Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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  • Conference Object
    A Carbohydrate sulfotransferase mutant zebrafish shows importance of keratan sulfate proteoglycan in skeletal structure
    (Mary Ann Liebert, 2024) Basol, M.; Ersoz, E.; Özaktaş, Helin; Cakan-Akdogan, G.
  • Book Part
    Citation - Scopus: 1
    Automated Analysis of Phase-Contrast Optical Microscopy Time-Lapse Images: Application To Wound Healing and Cell Motility Assays of Breast Cancer
    (Elsevier, 2023) Erdem, Yusuf Sait; Ayanzadeh, Aydın; Mayalı, Berkay; Balıkçı, Muhammed; Belli, Özge Nur; Uçar, Mahmut; Yalçın Özuysal, Özden; Pesen Okvur, Devrim; Önal, Sevgi; Morani, Kenan; Iheme, Leonardo Obinna; Töreyin, Behçet Uğur
    This chapter describes a workflow for analyzing phase-contrast microscopy (PCM) data from two fundamental types of biomedical assays: assays for cell motility and assays for wound healing. The workflow of the analysis is composed of the methods for acquiring, restoring, segmenting, and quantifying biomedical data. In the literature, there have been separate methods aimed at specific stages of PCM data analysis. Nonetheless, there has never been a complete workflow for all stages of analysis. This work is an innovation that proposes an end-to-end workflow for image pre-processing, deep learning segmentation, tracking, and quantification stages in cell motility and wound healing assay analyses. The findings indicate that domain knowledge can be used to make simple but significant improvements to the results of cutting-edge methods. Furthermore, even for deep learning-based methods, pre-processing is clearly a necessary step in the workflow. © 2023 Elsevier Inc. All rights reserved.
  • Review
    Citation - WoS: 9
    Citation - Scopus: 7
    Micrornas and Long Non-Coding Rnas as Novel Targets in Anti-Cancer Drug Development
    (Bentham Science Publishers, 2023) Çetinkaya, Melisa; Baran, Yusuf
    Non-coding RNAs comprise the majority of RNAs that have been transcribed from the human genome, and these non-coding RNAs have essential regulatory roles in the cellular processes. They have been discovered to influence the expression of the genes, including tumor-suppressive and oncogenes, that establish the non-coding RNAs as novel targets for anti-cancer drug development. Among non-coding RNAs, microRNAs have been extensively studied in terms of cancer biology, and some microRNA-based therapeutics have been reached in clinical studies. Even though most of the research regarding targeting non-coding RNAs for anti-cancer drug development focused on microRNAs, long non-coding RNAs have also started to gain importance as potential therapeutic targets for cancer therapy. In this chapter, the strategies and importance of targeting microRNAs and long non-coding RNAs will be described, along with the clinical studies that involve microRNA-based cancer therapeutics and preclinical studies that involve long non-coding RNA-based therapeutics. Finally, the delivery strategies that have great importance in the effective delivery of the non-coding RNA-based cancer therapeutics, hence the therapy's effectiveness, will be described.
  • Article
    Citation - WoS: 28
    Citation - Scopus: 30
    Senescence-Induced Immune Remodeling Facilitates Metastatic Adrenal Cancer in a Sex-Dimorphic Manner
    (Springer, 2023) Warde, Kate M.; Smith, Lorenzo J.; Liu, Lihua; Stubben, Chris J.; Lohman, Brian K.; Willett, Parker W.; Ammer, Julia L.; Castaneda Hernandez, Guadalupe; Imodoye, Sikiru O.; Zhang, Chenge; Jones, Kara D.; Converso Baran, Kimber; Ekiz, H. Atakan
    The mechanisms underlying the influence of aging on cancer are incompletely understood. Warde et al. establish a new model of age- and sex-dependent adrenal cancer. Their work uncovers a tumor-protective role for myeloid immune cells that is enhanced by androgens. Aging markedly increases cancer risk, yet our mechanistic understanding of how aging influences cancer initiation is limited. Here we demonstrate that the loss of ZNRF3, an inhibitor of Wnt signaling that is frequently mutated in adrenocortical carcinoma, leads to the induction of cellular senescence that remodels the tissue microenvironment and ultimately permits metastatic adrenal cancer in old animals. The effects are sexually dimorphic, with males exhibiting earlier senescence activation and a greater innate immune response, driven in part by androgens, resulting in high myeloid cell accumulation and lower incidence of malignancy. Conversely, females present a dampened immune response and increased susceptibility to metastatic cancer. Senescence-recruited myeloid cells become depleted as tumors progress, which is recapitulated in patients in whom a low myeloid signature is associated with worse outcomes. Our study uncovers a role for myeloid cells in restraining adrenal cancer with substantial prognostic value and provides a model for interrogating pleiotropic effects of cellular senescence in cancer.
