Cancer systems biology encompasses the application of systems biology approaches to cancer research, in order to study the disease as a complex adaptive system with emerging properties at multiple biological scales. Cancer systems biology represents the application of systems biology approaches to the analysis of how the intracellular networks of normal cells are perturbed during carcinogenesis to develop effective predictive models that can assist scientists and clinicians in the validations of new therapies and drugs. Tumours are characterized by genomic and epigenetic instability that alters the functions of many different molecules and networks in a single cell as well as altering the interactions with the local environment. Cancer systems biology approaches, therefore, are based on the use of computational and mathematical methods to decipher the complexity in tumorigenesis as well as cancer heterogeneity. Cancer systems biology encompasses concrete applications of systems biology ...
Hofestädt, R., and Kolchanov, N. eds. (2010). Computational Systems Biology: German/Russian Network of Computational Systems Biology. Medizinische Informatik und Bioinformatik ...
Systems Biology of Apoptosis summarizes all current achievements in this emerging field. Apoptosis is a process common to all multicellular organisms. Apoptosis leads to the elimination of cells via a complex but highly defined cellular programme. Defects in the regulation of apoptosis result in serious diseases such as cancer, autoimmunity, AIDS and neurodegeneration. Recently, a substantial step forward in understanding the complex apoptotic pathways has been made by utilising systems biology approaches. Systems biology combines rigorous mathematical modelling with experimental approaches in a closed loop cycle for advancing our knowledge about complex biological processes. In this book, the editor describes the contemporary systems biology studies devoted to apoptotic signaling and focuses on the question how systems biology helps to understand life/death decisions made in the cell and to develop new approaches to rational treatment strategies ...
Research outputs, collaborations and relationships for Institute for Integrative Systems Biology (IBIS), UL published between 1 July 2019 - 30 June 2020 as tracked by the Nature Index.
The term systems biology is now widely used and there is not one common definition of it. In reality, there are uncountable ways of understanding, explaining and applying systems biology. Concepts as represented in review articles by Hornberg et al. [7] or Bruggeman and Westerhoff [8] nicely describe what could be considered as common understanding of systems biology. In order to make clear how I understand systems biology I suggest one definition of systems biology as follows:. While traditional, reductionistic approaches investigated the property of one or of a few components (i.e. molecules) or their interaction with one or a few other molecules at the time, systems biology investigates the emergent properties of the system under investigation (e.g. organelles, cells, organs, organisms or eco systems) when multiple entities interact in networks. To do so, systems biology requires highly interdisciplinary approaches involving expertise from physics, mathematics, graph network theory and ...
Aging is a major risk factor for chronic diseases, which in turn can provide information about the aging of a biological system. This publication serves as an introduction to systems biology and its ...
Journal of Computational Systems Biology (JCSB) is an open access online journal which aims to publish peer reviewed research articles and short communications in all aspects of computational biology and bioinformatics. JCSB comprehend the broad spectrum of computational bioscience including biological databases and bioalgorithms.
2013) Delivering intellectual physical download computational systems biology inference and modelling 2016 in Russian events: a weight mass of Scottish Natural Heritage National Nature Reserves. International Research in Geographical and Environmental Education, multiperiod), 4-22. The Canadian Environmental Literacy Project( CELP).
Computational Systems Biology Lecture 2: Enzymes 1 Images from: David L. Nelson, Lehninger Principles of Biochemistry, IV Edition, Freeman ed. or under creative commons license (search for images at
Information regarding the different downstream target genes of WRKY TFs that regulate abiotic stress-induced responses is limited. Advances have, however, been made in a dehydration tolerance signaling pathway in the resurrection plant Boea hygrometrica (Wang et al. 2009). An important downstream target gene, Galactinol synthase 1 (BhGolS1), which plays a role in drought and cold tolerance (Teruaki et al. 2002) was found to be dehydration and ABA inducible. The BhGolS1 promoter contains four W boxes and chromatin immunoprecipitation showed that it is bound in vivo by the early dehydration and ABA-inducible BhWRKY1 TF (Wang et al. 2009). These observations provide direct insights into the role of a dehydration-inducible WRKY TF that interacts with a downstream target gene that plays an important role in drought responses. Recently, convincing evidence has been presented to show that AtWRKY8 functions antagonistically with its interacting partner VQ9 to modulate salinity tolerance (Hu et al. ...
