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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 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 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 Open Access Acute inhibition of centriolar satellite function and positioning reveals their functions at the primary cilium(Public Library of Science, 2020) Department of Molecular Biology and Genetics; 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; N/A; 206349Centriolar satellites are dynamic, membraneless granules composed of over 200 proteins. They store, modify, and traffic centrosome and primary cilium proteins, and help to regulate both the biogenesis and some functions of centrosomes and cilium. In most cell types, satellites cluster around the perinuclear centrosome, but their integrity and cellular distribution are dynamically remodeled in response to different stimuli, such as cell cycle cues. Dissecting the specific and temporal functions and mechanisms of satellites and how these are influenced by their cellular positioning and dynamics has been challenging using genetic approaches, particularly in ciliated and proliferating cells. To address this, we developed a chemical-based trafficking assay to rapidly and efficiently redistribute satellites to either the cell periphery or center, and fuse them into stable clusters in a temporally controlled way. Induced satellite clustering at either the periphery or center resulted in antagonistic changes in the pericentrosomal levels of a subset of proteins, revealing a direct and selective role for their positioning in protein targeting and sequestration. Systematic analysis of the interactome of peripheral satellite clusters revealed enrichment of proteins implicated in cilium biogenesis and mitosis. Importantly, induction of peripheral satellite targeting in ciliated cells revealed a function for satellites not just for efficient cilium assembly but also in the maintenance of steady-state cilia and in cilia disassembly by regulating the structural integrity of the ciliary axoneme. Finally, perturbing satellite distribution and dynamics inhibited their mitotic dissolution, and mitotic progression was perturbed only in cells with centrosomal satellite clustering. Collectively, our results for the first time showed a direct link between satellite functions and their pericentrosomal clustering, suggested new mechanisms underlying satellite functions during cilium assembly, and provided a new tool for probing temporal satellite functions in different contextsPublication Open Access An advanced workflow for single-particle imaging with the limited data at an X-ray free-electron laser(International Union of Crystallography, 2020) Assalauova, Dameli; Kim, Young Yong; Bobkov, Sergey; Khubbutdinov, Ruslan; Rose, Max; Alvarez, Roberto; Andreasson, Jakob; Balaur, Eugeniu; Contreras, Alice; Gelisio, Luca; Hajdu, Janos; Hunter, Mark S.; Kurta, Ruslan P.; Li, Haoyuan; McFadden, Matthew; Nazari, Reza; Schwander, Peter; Teslyuk, Anton; Walter, Peter; Xavier, P. Lourdu; Yoon, Chun Hong; Zaare, Sahba; Ilyin, Viacheslav A.; Kirian, Richard A.; Hogue, Brenda G.; Aquila, Andrew; Vartanyants, Ivan A.; Department of Molecular Biology and Genetics; Demirci, Hasan; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 307350An improved analysis for single-particle imaging (SPI) experiments, using the limited data, is presented here. Results are based on a study of bacteriophage PR772 performed at the Atomic, Molecular and Optical Science instrument at the Linac Coherent Light Source as part of the SPI initiative. Existing methods were modified to cope with the shortcomings of the experimental data: inaccessibility of information from half of the detector and a small fraction of single hits. The general SPI analysis workflow was upgraded with the expectation-maximization based classification of diffraction patterns and mode decomposition on the final virus-structure determination step. The presented processing pipeline allowed us to determine the 3D structure of bacteriophage PR772 without symmetry constraints with a spatial resolution of 6.9 nm. The obtained resolution was limited by the scattering intensity during the experiment and the relatively small number of single hits.Publication Open Access Anti-inflammatory modulation of microglia via CD163-targeted glucocorticoids protects dopaminergic neurons in the 6-OHDA Parkinson's disease model(Society for Neuroscience, 2016) Tentillier, Noemie; Etzerodt, Anders; Olesen, Mads N.; Jacobsen, Jan; Bender, Dirk; Moestrup, Soren K.; Romero-Ramos, Marina; Department of Molecular Biology and Genetics; Rızalar, F. Sıla; Department of Molecular Biology and Genetics; Graduate School of Sciences and EngineeringIncreasing evidence supports a decisive role for inflammation in the neurodegenerative process of Parkinson's disease (PD). The immune response in PD seems to involve, not only microglia, but also other immune cells infiltrated into the brain. Indeed, we observed here the infiltration of macrophages, specifically CD163+ macrophages, into the area of neurodegeneration in the 6-hydroxydopamine (6-OHDA) PD model. Therefore, we investigated the therapeutic potential of the infiltrated CD163+ macrophages to modulate local microglia in the brain to achieve neuroprotection. To do so, we designed liposomes targeted for the CD163 receptor to deliver dexamethasone (Dexa) into the CD163+ macrophages in the 6-OHDA PD model. Our data show that a fraction of the CD163-targeted liposomes were carried into the brain after peripheral intravenous injection. The 6-OHDA-lesioned rats that received repeated intravenous CD163-targeted liposomes with Dexa for 3 weeks exhibited better motor performance than the control groups and had minimal glucocorticoid-driven side effects. Furthermore, these animals showed better survival of dopaminergic neurons in substantia nigra and an increased number of microglia expressing