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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6

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Open Access
A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells
(Nature Publishing Group (NPG), 2018) Seferoğlu, Ayşe Bengisu; Department of Molecular Biology and Genetics; Dunn, Cory David; Keskin, Abdurrahman; Akdoğan, Emel; Lutfullahoglu-Bal, Guleycan; Department of Molecular Biology and Genetics; College of Sciences
Prokaryotes can provide new genetic information to eukaryotes by horizontal gene transfer (HGT), and such transfers are likely to have been particularly consequential in the era of eukaryogenesis. Since eukaryotes are highly compartmentalized, it is worthwhile to consider the mechanisms by which newly transferred proteins might reach diverse organellar destinations. Toward this goal, we have focused our attention upon the behavior of bacteria-derived tail anchors (TAs) expressed in the eukaryote Saccharomyces cerevisiae. In this study, we report that a predicted membrane-associated domain of the Escherichia coli YgiM protein is specifically trafficked to peroxisomes in budding yeast, can be found at a pre-peroxisomal compartment (PPC) upon disruption of peroxisomal biogenesis, and can functionally replace an endogenous, peroxisome-directed TA. Furthermore, the YgiM(TA) can localize to peroxisomes in mammalian cells. Since the YgiM(TA) plays no endogenous role in peroxisomal function or assembly, this domain is likely to serve as an excellent tool allowing further illumination of the mechanisms by which TAs can travel to peroxisomes. Moreover, our findings emphasize the ease with which bacteria-derived sequences might target to organelles in eukaryotic cells following HGT, and we discuss the importance of flexible recognition of organelle targeting information during and after eukaryogenesis.
Open Access
A cartridge based sensor array platform for multiple coagulation measurements from plasma
(Royal Society of Chemistry (RSC), 2015) Bulut, Serpil; Yaralioglu, G. G.; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; Çakmak, Onur; Ermek, Erhan; Kılınç, Necmettin; Barış, İbrahim; Kavaklı, İbrahim Halil; Ürey, Hakan; PhD Student; Other; Researcher; Teaching Faculty; Faculty Member; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Department of Chemical and Biological Engineering; College of Engineering; Graduate School of Sciences and Engineering; College of Sciences; N/A; 109991; N/A; 111629; 40319; 8579
This paper proposes a MEMS-based sensor array enabling multiple clot-time tests for plasma in one disposable microfluidic cartridge. The versatile LoC (Lab-on-Chip) platform technology is demonstrated here for real-time coagulation tests (activated Partial Thromboplastin Time (aPTT) and Prothrombin Time (PT)). The system has a reader unit and a disposable cartridge. The reader has no electrical connections to the cartridge. This enables simple and low-cost cartridge designs and avoids reliability problems associated with electrical connections. The cartridge consists of microfluidic channels and MEMS microcantilevers placed in each channel. The microcantilevers are made of electroplated nickel. They are actuated remotely using an external electro-coil and the read-out is also conducted remotely using a laser. The phase difference between the cantilever oscillation and the coil drive is monitored in real time. During coagulation, the viscosity of the blood plasma increases resulting in a change in the phase read-out. The proposed assay was tested on human and control plasma samples for PT and aPTT measurements. PT and aPTT measurements from control plasma samples are comparable with the manufacturer's datasheet and the commercial reference device. The measurement system has an overall 7.28% and 6.33% CV for PT and aPTT, respectively. For further implementation, the microfluidic channels of the cartridge were functionalized for PT and aPTT tests by drying specific reagents in each channel. Since simultaneous PT and aPTT measurements are needed in order to properly evaluate the coagulation system, one of the most prominent features of the proposed assay is enabling parallel measurement of different coagulation parameters. Additionally, the design of the cartridge and the read-out system as well as the obtained reproducible results with 10 mu l of the plasma samples suggest an opportunity for a possible point-of-care application.
Open Access
A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells
(National Academy of Sciences, 2010) Sulis, M.L.; Ferrando, A.A.; Greenwald, I.; Department of Molecular Biology and Genetics; Dunn, Cory David; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences
The cytosolic domain of Notch is a membrane-tethered transcription factor. Ligand binding ultimately leads to γ-secretase cleavage within the transmembrane domain, allowing the intracellular domain to translocate to the nucleus and activate target gene transcription. Constitutive Notch signaling has been associated with human cancers such as T cell acute lymphoblastic leukemia (T-ALL). As tetraspanins have been implicated in many different signaling processes, we assessed their potential contribution to Notch signaling. We used a genetic assay in Caenorhabditis elegans to identify TSP-12 as a positive factor for Notch activity in several cellular contexts. Then, using a cell culture system, we showed that two human TSP-12 orthologs, TSPAN33 and TSPAN5, promote Notch activity and are likely to act at the γ-secretase cleavage step. We also acquired evidence for functional redundancy among tetraspanins in both C. elegans and human cells. Selective inhibition of tetraspanins may constitute an anti-NOTCH therapeutic approach to reduce γ-secretase activity.