The first part of this thesis focuses on the mechanisms of hormone induced Ca2+ oscillations and how these depend on fluctuations in the concentration of the Ca2+-releasing messenger, inositol 1,4,5-trisphosphate (IP3). We were able to show that IP3 oscillations greatly enhances the ability to frequency encode the hormone stimulus by Ca2+ oscillations. Two mechanisms for the generation of IP3-oscillations have been investigated, we could show that Ca2+-activation of phospholipase C is the most probable mechanism. To better understand the role of IP3-oscillations a detailed model for the phosphoinositide pathway has been developed. The model illustrates the importance of futile (de)phosphorylation cycles for regenerating phosphatidylinositol-4,5-bisphophat during stimulation, an essential property to support long-lasting Ca2+ signals. The second part of the thesis is devoted to nucleotide excision repair (NER). It is a versatile DNA repair mechanism that can remove lesions such as UV light ...
NMR spectroscopy is widely regarded as a technique that is unbiased, non-invasive and requires minimal sample preparation. These characteristics make this technique an ideal one to monitor the biological systems. In addition, NMR spectroscopy can also provide global snapshot and dynamics of complex biological systems such as cell, tissue or even an organism. This finds utility in the recently developed systems biological approaches that take holistic view of the complex biological networks rather than the conventional reductionism. Within the Biochemistry and Systems Biology group, Our lab focuses on one such complex problem that is the host-parasite interaction during infection by malarial parasite. Malaria is considered to be one of the major killers in large part of the world. We believe, systems biological approaches may provide us specific insights to the mechanism of disease progression, since this involves the joint biological network of host and the parasite. Therefore, understanding the ...
TY - JOUR. T1 - Global gene expression and systems biology analysis of bovine monocyte-derived macrophages in response to in vitro challenge with mycobacterium bovis. AU - Magee, David A.. AU - Taraktsoglou, Maria. AU - Killick, Kate E.. AU - Nalpas, Nicolas C.. AU - Browne, John A.. AU - Park, Stephen D.E.. AU - Conlon, Kevin M.. AU - Lynn, David. AU - Hokamp, Karsten. AU - Gordon, Stephen V.. AU - Gormley, Eamonn. AU - MacHugh, David E.. PY - 2012/2/22. Y1 - 2012/2/22. N2 - Background: Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cell types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in ...
Dietary methionine restriction (MR) and calorie restriction (CR) each improve metabolic health and extend life span. We used comprehensive transcriptome profiling and systems biology analysis to interrogate the unique and overlapping molecular responses in rats provided these dietary regimens for 20 mo after weaning. Microarray analysis was conducted on inguinal white adipose (IWAT), brown adipose tissue (BAT), liver, and skeletal muscle. Compared to controls, CR-induced transcriptomic responses (absolute fold change ≥1.5 and P≤0.05) were comparable in IWAT, BAT, and liver (~800 genes). MR-induced effects were largely restricted to IWAT and liver (~2400 genes). Pathway enrichment and gene-coexpression analyses showed that induction of fatty acid synthesis in IWAT was common to CR and MR, whereas immunity and proinflammatory signaling pathways were specifically down-regulated in MR-treated IWAT and liver (FDR≤0.07-0.3). BAT demonstrated consistent down-regulation of PPAR-signaling under CR ...
