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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Nanoscale communication with molecular arrays in nanonetworks(Institute of Electrical and Electronics Engineers (IEEE), 2012) Galmes, Sebastia; Atakan, Barış; Akan, Özgür Barış; PhD Student; Faculty Member; College of EngineeringMolecular communication is a promising nanoscale communication paradigm that enables nanomachines to exchange information by using molecules as communication carrier. Up to now, the molecular communication channel between a transmitter nanomachine (TN) and a receiver nanomachine (RN) has been modeled as either concentration channel or timing channel. However, these channel models necessitate exact time synchronization of the nanomachines and provide a relatively low communication bandwidth. In this paper, the Molecular ARray-based COmmunication (MARCO) scheme is proposed, in which the transmission order of different molecules is used to convey molecular information without any need for time synchronization. The MARCO channel model is first theoretically derived, and the intersymbol interference and error probabilities are obtained. Based on the error probability, achievable communication rates are analytically obtained. Numerical results and performance comparisons reveal that MARCO provides significantly higher communication rate, i.e., on the scale of 100 Kbps, than the previously proposed molecular communication models without any need for synchronization. More specifically, MARCO can provide more than 250 Kbps of molecular communication rate if intersymbol time and internode distance are set to 2 mu s and 2 nm, respectively.Publication Open Access In vitro and in vivo biolasing of fluorescent proteins suspended in liquid microdroplet cavities(Royal Society of Chemistry (RSC), 2014) Jonas, Alexandr; Anand, Suman; McGloin, David; Department of Physics; Department of Chemistry; Bayraktar, Halil; Kiraz, Alper; Aas, Mehdi; Karadağ, Yasin; Manioğlu, Selen; Faculty Member; Faculty Member; PhD Student; Department of Physics; Department of Chemistry; College of Sciences; N/A; 22542; N/A; N/A; N/AFluorescent proteins are indispensable for selective, quantitative visualization of localization, dynamics, and interactions of key molecular constituents of live cells. Incorporation of fluorescent proteins into an optical cavity can lead to a significant increase in fluorescence signal levels due to stimulated emission and light amplification in the cavity, forming a laser with biological gain medium. Utilization of lasing emission from fluorescent biological molecules can then greatly enhance the performance of fluorescence-based biosensors benefiting from the high sensitivity of non-linear lasing processes to small perturbations in the cavity and the gain medium. Here we study optofluidic biolasers that exploit active liquid optical resonators formed by surface-supported aqueous microdroplets containing purified yellow fluorescent protein or a suspension of live E. coli bacterial cells expressing the fluorescent protein. We first demonstrate lasing in fluorescent protein solutions at concentrations as tow as 49 mu M. Subsequently, we show that a single fluorescent bacterial cell of micrometre size confined in a droplet-based cavity can serve as a laser gain medium. Aqueous droplet microcavities allow the maintenance of the bacterial cells under conditions compatible with unimpeded growth. Therefore, our results also suggest a direct route to microscopic sources of laser light with self-regenerating gain media.Publication Open Access 3D spatial organization and network-guided comparison of mutation profiles in Glioblastoma reveals similarities across patients(Public Library of Science, 2019) Dinçer, Cansu; Kaya, Tuğba; Tunçbağ, Nurcan; Department of Chemical and Biological Engineering; Department of Computer Engineering; Keskin, Özlem; Gürsoy, Attila; Faculty Member; Department of Chemical and Biological Engineering; Department of Computer Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Engineering; 26605; 8745Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor. Molecular heterogeneity is a hallmark of GBM tumors that is a barrier in developing treatment strategies. In this study, we used the nonsynonymous mutations of GBM tumors deposited in The Cancer Genome Atlas (TCGA) and applied a systems level approach based on biophysical characteristics of mutations and their organization in patient-specific subnetworks to reduce inter-patient heterogeneity and to gain potential clinically relevant insights. Approximately 10% of the mutations are located in "patches" which are defined as the set of residues spatially in close proximity that are mutated across multiple patients. Grouping mutations as 3D patches reduces the heterogeneity across patients. There are multiple patches that are relatively small in oncogenes, whereas there are a small number of very large patches in tumor suppressors. Additionally, different patches in the same protein are often located at different domains that can mediate different functions. We stratified the patients into five groups based on their potentially affected pathways, revealed from the patient-specific subnetworks. These subnetworks were constructed by integrating mutation profiles of the patients with the interactome data. Network-guided clustering showed significant association between each group and patient survival (P-value = 0.0408). Also, each group carries a set of signature 3D mutation patches that affect predominant pathways. We integrated drug sensitivity data of GBM cell lines with the mutation patches and the