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; 327589
Climate 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.
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; 261777
A 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.
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 Sciences
Non-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.
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; 206349
The 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.
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; 206349
Centriolar 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 contexts
Open Access
AF10 (MLLT10) prevents somatic cell reprogramming through regulation of DOT1L-mediated H3K79 methylation
(BioMed Central, 2021) Philpott, Martin; Oppermann, Udo; Department of Molecular Biology and Genetics; Önder, Tamer Tevfik; Uğurlu Çimen, Deniz; Sevinç, Kenan; Küçük, Nazlı Ezgi Özkan; Özçimen, Burcu; Demirtaş, Deniz; Enüstün, Eray; Faculty Member; Faculty Member; PhD Student; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; College of Sciences; Graduate School of Sciences and Engineering; Graduate School of Health Sciences; 42946; 105301; N/A; N/A; N/A; N/A; N/A; N/A; N/A; N/A
Background: the histone H3 lysine 79 (H3K79) methyltransferase DOT1L is a key chromatin-based barrier to somatic cell reprogramming. However, the mechanisms by which DOT1L safeguards cell identity and somatic-specific transcriptional programs remain unknown. Results: we employed a proteomic approach using proximity-based labeling to identify DOT1L-interacting proteins and investigated their effects on reprogramming. Among DOT1L interactors, suppression of AF10 (MLLT10) via RNA interference or CRISPR/Cas9, significantly increases reprogramming efficiency. In somatic cells and induced pluripotent stem cells (iPSCs) higher order H3K79 methylation is dependent on AF10 expression. In AF10 knock-out cells, re-expression wild-type AF10, but not a DOT1L binding-impaired mutant, rescues overall H3K79 methylation and reduces reprogramming efficiency. Transcriptomic analyses during reprogramming show that AF10 suppression results in downregulation of fibroblast-specific genes and accelerates the activation of pluripotency-associated genes. Conclusions: our findings establish AF10 as a novel barrier to reprogramming by regulating H3K79 methylation and thereby sheds light on the mechanism by which cell identity is maintained in somatic cells.
Open Access
Afrotropical montane birds experience upslope shifts and range contractions along a fragmented elevational gradient in response to global warming
(Public Library of Science, 2021) Neate-Clegg, Montague H. C.; Stuart, Simon N.; Mtui, Devolent; Newmark, William D.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589
Global warming is predicted to result in upslope shifts in the elevational ranges of bird species in montane habitats. Yet few studies have examined changes over time in the elevational distribution of species along fragmented gradients in response to global warming. Here, we report on a resurvey of an understory bird community in the Usambara Mountains in Tanzania, along a forested elevational gradient that has been fragmented over the last 200 years. In 2019, we resurveyed seven sites, ranging in elevation from 360 m to 2110 m, that were originally surveyed between 1979 and 1981. We calculated differences in mean elevation and lower and upper range limits for 29 species between the two time periods and corrected for possible differences in elevation due to chance. Over four decades, we documented a significant mean upslope shift across species of 93 m. This shift was smaller than the 125 m expected shift due to local climate warming. Of the 29 focal species, 19 shifted upslope, eight downslope, and two remained unchanged. Mean upslope shifts in species were driven largely by contracting lower range limits which moved significantly upslope on average across species by 183 m, while upper range limits shifted non-significantly upslope by 72 m, leading to a mean range contraction of 114 m across species. Community composition of understory bird species also shifted over time, with current communities resembling communities found historically at lower elevations. Past forest fragmentation in combination with the limited gap-crossing ability of many tropical understory bird species are very likely important contributory factors to the observed asymmetrical shifts in lower and upper elevational range limits. Re-establishing forested linkages among the largest and closest forest fragments in the Eastern Arc Mountains are critical to permitting species to shift upslope and to reduce further elevational range contractions over time.
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; 307350
An 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.