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models,
Complex diseases, such as Type 2 Diabetes, are generally caused by multiple factors, which hamper effective drug discovery. To combat these diseases, combination regimens or combination drugs provide an alternative way, and are becoming the standard of treatment for complex diseases. However, most of existing combination drugs are developed based on clinical experience or test-and-trial strategy, which are not only time consuming but also expensive. In this paper, we presented a novel network-based systems biology approach to identify effective drug combinations by exploiting high throughput data. We assumed that a subnetwork or pathway will be affected in the networked cellular system after a drug is administrated. Therefore, the affected subnetwork can be used to assess the drugs overall effect, and thereby help to identify effective drug combinations by comparing the subnetworks affected by individual drugs with that by the combination drug. In this work, we first constructed a molecular interaction
We outline a computationally inferred model of the regulatory network of Populus leaves, and show how treating genes as interacting, rather than individual, entities identifies new regulators compared to traditional genomics analysis. Although systems biology models should be used with care considering the complexity of regulatory programs and the limitations of current genomics data, methods describing interactions can provide hypotheses about the underlying cause of emergent properties and are needed if we are to identify target genes other than those constituting the low hanging fruit of genomic analysis.. ...
npj Systems Biology and Applications is a new open-access, online only multi- and interdisciplinary journal dedicated to publishing the finest research on the Systems Biology and related research to that System Biological approach is applied.
npj Systems Biology and Applications is a new open-access, online only multi- and interdisciplinary journal dedicated to publishing the finest research on the Systems Biology and related research to that System Biological approach is applied.
Current research interests: Metabolomics. Ricks research goals focus on the systems biology investigations of microbial and mammalian systems, specifically the application of metabolomics to these disciplines and the development of analytical instrumentation and methodologies to fulfill these goals. Metabolomics is focussed on the holistic and data-driven investigation of the quantitative collection of low molecular weight organic and inorganic compounds present in biological systems. This collection of endogenous and exogenous metabolites is defined as the metabolome. Endogenous metabolites can be biochemically synthesized or catabolised within the system and exogenous metabolites are acquired from the external environment (for example, food nutrients and drugs) or from co-habiting species (for example, gut microbiome). A range of experimental strategies are employed to investigate the metabolome including metabolic profiling (untargeted analysis), targeted analysis and metabolite ...
Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response experiments (SRE) have been used to gain a deeper insight into the details of biochemical mechanisms underlying cell life and functioning. Optimisation of the input time-profile, however, still remains a major area of research due to the complexity of the problem and its relevance for the task of information retrieval in systems biology-related experiments. We have addressed the problem of quantifying the information associated to an experiment using the Fisher Information Matrix and we have proposed an optimal experimental design
Ali Ebrahim, Eivind Almaas, Eugen Bauer, Aarash Bordbar, Anthony P. Burgard, Roger L. Chang, Andreas Dräger, Iman Famili, Adam M. Feist, Ronan M. T. Fleming, Stephen S. Fong, Vassily Hatzimanikatis, Markus J. Herrgard, Allen Holder, Michael Hucka, Daniel Hyduke, Neema Jamshidi, Sang Yup Lee, Nicolas Le Novère, Joshua A. Lerman, Nathan E. Lewis, Ding Ma, Radhakrishnan Mahadevan, Costas Maranas, Harish Nagarajan, Ali Navid, Jens Nielsen, Lars K. Nielsen, Juan Nogales, Alberto Noronha, Csaba Pal, Bernhard O. Palsson, Jason A. Papin, Kiran R. Patil, Nathan D. Price, Jennifer L. Reed, Michael Saunders, Ryan S. Senger, Nikolaus Sonnenschein, Yuekai Sun, and Ines Thiele. Do Genome-scale Models Need Exact Solvers or Clearer Standards? Molecular Systems Biology, 11(10), October 2015. [ DOI , link , pdf ...
There has been one iteration of the M. barkeri reconstruction and model published in Molecular Systems Biology in early 2006.. We have the following information available:. ...
Title:In Silico Systems Pharmacology to Assess Drugs Therapeutic and Toxic Effects. VOLUME: 22 ISSUE: 46. Author(s):Alejandro Aguayo-Orozco, Karine Audouze, Soren Brunak and Olivier Taboureau. Affiliation:Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen. Keywords:Systems pharmacology, biological network, drug, protein-protein interactions, pathways, gene expression, pharmacogenomics, toxicity.. Abstract:For many years, the one target, one drug paradigm has been the driving force behind developments in pharmaceutical research. With the recent advances in molecular biology and genomics technologies, the focus is shifting toward drug-holistic systems based approaches (i.e. systems pharmacology). The integration of large and diverse amount of data from chemistry and biology coupled with the development and the application of network-based approaches to cope with these data is the next paradigm of drug discovery. ...