patient groups to analyze the therapeutic outcome of these patches. We found that Pazopanib might be effective in Group 3 by targeting CSF1R. Additionally, inhibiting ATM that is a mediator of PTEN phosphorylation may be ineffective in Group 2. We believe that from mutations to networks and eventually to clinical and therapeutic data, this study provides a novel perspective in the network-guided precision medicine.Publication 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; 8579This 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.Publication Open Access Detection of biological switches using the method of Groebner bases(BioMed Central, 2019) Department of Chemical and Biological Engineering; Arkun, Yaman; Faculty Member; Department of Chemical and Biological Engineering; College of Engineering; 108526Background: bistability and ability to switch between two stable states is the hallmark of cellular responses. Cellular signaling pathways often contain bistable switches that regulate the transmission of the extracellular information to the nucleus where important biological functions are executed. Results in this work we show how the method of Groebner bases can be used to detect bistability and output switchability. The method of Groebner bases can be seen as a multivariate, non-linear generalization of the Gaussian elimination for linear systems which conveniently seperates the variables and drastically simplifies the simultaneous solution of polynomial equations. A necessary condition for fixed-point state bistability is for the Grobner basis to have three distinct solutions for the state. A sufficient condition is provided by the eigenvalues of the local Jacobians. We also introduce the concept of output switchability which is defined as the ability of an output of a bistable system to switch between two different stable steady-state values. It is shown that bistability does not necessarily guarantee switchability of every state variable of the system. We further show that, for a bistable system, the necessary conditions for output switchability can be derived using the Groebner basis. The theoretical results are incorporated into an analysis procedure and applied to several systems including the AKT (Protein kinase B), RAS (Rat Sarcoma) and MAPK (Mitogen-activated protein kinase) signal transduction pathways. Results demonstrate that the Groebner bases can be conveniently used to analyze biological switches by simultaneously detecting bistability and output switchability. Conclusion: the Groebner bases provides a novel methodology to analyze bistability. Results clarify the distinction between bistability and output switchability which is lacking in the literature. We have shown that theoretically, it is possible to have an output subspace of an n-dimensional bistable system where certain variables cannot switch. It is possible to construct such systems as we have done with two reaction networks.Publication Open Access Machine learning-enabled multiplexed microfluidic sensors(American Institute of Physics (AIP) Publishing, 2020) Yetişen, Ali Kemal; N/A; Department of Mechanical Engineering; Department of Electrical and Electronics Engineering; Dabbagh, Sajjad Rahmani; Rabbi, Fazle; Doğan, Zafer; Taşoğlu, Savaş; Faculty Member; Faculty Member; Department of Mechanical Engineering; Department of Electrical and Electronics Engineering; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); KU Arçelik Research Center for Creative Industries (KUAR) / KU Arçelik Yaratıcı Endüstriler Uygulama ve Araştırma Merkezi (KUAR); Graduate School of Social Sciences and Humanities; Graduate School of Sciences and Engineering; College of Engineering; N/A; N/A; 280658; 291971High-throughput, cost-effective, and portable devices can enhance the performance of point-of-care tests. Such devices are able to acquire images from samples at a high rate in combination with microfluidic chips in point-of-care applications. However, interpreting and analyzing the large amount of acquired data is not only a labor-intensive and time-consuming process, but also prone to the bias of the user and low accuracy. Integrating machine learning (ML) with the image acquisition capability of smartphones as well as increasing computing power could address the need for high-throughput, accurate, and automatized detection, data processing, and quantification of results. Here, ML-supported diagnostic technologies are presented. These technologies include quantification of colorimetric tests, classification of biological samples (cells and sperms), soft sensors, assay type detection, and recognition of the fluid properties. Challenges regarding the implementation of ML methods, including the required number of data points, image acquisition prerequisites, and execution of data-limited experiments are also discussed.Publication Open Access Tipping the scale from disorder to alpha-helix: folding of amphiphilic peptides in the presence of macroscopic and molecular interfaces(Public Library of Science, 2015) Globisch, Christoph; Peter, Christine; N/A; Department of Mechanical Engineering; Dalgıçdır, Cahit; Sayar, Mehmet; PhD Student; Faculty Member; Department of Mechanical Engineering; Graduate School of Sciences and Engineering; College of Engineering; N/A; 109820Secondary amphiphilicity is inherent to the secondary structural elements of proteins. By forming energetically favorable contacts with each other these amphiphilic building blocks give rise to the formation of a tertiary structure. Small proteins and peptides, on the other hand, are usually too short to form multiple structural elements and cannot stabilize