Open Access
An LED-Based structured illumination microscope using a digital micromirror device and GPU accelerated image reconstruction
(Public Library of Science, 2022) Aydın, Musa; Doğan, Buket; Department of Physics; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Kiraz, Alper; Karalar, Elif Nur Fırat; Morova, Berna; Uysallı, Yiğit; Özgönül, Ekin; Faculty Member; Researcher; PhD Student; PhD Student; Department of Physics; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; School of Medicine; 22542; 206349; N/A; N/A; N/A
When combined with computational approaches, fluorescence imaging becomes one of the most powerful tools in biomedical research. It is possible to achieve resolution figures beyond the diffraction limit, and improve the performance and flexibility of high-resolution imaging systems with techniques such as structured illumination microscopy (SIM) reconstruction. In this study, the hardware and software implementation of an LED-based superresolution imaging system using SIM employing GPU accelerated parallel image reconstruction is presented. The sample is illuminated with two-dimensional sinusoidal patterns with various orientations and lateral phase shifts generated using a digital micromirror device (DMD). SIM reconstruction is carried out in frequency space using parallel CUDA kernel functions. Furthermore, a general purpose toolbox for the parallel image reconstruction algorithm and an infrastructure that allows all users to perform parallel operations on images without developing any CUDA kernel code is presented. The developed image reconstruction algorithm was run separately on a CPU and a GPU. Two different SIM reconstruction algorithms have been developed for the CPU as mono-thread CPU algorithm and multi-thread OpenMP CPU algorithm. SIM reconstruction of 1024 × 1024 px images was achieved in 1.49 s using GPU computation, indicating an enhancement by*28 and*20 in computation time when compared with mono-thread CPU computation and multi-thread OpenMP CPU computation, respectively.
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 Engineering
Increasing 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.
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; 111629
Many 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.
Open Access
Aurora kinase A proximity map reveals centriolar satellites as regulators of its ciliary function
(Wiley, 2021) Rauniyar, N.; Yates, J. R. III; Department of Molecular Biology and Genetics; Karalar, Elif Nur Fırat; Arslanhan, Melis Dilara; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; Graduate School of Sciences and Engineering; 206349; N/A
Aurora kinase A (AURKA) is a conserved kinase that plays crucial roles in numerous cellular processes. Although AURKA overexpression is frequent in human cancers, its pleiotropic functions and multifaceted regulation present challenges in its therapeutic targeting. Key to overcoming these challenges is to identify and characterize the full range of AURKA interactors, which are often weak and transient. Previous proteomic studies were limited in monitoring dynamic and non-mitotic AURKA interactions. Here, we generate the proximity interactome of AURKA in asynchronous cells, which consists of 440 proteins involving multiple biological processes and cellular compartments. Importantly, AURKA has extensive proximate and physical interactions to centriolar satellites, key regulators of the primary cilium. Loss-of-function experiments identify satellites as negative regulators of AURKA activity, abundance, and localization in quiescent cells. Notably, loss of satellites activates AURKA at the basal body, decreases centrosomal IFT88 levels, and causes ciliogenesis defects. Collectively, our results provide a resource for dissecting spatiotemporal regulation of AURKA and uncover its proteostatic regulation by satellites as a new mechanism for its ciliary functions.
Open Access
Avian use of agricultural areas as migration stopover sites: a review of crop management practices and ecological correlates
(Frontiers, 2021) Blount, J. David; Horns, Joshua J.; Kittelberger, Kyle D.; Neate-Clegg, Montague H. C.; Department of Molecular Biology and Genetics; Şekercioğlu, Çağan Hakkı; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; 327589
An estimated 17% of migratory bird species are threatened or near threatened with extinction. This represents an enormous potential loss of biodiversity and cost to human societies due to the economic benefits that birds provide through ecosystem services and ecotourism. Conservation of migratory bird species presents many unique challenges, as these birds rely on multiple geographically distinct habitats, including breeding grounds, non-breeding grounds, and stopover sites during migration. In particular, stopover habitats are seldom studied relative to breeding and non-breeding habitats, despite their importance as refueling stations for migratory birds. In this study, we summarize the current research on the use of temporary primary crops by birds during migration and we assess the species characteristics and agricultural practices most often associated with the use of cropland as stopover habitat. First, we conducted a systematic review of the literature to document the effects various farming practices and crop types have on the abundance and diversity of migratory birds using agricultural areas for stopovers. Second, we analyzed the ecological correlates of bird species in the Northern Hemisphere that predict which species may use these areas while migrating. We ran a GLMM to test whether primary diet, diet breadth, primary habitat, habitat breadth, or realm predicted stopover use of agricultural areas. Our review suggests that particular crop types (principally rice, corn, and sunflower), as well as farming practices that result in higher non-cultivated plant diversity, encourage the use of agricultural areas by migrating birds. We found that cropland is used as stopover habitat by bird species that can utilize a large breadth of habitats, as well as species with preferences for habitat similar in structure to agricultural areas.