Systems Biology: Neurobiology - University of Toronto. The new Department of Cell and Systems Biology at the University of Toronto invites applications for a tenure track faculty position to be appointed at the Assistant Professor level in the field of Systems Biology - Neurobiology to begin July 1, 2008.. We particularly encourage candidates to apply who have demonstrated excellence in addressing fundamental questions in neurobiology using high-throughput approaches or gene/protein network analyses with bioinformatics, genomic, proteomic, electrophysiological, or imaging tools. Our vision is to advance Systems-wide analyses in Neurobiology which complement existing strengths in the department (www.csb.utoronto.ca).. Candidates should have at least two years of research experience beyond their doctoral degree. In addition to pursuing a vigorous, internationally recognized research program, the successful candidate will contribute to undergraduate and graduate teaching in the molecular life ...
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Plant carbohydrate metabolism comprises numerous metabolite interconversions, some of which form cycles of metabolite degradation and re-synthesis and are thus referred to as futile cycles. In this study, we present a systems biology approach to analyse any possible regulatory principle that operates such futile cycles based on experimental data for sucrose (Scr) cycling in photosynthetically active leaves of the model plant Arabidopsis thaliana. Kinetic parameters of enzymatic steps in Scr cycling were identified by fitting model simulations to experimental data. A statistical analysis of the kinetic parameters and calculated flux rates allowed for estimation of the variability and supported the predictability of the model. A principal component analysis of the parameter results revealed the identifiability of the model parameters. We investigated the stability properties of Scr cycling and found that feedback inhibition of enzymes catalysing metabolite interconversions at different steps of the cycle
Although gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, schizophrenia, and Tourette disorder, has accelerated, resulting in a large number of molecular clues, it has proven difficult to generate specific hypotheses without the cor …
MicroRNAs (miRNAs) are non-coding small RNA molecules that regulate the differential expression of genes. The expression of miRNAs is dysregulated in various types of cancers,including Gastric Cancer (GC), and has both prognostic and diagnostic potential. To interpret the role of miRNA expression in GC, we evaluated the expression profile using high-throughput miRNA array followed by in-depth systems biological analyses. Total RNA was isolated from 34 GC patients and 15 normal controls and hybridised and differentially expressed miRNAs in GC compared to normal controls were analysed. A total of 250 miRNAs were found to be differentially expressed in GC with a fold change ranging from + 2.5984 to – 3.5271 compared to normal gastric tissues. The differentially expressed miRNAs were further subjected to Ingenuity Pathway Analysis to understand the modulation of cellular and molecular functions and associated physiological system development and functions in GC. The Oncomirs such as miR-155-5p, miR-17
The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac
TY - JOUR. T1 - Investigating cholesterol metabolism and ageing using a systems biology approach. AU - Morgan, A.E.. AU - Mooney, Kathleen. AU - Wilkinson, S. J.. AU - Pickles, N.A.. PY - 2016/11/2. Y1 - 2016/11/2. N2 - CVD accounted for 27 % of all deaths in the UK in 2014, and was responsible for 1·7 million hospital admissions in 2013/2014. This condition becomes increasingly prevalent with age, affecting 34·1 and 29·8 % of males and females over 75 years of age respectively in 2011. The dysregulation of cholesterol metabolism with age, often observed as a rise in LDL-chol- esterol, has been associated with the pathogenesis of CVD. To compound this problem, it is estimated by 2050, 22 % of the worlds population will be over 60 years of age, in culmin- ation with a growing resistance and intolerance to pre-existing cholesterol regulating drugs such as statins. Therefore, it is apparent research into additional therapies for hypercholes- terolaemia and CVD prevention is a growing necessity. ...
NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Systems Biology Approaches to Alzheimers Disease Using Non-mammalian Laboratory Animals (R01) RFA-AG-17-057. NIA
Fingerprint Dive into the research topics of Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD. Together they form a unique fingerprint. ...
