Although single-cell sequencing studies started dissecting the heterogeneity of cancer-associated fibroblasts, the research community should still answer these questions: "What makes a cancer-associated fibroblast protumorigenic?";"How do the intracellular signaling and the secretome of different cancer-associated fibroblast subpopulations differ from each other?";and "Which cancer-associated fibroblast subtypes predominate specific cancer types?". Unveiling these questions can pave the way for discovering efficient cancer-associated fibroblast targeting strategies. Here, we review current knowledge and perspectives on these questions, focusing on how CAFs induce aggressiveness and therapy resistance in gastric cancer. We also review potential therapeutic approaches to prevent the development and activation of cancer-associated fibroblasts via inhibition of CAF inducers and CAF markers in cancer.Publication Metadata only Chitosan in cancer therapy: a dual role as a therapeutic agent and drug delivery system(Walter de Gruyter Gmbh, 2024) Atmaca, Harika; Ilhan, Suleyman; N/A; Oğuz, Ferdi; Graduate School of Health SciencesAlthough chemotherapy is still the most preferred treatment for cancer, most chemotherapeutic agents target both cancer cells and healthy cells and cause serious side effects due to high toxicity. Improved drug delivery systems (DDSs), which enhance the efficacy of current chemotherapeutic drugs while reducing their toxicity, offer potential solutions to these challenges. Chitosan (CS) and its derivatives are biopolymers with biodegradable, biocompatible, and low-toxicity properties, and their structure allows for convenient chemical and mechanical modifications. In its role as a therapeutic agent, CS can impede the proliferation of tumor cells through the inhibition of angiogenesis and metastasis, as well as by triggering apoptosis. CS and its derivatives are also frequently preferred as DDSs due to their properties such as high drug-carrying capacity, polycationic structure, long-term circulation, and direct targeting of cancer cells. Various therapeutic agents linked to CS and its derivatives demonstrate potent anticancer effects with advantages such as reduced side effects compared to the original drugs, owing to factors like targeted distribution within cancer tissues and sustained release. This review emphasizes the utilization of CS and its derivatives, both as therapeutic agents and as carriers for established chemotherapeutic drugs.Publication Metadata only CilioGenics: an integrated method and database for predicting novel ciliary genes(Oxford Univ Press Inc, 2024) Pir, Mustafa S.; Yenisert, Ferhan; Demirci, Hasan C.; Korkmaz, Mustafa E.; Karaman, Asli; Tsiropoulou, Sofia; Blacque, Oliver E.; Oner, Sukru S.; Doluca, Osman; Cevik, Sebiha; Kaplan, Oktay, I; Department of Molecular Biology and Genetics; Begar, Efe; Karalar, Elif Nur Fırat; Department of Molecular Biology and Genetics; ; Graduate School of Sciences and Engineering; College of Sciences;Uncovering the full list of human ciliary genes holds enormous promise for the diagnosis of cilia-related human diseases, collectively known as ciliopathies. Currently, genetic diagnoses of many ciliopathies remain incomplete (). While various independent approaches theoretically have the potential to reveal the entire list of ciliary genes, approximately 30% of the genes on the ciliary gene list still stand as ciliary candidates (,). These methods, however, have mainly relied on a single strategy to uncover ciliary candidate genes, making the categorization challenging due to variations in quality and distinct capabilities demonstrated by different methodologies. Here, we develop a method called CilioGenics that combines several methodologies (single-cell RNA sequencing, protein-protein interactions (PPIs), comparative genomics, transcription factor (TF) network analysis, and text mining) to predict the ciliary capacity of each human gene. Our combined approach provides a CilioGenics score for every human gene that represents the probability that it will become a ciliary gene. Compared to methods that rely on a single method, CilioGenics performs better in its capacity to predict ciliary genes. Our top 500 gene list includes 258 new ciliary candidates, with 31 validated experimentally by us and others. Users may explore the whole list of human genes and CilioGenics scores on the CilioGenics database (https://ciliogenics.com/).Publication Metadata only Comparative molecular dynamics simulations of amphotericin B-cholesterol/ergosterol membrane channels(Elsevier, 2002) Baginski, Maciej; Borowski, Edward; Department of Physics; Reşat, Haluk; Faculty Member; Department of Physics; College of Sciences; N/AAmphotericin B (AmB) is a very effective anti-fungal polyene macrolide antibiotic whose usage is limited by its toxicity. Lack of a complete understanding of AmB's molecular mechanism has impeded attempts to design less toxic AmB derivatives. The antibiotic is known to interact with sterols present in the cell membrane to form ion channels that disrupt membrane function. The slightly higher affinity of AmB toward ergosterol (dominant sterol in fungal cells) than cholesterol (mammalian sterol) is regarded as the most essential factor on which antifungal chemotherapy is based. To study these differences at the molecular level, two realistic model membrane channels containing molecules of AmB, sterol (cholesterol or ergosterol), phospholipid, and water were studied by molecular dynamics (MID) simulations. Comparative analysis of the simulation data revealed that the sterol type has noticeable effect on the properties of AmB membrane channels. In addition to having a larger size, the AmB channel in the ergosterol-containing membrane has a more pronounced pattern of intermolecular hydrogen bonds. The interaction between the antibiotic and ergosterol is more specific than between the antibiotic and cholesterol. These observed differences suggest that the channel in the ergosterol-containing membrane is more stable and, due to its larger size, would have a higher ion conductance. These observations are in agreement with experiments. (C) 2002 Elsevier Science B.V. All rights reserved.Publication Metadata only Conservation of migratory species(Cell Press, 2018) Horns, Joshua J.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589N/APublication Metadata only Cornerstones of biochemistry in stamps(Walter De Gruyter Gmbh, 2016) N/A; Ulusu, Nuriye Nuray; Faculty Member; School of Medicine; 6807N/APublication Metadata only COVID-19 may enhance risk of thrombosis and hemolysis in the G6PD deficient patients(Taylor & Francis Inc, 2021) Dağlıoğlu, Gülçin; Candevir, Aslıhan; Kurtaran, Behice; Bozdoğan, Sevcan Tan; İnal, Tamer Cevat; N/A; Aydemir, Duygu; Ulusu, Nuriye Nuray; PhD Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; School of Medicine; N/A; 6807COVID-19 has become a major public health problem since December, 2019 and no highly effective drug has been found until now. Numbers of infected people and deaths by COVID-19 are increasing every day worldwide, therefore self-isolation and protection are highly recommended to prevent the spread of the virus and especially to protect major risk groups such as the elderly population and people with comorbidities including diabetes, hypertension, cancer, cardiovascular diseases and metabolic syndrome. on the other hand, young people without any secondary disease have died by COVID-19 as well. In this study we compared two male patients infected by COVID-19 at the same age and one of them was diagnosed with G6PD deficiency. Both COVID-19and G6PD deficiency enhance the risk of hemolysis and thrombosis. Serum biochemistry, hemogram and immunological parameters showed that risk of hemolysis and thrombosis may increase in the G6PD deficient patient infected by COVID-19.