major histocompatibility complex II. Therefore, rats receiving CD163-targeted liposomes with Dexa were partially protected against 6-OHDA-induced dopaminergic neurodegeneration, which correlated with a distinctive microglia response. Altogether, our data support the use of macrophages for the modulation of brain neurodegeneration and specifically highlight the potential of CD163-targeted liposomes as a therapeutic tool in PD.Publication Open Access Association between gene polymorphisms in TIM1, TSLP, IL18R1 and childhood asthma in Turkish population(e-Century Publishing Corporation, 2014) Mete, Fatih; Özkaya, Emin; Aras, Şükrü; Köksal, Vedat; Etlik, Özdal; Department of Molecular Biology and Genetics; Barış, İbrahim; Teaching Faculty; Department of Molecular Biology and Genetics; College of Sciences; 111629Many immunologic and inflammatory mechanisms play a role in asthma etiology. The aim of this study was to investigate the susceptibility of asthma patients in the Turkish population with demonstrating genes for polymorphisms in TIM1, TSLP and IL18R1. All of the genomic DNA samples were isolated from blood samples according to a standard salting-out protocol. DNA samples were stored at -20 degrees C until the genotype analysis was performed. rs3806933 (TSLP -847 C > T) and TIM1 -416G > C were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The rs3806933 (TSLP -847 C > T) was genotyped by PCR using our new primers and HphI restriction enzyme digestion. rs2287033 (IL18R1 c. 1270+150 A > G), rs3213733 (IL18R1 c. 626-196 G > T), and rs3771166 (IL18R1-c. 302+1694 C > T) were genotyped using SYBR green dye based real time PCR assay. Results: The allele frequencies of 5 SNPs in TSLP, TIM-1, and IL18R1 genes were determined in 139 asthmatic patients and 126 healthy controls of in Turkish population. The investigated SNPs are as follows; rs3806933 (TSLP -847 C > T), TIM1 -416G > C, rs2287033 (IL18R1 c. 1270+150 A > G), rs3213733 (IL18R1 c. 626-196 G > T), and rs3771166 (IL18R1-c. 302+1694 C > T). Results suggest that IL18R1 c. 626-196 G > T (rs3213733) and TIM1 -416G > C are significantly associated with asthma in patients in Turkish population. Patients with AA genotypes of rs2287033 (IL18R1 c. 1270+150 A > G), have significantly less total serum IgE levels when compared with patients having GG or GA genotypes (p < 0.012; 381.77 +/- 239.46 vs 557.52 +/- 549.96, respectively). Conclusion: This study showed that IL18R1 c. 626 -196 G > T (rs3213733) and TIM1 -416G > C are significantly associated with asthma patients in Turkish population.Publication Metadata only Atmospheric pressure plasma jet treatment of human hair fibers(2015) N/A; N/A; Department of Molecular Biology and Genetics; Department of Chemistry; Birer, Özgür; Acar, Erhan; Keleş, Merve; Öngel, Cansu; Researcher; Master Student; Undergraduate Student; Undergraduate Student; Department of Molecular Biology and Genetics; Department of Chemistry; Koç University Surface Science and Technology Center (KUYTAM) / Koç Üniversitesi Yüzey Teknolojileri Araştırmaları Merkezi (KUYTAM); N/A; Graduate School of Sciences and Engineering; College of Science; College of Science; N/A; N/A; N/A; N/AHuman hair fibers in virgin and dyed forms were treated with atmospheric pressure helium, helium/oxygen, argon, and argon/oxygen plasma jets at 20 W of power. The effects of 10-min plasma treatment on surface morphology and chemistry were studied by scanning electron microscopy and X-ray photoelectron spectroscopy, respectively. The plasma treatment was quite effective for removing the organic residues from the surface and creating oxidized functional groups. Helium plasma had a mild cleaning effect on the surfaces while argon/oxygen plasma had the strongest corrosive effect. Mild hydrogen peroxide treatment for the same duration had neither the cleaning nor the oxidizing power of the plasma jets. These types of plasma jets have the potential to replace peroxide treatment. The corrosive jets can be used to restore dyed hair fibers. In addition, the jets can be used to clean the surfaces of hair fibers to prepare samples for analytical investigations where the organic residues may induce problems. © 2015, Springer International Publishing AG.Publication Open Access Band alignment engineers faradaic and capacitive photostimulation of neurons without surface modification(American Physical Society (APS), 2019) Department of Electrical and Electronics Engineering; N/A; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Srivastava, Shashi Bhushan; Melikov, Rustamzhon; Aria, Mohammad Mohammadi; Dikbaş, Uğur Meriç; Kavaklı, İbrahim Halil; Nizamoğlu, Sedat; Researcher; PhD Student; Master Student; Faculty Member; Faculty Member; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; College of Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; N/A; N/A; N/A; 40319; 130295Photovoltaic substrates have attracted significant attention for neural photostimulation. The control of the Faradaic and capacitive (non-Faradaic) charge transfer mechanisms by these substrates are critical for safe and effective neural photostimulation. We demonstrate that the intermediate layer can directly control the strength of the capacitive and Faradaic processes under physiological conditions. To resolve the Faradaic and capacitive stimulations, we enhance photogenerated charge density levels by incorporating PbS quantum dots into a poly(3-hexylthiophene-2,5-diyl):([6,6]-Phenyl-C61-butyric acid methyl ester (P3HT:PCBM) blend. This enhancement stems from the simultaneous increase of absorption, well matched band alignment of PbS quantum dots with P3HT:PCBM, and smaller intermixed phase-separated domains with better homogeneity and roughness of the blend. These improvements lead to the photostimulation of neurons at a low light intensity level of 1 mW cm(-2), which is within the retinal irradiance level. These findings open up an alternative approach toward superior neural prosthesis.