Growth is a fundamental process of life. Growth requirements are well-characterized experimentally for many microbes; however, we lack a unified model for cellular growth. Such a model must be predictive of events at the molecular scale and capable of explaining the high-level behavior of the cell as a whole. Here, we construct an ME-Model for Escherichia coli-a genome-scale model that seamlessly integrates metabolic and gene product expression pathways. The model computes ∼80% of the functional proteome (by mass), which is used by the cell to support growth under a given condition. Metabolism and gene expression are interdependent processes that affect and constrain each other. We formalize these constraints and apply the principle of growth optimization to enable the accurate prediction of multi-scale phenotypes, ranging from coarse-grained (growth rate, nutrient uptake, by-product secretion) to fine-grained (metabolic fluxes, gene expression levels). Our results unify many existing ...
All biological interactions, whether they take place on a molecular, organism or ecosystem scale, are part of complex dynamical systems. Understanding the behaviour of these systems lies at the heart of many key challenges in biological research. In this module you will have the opportunity to develop and investigate mathematical models of biological systems. You will learn techniques to construct, implement and analyse interaction networks using the Python programming language. Research in the field of Systems Biology is highly interdisciplinary. It often involves biologists working with colleagues from the fields of physics, engineering, mathematics and computer science. Consequently this module encourages participation from any interested science or engineering student. ...
Systems Biology is the application of computational modelling and simulation to complex systems in biology. Examples include biochemical pathways, metabolic processes, protein complexes and information processing, genetic networks, self-organising systems, neuronal networks and cell-cell communication. This course will focus on the level of molecular and genetic systems and simulations ...
Linux For Linux, its zip file should be extracted into your $HOME/.taverna-1.6.2/lib folder. Your Taverna runme.sh script should then be edited with the text highlighted in bold as follows: (..) # Load customised properties if they exist if [ -f $TAVERNA_HOME/custom.sh ] ; then source $TAVERNA_HOME/custom.sh fi #Set to $TAVERNA_HOME/lib for shared installation LIB_PATH=$HOME/.taverna-1.6.2/lib LD_LIBRARY_PATH=$LIB_PATH export LD_LIBRARY_PATH ARGS=-Djava.library.path=$LIB_PATH java $ARGS -jar $TAVERNA_HOME/taverna-bootstrap-1.6.2.0.jar [email protected] MacOS X For those people using MacOS X, the libsbml native libraries should be placed in the same directory where your Taverna application bundle resides. So for example, if your Taverna application bundle is in /Applications/Taverna-1.6.2/Taverna.app then the libxerces-c.27.dylib, libsbml.dylib and libsbmlj.jnilib files should be placed there. In constrast, the libsbml jar file should be placed in Tavernas lib folder which is found at ...
Modeling drug- and chemical-induced hepatotoxicity with systems biology approaches. Melvin Andersen, M Andersen, Sudin Bhattacharya, S Bhattacharya, Brett Howell, B Howell, Patrick McMullen, P McMullen, Lisl Shoda, L Shoda, Scott Siler, S Siler, Paul Watkins, P Watkins, Jeffrey Woodhead, J Woodhead, Courtney Woods, C Woods, Yuching Yang, Y Yang, Qiang Zhang, Q Zhang (2012). Frontiers in Physiology, 3.. Low-level arsenic impairs glucose-stimulated insulin secretion in pancreatic beta cells: Involvement of cellular adaptive response to oxidative stress. Melvin Andersen, Sheila Collins, Jingqi Fu, Jingbo Pi, Guifan Sun, Victoria Wong, Courtney Woods, Einav Yehuda-Shnaidman, Qiang Zhang (2010). Environmental Health Perspectives, 118(6), 864-870.. A systems biology perspective on Nrf2-mediated antioxidant response. Melvin Andersen, Jingbo Pi, Courtney Woods, Qiang Zhang (2010). Toxicology and Applied Pharmacology, 244(1), 84-97.. Dose-dependent transitions in Nrf2-mediated adaptive response and ...