  • Research Project
    Ligand kütüphanelerinin yapımında kullanılacak yeni konukçu E. coli suşlarının geliştirilmesi
    (TÜBİTAK - Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, 2005) Yenidünya, Ali Fazıl; Elmacı, Zehra Seda; Arslanoğlu, Alper
    Ligand kütüphanelerinin yapımındaki ilk adım, milyonlarca ligand varyantlarını kodlayan gen fragmanlarının, seçilmiş plazmid vektörlere total olarak klonlanmasıdır. Ligand proteinler, plazmid vektörde bulunan faj pill filament proteini ile füzyon halinde ifade edildiklerinden, konak bakteride oluşan yeni faj partiküllerinin yapısına girerler. Faj partiküllerini oluşturan proteinler de ligand DNA klonlarını içeren konak bakterinin yardımcı fajlarla (hepler-phage) süper-enfeksiyonu ile sağlanır. Ligand kütüphanelerinin zenginliği, içerdikleri farklı gen fragmanlarının sayısıyla (diversity) doğru orantılıdır. Faj displey yönteminin, henüz, kütüphane diversitesini negatif yönde etkileyebilecek bazı yönleri vardır. Bunlardan bir tanesi, süper-enfeksiyondan sonra oluşan fa partiküllerinin teorik olarak yarısının, spesifik ligand taşıdıkları halde, ligand genini taşıyan plazmidin yerine yardımcı faj genomunu paketlemiş olmalarından kaynaklanmaktadır. Bu fajlar, hem bir ligandı hemde onun genini taşıyan fajlarla seçim sırasında rekabet edemezler ve bir sonraki seçim sırasında kaybolurlar. Bu durum, herhangi bir kütüphanede en az sıklıkta temsil edilen fakat işlev bakımından büyük öneme sahip olabilecek ligandların, ardışık seçim aşamalarında kaybolmalarına neden olmaktadır. Diğer bir dezavantaj, süper-enfeksiyon sırasında veya sonrasında yardımcı faj tarafından enfekte olmuş bir bakterinin yeniden enfeksiyona uğramasıdır. Bu da; ligand taşımayan faj partiküllerinin sayıca artması nedeniyle, ligand DNA'sını taşıyan faj partiküllerinin popülasyondaki sıklığını azaltır. Faj displey yönteminde bu iki dezavantaj, faj süper-enfeksiyonundan kaynaklanmaktadır. Proje, süper-enfeksiyon sürecinin faj displey yönteminden eliminasyonunu öngörmüştür.
  • Article
    Citation - WoS: 22
    Citation - Scopus: 23
    A Single-Amino Acid Substitution in the Adaptor Lat Accelerates Tcr Proofreading Kinetics and Alters T-Cell Selection, Maintenance and Function
    (Nature Portfolio, 2023) Lo, Wan-Lin; Ekiz, Hüseyin Atakan; Kuhlmann, Miriam; Rizzuto, Gabrielle; Ekiz, H. Atakan; Kolawole, Elizabeth M.; Revelo, Monica P.; Andargachew, Rakieb
    Mature T cells must discriminate between brief interactions with self-peptides and prolonged binding to agonists. The kinetic proofreading model posits that certain T-cell antigen receptor signaling nodes serve as molecular timers to facilitate such discrimination. However, the physiological significance of this regulatory mechanism and the pathological consequences of disrupting it are unknown. Here we report that accelerating the normally slow phosphorylation of the linker for activation of T cells (LAT) residue Y136 by introducing an adjacent Gly135Asp alteration (LAT(G135D)) disrupts ligand discrimination in vivo. The enhanced self-reactivity of LAT(G135D) T cells triggers excessive thymic negative selection and promotes T-cell anergy. During Listeria infection, LAT(G135D) T cells expand more than wild-type counterparts in response to very weak stimuli but display an imbalance between effector and memory responses. Moreover, despite their enhanced engagement of central and peripheral tolerance mechanisms, mice bearing LAT(G135D) show features associated with autoimmunity and immunopathology. Our data reveal the importance of kinetic proofreading in balancing tolerance and immunity. Lo and colleagues provide evidence for the TCR kinetic proofreading model by LAT Gly135Asp alteration to reveal functional consequences of altered kinetics in TCR activation in thymic selection and mature T-cell responses.