them internally. Therefore, these molecules are often found to be structurally ambiguous up to the point of a large degree of intrinsic disorder in solution. Consequently, their conformational preference is particularly susceptible to environmental conditions such as pH, salts, or presence of interfaces. In this study we use molecular dynamics simulations to analyze the conformational behavior of two synthetic peptides, LKKLLKLLKKLLKL (LK) and EAA LAEALAEALAE (EALA), with built-in secondary amphiphilicity upon forming an alpha-helix. We use these model peptides to systematically study their aggregation and the influence of macroscopic and molecular interfaces on their conformational preferences. We show that the peptides are neither random coils in bulk water nor fully formed alpha helices, but adopt multiple conformations and secondary structure elements with short lifetimes. These provide a basis for conformation-selection and population-shift upon environmental changes. Differences in these peptides' response to macroscopic and molecular interfaces (presented by an aggregation partner) can be linked to their inherent alpha-helical tendencies in bulk water. We find that the peptides' aggregation behavior is also strongly affected by presence or absence of an interface, and rather subtly depends on their surface charge and hydrophobicity.Publication Open Access A communication theoretical analysis of FRET-based mobile ad hoc molecular nanonetworks(Institute of Electrical and Electronics Engineers (IEEE), 2014) Kuşcu, Murat; Akan, Özgür Barış; Faculty Member; College of EngineeringNanonetworks refer to a group of nano-sized machines with very basic operational capabilities communicating to each other in order to accomplish more complex tasks such as in-body drug delivery, or chemical defense. Realizing reliable and high-rate communication between these nanomachines is a fundamental problem for the practicality of these nanonetworks. Recently, we have proposed a molecular communication method based on Forster Resonance Energy Transfer (FRET) which is a nonradiative excited state energy transfer phenomenon observed among fluorescent molecules, i.e., fluorophores. We have modeled the FRET-based communication channel considering the fluorophores as single-molecular immobile nanomachines, and shown its reliability at high rates, and practicality at the current stage of nanotechnology. In this study, for the first time in the literature, we investigate the network of mobile nanomachines communicating through FRET. We introduce two novel mobile molecular nanonetworks: FRET-based mobile molecular sensor/actor nanonetwork (FRET-MSAN) which is a distributed system of mobile fluorophores acting as sensor or actor node; and FRET-based mobile ad hoc molecular nanonetwork (FRETMAMNET) which consists of fluorophore-based nanotransmitter, nanoreceivers and nanorelays. We model the single message propagation based on birth death processes with continuous time Markov chains. We evaluate the performance of FRETMSAN and FRET-MAMNET in terms of successful transmission probability and mean extinction time of the messages, system throughput, channel capacity and achievable communication rates.Publication Open Access The structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer(Public Library of Science, 2014) Nussinov, Ruth; (TBD); Gürsoy, Attila; Özbabacan, Saliha Ece Acuner; Keskin, Özlem; Faculty Member; (TBD); The Center for Computational Biology and Bioinformatics (CCBB); College of Engineering; 8745; N/A; 26605Structural pathways are important because they provide insight into signaling mechanisms; help understand the mechanism of disease-related mutations; and help in drug discovery. While extremely useful, common pathway diagrams lacking structural data are unable to provide mechanistic insight to explain oncogenic mutations or SNPs. Here we focus on the construction of the IL-1 structural pathway and map oncogenic mutations and SNPs to complexes in this pathway. Our results indicate that computational modeling of protein-protein interactions on a large scale can provide accurate, structural atom-level detail of signaling pathways in the human cell and help delineate the mechanism through which a mutation leads to disease. We show that the mutations either thwart the interactions, activating the proteins even in their absence or stabilize them, leading to the same uncontrolled outcome. Computational mapping of mutations on the interface of the predicted complexes may constitute an effective strategy to explain the mechanisms of mutations- constitutive activation or deactivation.Publication Open Access Human cancer protein-protein interaction network: a structural perspective(Public Library of Science, 2009) Department of Computer Engineering; Department of Chemical and Biological Engineering; Kar, Gözde; Gürsoy, Attila; Keskin, Özlem; Faculty Member; Department of Computer Engineering; Department of Chemical and Biological Engineering; College of Engineering; N/A; 8745; 26605Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi-interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network). The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%). We illustrate the interface related affinity properties of two cancer-related hub proteins: Erbb3, a multi interface, and Raf1, a single interface hub. The results reveal that affinity of interactions of the multi-interface hub tends to be higher than that of the single-interface hub. These findings might be important in obtaining new targets in cancer as well as finding the details of specific binding regions of putative cancer drug candidates.