The main focus of the research in the laboratory is currently split into two major directions which are apparently distinct from each other with respect to the biological systems involved, their relation to the human disease, and experimental models used. However, the main idea underlying both directions is conceptually the same - to understand how endocytosis and post-endocytic trafficking regulates function(s) of the transmembrane proteins, such as receptors and transporters. In particular, we aim at elucidating the molecular mechanisms of endocytosis of growth factor receptors using a prototypic member of the family, epidermal growth factor (EGF) receptor, and analysis of the role of endocytosis in spatial and temporal regulation of signal transduction by the EGF receptor. In the second direction, we would like to elucidate the role of trafficking processes in the regulation of dopaminergic neurotransmission by the plasma membrane dopamine transporter (DAT). By understanding how DAT activity ...
Within his laboratory, Dr. Wells and his research team are aiming to gain a better understanding of cells respond to their local environment. Due to the widespread implications of such research, Dr. Wells has been featured in several publications. Ultimately, the importance of his research flows from the provision of reinforcing insights and novel avenues for exploration into the basic signaling pathways, as well as functioning of entire organisms. Currently, Dr. Wells is concentrating his research efforts towards gaining further knowledge of the conditions of dysregulated (tumor dissemination and chemoresistance of tumors) and orchestrated (wound healing and organogenesis) responses.. ...
Congratulations to Dr. Cecilia Lo and Dr. Michael Tsang on their recently funded NIH administrative supplement, Assaying Heterotaxy Patient Genes in a Cilia Motility and Left-Right Patterning. This project will examine whether expression of the RCV can rescue the HTX phenotype elicited by MO gene knockdown in the zebrafish embryo.
Prepare for the conference with access to impactful genomics and systems biology articles, published across the AACR journals.. The field of cancer systems biology has emerged to address the increasing challenge of cancer as a complex, multifactorial disease using sophisticated model-based approaches, ranging from relatively coarse genome-wide regulatory and signaling networks to detailed kinetic models of key pathways. These networks and pathways are responsible for implementing cancer-relevant mechanisms and for processing aberrant signals from the spectrum of somatic mutations and heritable variants that contribute to tumor initiation, progression, and drug sensitivity. The ability to assemble and interrogate such cancer models is the direct result of the availability of large sample-matched collections of molecular profiles from thousands of human malignancies, as made available by large consortia, such as TCGA, ICG, and TARGET, among others. This AACR Special Conference complements and ...
Hepatitis C virus (HCV) infection is a worldwide healthcare problem; however, traditional treatment methods have failed to cure all patients, and HCV has developed resistance to new drugs. Systems biology-based analyses could play an important role in the holistic analysis of the impact of HCV on hepatocellular metabolism. Here, we integrated HCV assembly reactions with a genome-scale hepatocyte metabolic model to identify metabolic targets for HCV assembly and metabolic alterations that occur between different HCV progression states (cirrhosis, dysplastic nodule, and early and advanced hepatocellular carcinoma (HCC)) and healthy liver tissue. We found that diacylglycerolipids were essential for HCV assembly. In addition, the metabolism of keratan sulfate and chondroitin sulfate was significantly changed in the cirrhosis stage, whereas the metabolism of acyl-carnitine was significantly changed in the dysplastic nodule and early HCC stages. Our results explained the role of the upregulated ...
In Escherichia coli (E. coli), the oxidative branch of the pentose phosphate pathway (oxPPP) is one of the major sources of NADPH when glucose is the sole carbon nutrient. However, unbalanced NADPH production causes growth impairment as observed in a strain lacking phosphoglucoisomerase (Δpgi). In this work, we studied the metabolic response of this bacterium to the replacement of its glucose-6-phosphate dehydrogenase (G6PDH) by a NADH-producing variant. The homologous enzyme from Leuconostoc mesenteroides was studied by molecular dynamics and site-directed mutagenesis to obtain the NAD-preferring LmG6PDHR46E,Q47E. Through homologous recombination, the zwf loci (encoding for G6PDH) in the chromosomes of wild type (wt) and Δpgi E. coli strains were replaced by DNA encoding for LmG6PDHR46E,Q47E. Contrary to the predictions of a Robustness Analysis performed by flux balances simulation, the replacements caused a substantial effect on the growth rates, increasing 59% in the Δpgi strain, while ...