  • Research Project
    Ms Homolog özelliğe dayalı veritabanı aramalarının kapsamının genişletilmesi
    (2012) Yılmaz, Şule; Allmer, Jens
    Proteomik, çalışılan proteinin işlevini, yerini, etkileşimi ve diğer özelliklerini inceleyen bir bilim dalıdır. Kütle spektrometresi (MS) bu alanda kullanılan bir analitik tekniktir. Bu teknik, birkaç saat içerisinde binlerce spektrumlar üretilmesine olanak sağlamaktadır. Bu alanda, temel olarak iki yaklaşım bulunmaktadır: veritabanı araması ve de novo dizileme. Veritabanı araması, bilinen bir protein dizisi söz konusu olduğunda spektrumlara tahmin atamaları yapılmasına fırsat vermektedir. Fakat tahminler, veritabanında dizinin doğru bir şekilde eklenmiş olmasına bağlıdır. Dizinin veritabanında yer almadığı durumlarda, de novo dizileme algoritmaları ile veritabanından herhangi bir yardım almadan incelenen protein hakkında sonuç elde edilebilmektedir. Fakat bu algoritmaların başarısı spektrumların kalitesine oldukça bağlıdır. Veritabanı aramalarında, hata-toleranslı tanımlamaya olanak veren bazı yöntemler bulunmaktadır. Peptit dizi etkiletleme (PDE) bu amaçla kullanılan bir tekniktir. PDE, arama alanını azaltmak amacı ile veritabanının filtrelemesinde de kullanılan kısa amino asit dizisidir. Fakat PDE’ler, öncül yon kütlesine bağlıdır ve bu yüzden öncül iyon kütlesindeki herhangi bir değişiklik PDE yaratılmasını engellemektedir. Ayrıca, veritabanında protein dizisi bulunmadığı durumlarda homoloji arama yapılması da yararlı olabilmektedir. Bu strateji, yakın türler üzerinde veritabanı aramasını olanak sağlamaktadır. Mevcut homoloji arama yöntemleri de novo dizileme algoritmalarına dayalı olarak çalışmaktadır. Fakat kullanılan de novo dizileme algoritmaları modellemede bazı matematiksel hataları içerebilmekte ve spektrumlara her zaman tahmin verememektedirler.
  • Research Project
    Sistemik Mantar İlaçlarına Karşı Gelişen İlaç Dirençlilik Mekanizmalarının Belirlenmesi
    (2015) Koç, Ahmet; Ercan, İlkcan; Işık, Çiğdem
    [No Abstract Available]
  • Book Part
    Citation - Scopus: 5
    Epitranscriptomics Changes the Play: M6a Rna Modifications in Apoptosis
    (Springer, 2022) Akçaöz, Azime; Akgül, Bünyamin
    Apoptosis is a form of programmed cell death that is essential for cellular and organismal homeostasis. Any irregularities that disturb the balance between apoptosis and cell survival have severe implications, such as improper development or life-threatening diseases. Thus, it is highly critical to maintain a proper rate of apoptosis throughout development. In fact, several complex transcriptional and posttranscriptional mechanisms exist in eukaryotes to critically regulate the rate of apoptotic processes. Recent studies suggest that not only RNA sequences but also their modifications, such as m6A methylation, play a fundamental role in these transcriptional and posttranscriptional processes. A specific set of proteins, called writer, eraser, and reader of m6A marks, modulate the rate of apoptosis by determining the m6A repertoire and the fate of certain transcripts associated with apoptosis. In this Review, we will cover the dynamic m6A RNA modifications and their impact on modulation of apoptosis.
  • Article
    Comparative Proteome Profiles of Methicillin-Resistant Staphylococcus Aureus in Response To Vanillic Acid and 2-Hydroxycinnamic Acid
    (Bentham Science Publishers, 2021) Keman, Deniz; Soyer, Ferda
    Background: The ability of Staphylococcus aureus to cause severe infections and the difficulty of the treatments due to the multiple antibiotic resistance make this bacterium a lifethreatening human pathogen. This situation necessitates the exploration of novel antimicrobial compounds with known targets on bacteria. Phenolic acids naturally produced in plants as secondary metabolites are good candidates for being alternative antimicrobials for antibiotic-resistant bacteria. Objective: Investigation of protein profile of Methicillin-Resistant S. Aureus (MRSA) in the presence of subinhibitory concentrations of phenolic acids. Methods: MRSA was subjected to subinhibitory concentrations of Vanillic Acid (VA) and 2-Hydroxycinnamic Acid (2-HCA), separately, and the proteomic analyses were carried out by using liquid chromatography coupled to mass spectrometry. Results: Both phenolic acids elicited identification of differently expressed proteins that have roles in DNA replication, repair, RNA processing and transcription, protein synthesis, maintenance of cell homeostasis, several metabolic reactions in energy, carbohydrate and lipid metabolisms and also proteins related with the virulence and the pathogenicity of MRSA when compared with the control group. The numbers of the proteins identified were 444, 375, and 426 for control, VA-treated MRSA, and 2-HCA-treated MRSA, respectively, from which 256 were shared. While VA treatment resulted in 149 unidentified MRSA proteins produced in control, 2-HCA treatment resulted in 126 unidentified proteins. Data are available via ProteomeXchange with identifier PXD016922. Conclusion: The results obtained from this study might indicate the potential targets on bacteria and the effective use of phenolic acids in the battle with antibiotic-resistant pathogens.