Open Access
Bacterial tail anchors can target to the mitochondrial outer membrane
(BioMed Central, 2017) Department of Molecular Biology and Genetics; Lutfullahoglu-Bal, Guleycan; Keskin, Abdurrahman; Seferoğlu, Ayşe Bengisu; Dunn, Cory David; PhD Student; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Sciences
Background: During the generation and evolution of the eukaryotic cell, a proteobacterial endosymbiont was re-fashioned into the mitochondrion, an organelle that appears to have been present in the ancestor of all present-day eukaryotes. Mitochondria harbor proteomes derived from coding information located both inside and outside the organelle, and the rate-limiting step toward the formation of eukaryotic cells may have been development of an import apparatus allowing protein entry to mitochondria. Currently, a widely conserved translocon allows proteins to pass from the cytosol into mitochondria, but how proteins encoded outside of mitochondria were first directed to these organelles at the dawn of eukaryogenesis is not clear. Because several proteins targeted by a carboxyl-terminal tail anchor (TA) appear to have the ability to insert spontaneously into the mitochondrial outer membrane (OM), it is possible that self-inserting, tail-anchored polypeptides obtained from bacteria might have formed the first gate allowing proteins to access mitochondria from the cytosol. Results: Here, we tested whether bacterial TAs are capable of targeting to mitochondria. In a survey of proteins encoded by the proteobacterium Escherichia coli, predicted TA sequences were directed to specific subcellular locations within the yeast Saccharomyces cerevisiae. Importantly, TAs obtained from DUF883 family members ElaB and YqjD were abundantly localized to and inserted at the mitochondrial OM. Conclusions: Our results support the notion that eukaryotic cells are able to utilize membrane-targeting signals present in bacterial proteins obtained by lateral gene transfer, and our findings make plausible a model in which mitochondrial protein translocation was first driven by tail-anchored proteins.
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; 130295
Photovoltaic 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.
Open Access
Bidirectional optical neuromodulation using capacitive charge-transfer
(The Optical Society (OSA) Publishing, 2020) Department of Electrical and Electronics Engineering; N/A; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Melikov, Rustamzhon; Srivastava, Shashi Bhushan; Karatüm, Onuralp; Nizamoğlu, Sedat; Doğru-Yüksel, Itır Bakış; Dikbaş, Uğur Meriç; Kavaklı, İbrahim Halil; PhD Student; Researcher; PhD Student; Faculty Member; Master Student; Faculty Member; Department of Electrical and Electronics Engineering; Department of Chemical and Biological Engineering; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; N/A; N/A; N/A; 130295; N/A; N/A; 40319
Artificial control of neural activity allows for understanding complex neural networks and improving therapy of neurological disorders. Here, we demonstrate that utilization of photovoltaic biointerfaces combined with light waveform shaping can generate safe capacitive currents for bidirectional modulation of neurons. The differential photoresponse of the biointerface due to double layer capacitance facilitates the direction control of capacitive currents depending on the slope of light intensity. Moreover, the strength of capacitive currents is controlled by changing the rise and fall time slope of light intensity. This approach allows for high-level control of the hyperpolarization and depolarization of membrane potential at single-cell level. Our results pave the way toward advanced bioelectronic functionalities for wireless and safe control of neural activity.
Open Access
Biocompatible quantum funnels for neural photostimulation
(American Chemical Society (ACS), 2019) N/A; Department of Chemical and Biological Engineering; N/A; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; N/A; Jalali, Houman Bahmani; Doğru-Yüksel, Itır Bakış; Eren, Güncem Özgün; Nizamoğlu, Sedat; Karatüm, Onuralp; Melikov, Rustamzhon; Dikbaş, Uğur Meriç; Kavaklı, İbrahim Halil; Sadeghi, Sadra; Yıldız, Erdost; Ergün, Çağla; Şahin, Afsun; PhD Student; Faculty Member; PhD Student; Master Student; Faculty Member; PhD Student; PhD Student; Faculty Member; Department of Chemical and Biological Engineering; Department of Electrical and Electronics Engineering; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Sciences and Engineering; College of Engineering; College of Sciences; School of Medicine; N/A; N/A; N/A; 130295; N/A; N/A; N/A; 40319; N/A; N/A; N/A; 171267
Neural photostimulation has high potential to understand the working principles of complex neural networks and develop novel therapeutic methods for neurological disorders. A key issue in the light-induced cell stimulation is the efficient conversion of light to bioelectrical stimuli. In photosynthetic systems developed in millions of years by nature, the absorbed energy by the photoabsorbers is transported via nonradiative energy transfer to the reaction centers. Inspired by these systems, neural interfaces based on biocompatible quantum funnels are developed that direct the photogenerated charge carriers toward the bionanojunction for effective photostimulation. Funnels are constructed with indium-based rainbow quantum dots that are assembled in a graded energy profile. Implementation of a quantum funnel enhances the generated photoelectrochemical current 215% per unit absorbance in comparison with ungraded energy profile in a wireless and free-standing mode and facilitates optical neuromodulation of a single cell. This study indicates that the control of charge transport at nanoscale can lead to unconventional and effective neural interfaces.