Biomolecular nuclear magnetic resonance spectroscopy (NMR) is a very versatile technique that can be used to determine the three dimensional structures of proteins, DNA, RNA, oligosaccharides and small molecules. It can also be used to study conformational changes, intermolecular interactions (both strong and weak), and molecular motion on many timescales in solution. NMR is widely used in metabolomics studies. (and enquiries for this type of application should be directed to Glasgow Polyomics) Solution state NMR complements the other techniques, such as circular dichroism and X-ray crystallography, available in the facility.. Generally, biomacromolecular NMR samples should be prepared with highly purified material, often isotopically labelled with 15N, 13C and even 2H, but NMR has been used e.g. to study proteins in living cells, and ligand-receptor interactions where the receptor comprises an un-purified membrane preparation.. Some guidance on typical sample requirements are given below, but ...
Walter Kolch is Director of Systems Biology Ireland at University College Dublin. A leading international proponent of precision medicine, Kolch originally trained as a clinician, subsequently working in the pharmaceutical industry, research institutes, and academia. He is internationally recognised for his cutting-edge research using systems approaches to understand signalling networks, and is ranked 3rd in the world in precision medicine, 8th in personalised medicine, and amongst the worlds top 50 in proteomics, systems biology, and signal transduction (Google Scholar). Through his leading involvement in pan-European strategic initiatives including Coordinating Action Systems Medicine, Infrastructure for Systems Biology Europe, and the ELIXIR research infrastructure for life science information, Kolch has played a central role in the development of precision medicine policy and funding at both national and international level.. Kolch has designed, developed and coordinated innovative systems ...
TY - JOUR. T1 - Hematopoiesis and its disorders. T2 - A systems biology approach. AU - Whichard, Zakary L.. AU - Sarkar, Casim A.. AU - Kimmel, Marek. AU - Corey, Seth J.. N1 - Copyright: Copyright 2010 Elsevier B.V., All rights reserved.. PY - 2010/3/25. Y1 - 2010/3/25. N2 - Scientists have traditionally studied complex biologic systems by reducing them to simple building blocks. Genome sequencing, high-throughput screening, and proteomics have, however, generated large datasets, revealing a high level of complexity in components and interactions. Systems biology embraces this complexity with a combination of mathematical, engineering, and computational tools for constructing and validating models of biologic phenomena. The validity of mathematical modeling in hematopoiesis was established early by the pioneering work of Till and McCulloch. In reviewing more recent papers, we highlight deterministic, stochastic, statistical, and network-based models that have been used to better understand a ...
Heat stroke (HS) is a life-threatening illness induced by prolonged exposure to a hot environment that causes central nervous system abnormalities and severe hyperthermia. There is a critical military medical need to identify biomarkers, risk factors & intervention strategies to decrease heat injury/stroke (HI/S) susceptibility. Current data suggest that the pathophysiological responses to heatstroke may not be due to the immediate effects of heat exposure per se but the result of a systemic inflammatory response syndrome (SIRS) that ensues following thermal injury. Recent evidence suggests that prior infection (viral & bacterial) or prior heat injury increases Warfighter susceptibility to HI/S by deactivating molecular inflammatory mechanisms that protect against multi-organ damage & failure. Exploiting a Systems Biology approach - which focuses on the complex interactions in biological systems - can help to understand the role of cytokines in the thermoregulatory and inflammatory responses to ...
Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach. We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D.E.S.I.R. longitudinal study. The effect of the number of copies of AMY1A (encoding AMY1) or AMY2A (encoding AMY2) measured through droplet digital PCR was then analyzed on the same parameters in the same study. A Mendelian randomization analysis was also performed. We subsequently assessed the association between AMY1A copy number and obesity risk in two case-control studies (5000 samples in total). Finally, we assessed the association between body mass index (BMI)-related plasma metabolites
Background: Salivary (AMY1) and pancreatic (AMY2) amylases hydrolyze starch. Copy number of AMY1A (encoding AMY1) was reported to be higher in populations with a high-starch diet and reduced in obese people. These results based on quantitative PCR have been challenged recently. We aimed to re-assess the relationship between amylase and adiposity using a systems biology approach. Methods: We assessed the association between plasma enzymatic activity of AMY1 or AMY2, and several metabolic traits in almost 4000 French individuals from D.E.S.I.R. longitudinal study. The effect of the number of copies of AMY1A (encoding AMY1) or AMY2A (encoding AMY2) measured through droplet digital PCR was then analyzed on the same parameters in the same study. A Mendelian randomization analysis was also performed. We subsequently assessed the association between AMY1A copy number and obesity risk in two case-control studies (5000 samples in total). Finally, we assessed the association between body mass index ...
The Plant Science Group (PSG) maintains a broad interest in understanding how plant growth and development is regulated by environmental stimuli and how plants cope with a changing environment. Our research focuses on identifying the molecular mechanisms underlying physiological and developmental adaptation to environmental cues, such as light quality and day length, as well as environmental stress factors such as drought, high temperatures and salinity.. Our aim is to gain fundamental insights into the cellular and molecular mechanisms of plant growth and development, which determine survival in natural ecosystems and yield and quality traits in agriculture. Plant performance is intricately tied to photosynthetic efficiency, water usage and mineral uptake. Increasing crop productivity will depend on modulating such processes if we are to offer new strategies to meet the growing demand for energy and food security.. Our research also employs synthetic biology and systems approaches to tackle ...
Scientists from the Icahn School of Medicine at Mount Sinai, the University of California, San Francisco, and Harvard Medical School used a rigorous study design to assess the biological impact of meditation compared to vacation. They examined the effect of meditation on gene expression patterns in both novice and regular meditators. The researchers found that a resort vacation provides a strong and immediate impact on molecular networks associated with stress and immune pathways, in addition to short- term improvements in well-being, as measured by feelings of vitality and distress. A meditation retreat, for those who already used meditation regularly, was associated with molecular networks characterized by antiviral activity. The molecular signature of long-term meditators was distinct from the non-meditating vacationers. The study was published today in Springer Natures journalTranslational Psychiatry ...
The emergence of Populus as a model system for tree biology continues to be driven by a community of scientists dedicated to developing the resources needed to undertake genetic and functional genomic studies in this genus. As a result, understanding the molecular processes that underpin the growth and development of cottonwood, aspen, and hybrid poplar has steadily increased over the last several decades. Recently, our ability to examine the basic mechanisms whereby trees respond to a changing climate and resource limitations has benefitted greatly from the sequencing of the P. trichocarpa genome. This landmark event has laid a solid foundation upon which tree biologists can now explore the genome-wide effects of temperature, water and nutrient limitations on processes that govern the growth and development of some of the longest living and tallest growing organisms on Earth. Although the challenges likely to be encountered by scientists who work with trees are many, recent literature provides ...
Contact: Dr. Douglas Sheeley, 301-451-6446, [email protected] VII. Presentation: Analysis of the National Centers for Systems Biology Program , [PDF, 668KB]. The National Centers for Systems Biology (NCSB) program was established by NIGMS in 2002 to facilitate pioneering research in systems biology and to stimulate the field as a whole. In 2014, NIGMS initiated an analysis of the NCSB program to better understand whether the program has met its goals, to assess the programs effectiveness in promoting systems biology research and to view the current state of maturity for systems biology as a field. Dr. Andrew Miklos of the NIGMS Office of Program Planning, Analysis, and Evaluation presented a brief overview of the types of data made available for consideration to the assessment panel of subject matter experts serving as a working group of Council.. Contact: Dr. Andrew Miklos, 301-451-4645, [email protected] VIII. Presentation: Assessment and Recommendations for the National Centers for ...
The Systems Biology for Infectious Diseases Research program was established by the U.S. National Institute of Allergy and Infectious Diseases to investigate host-pathogen interactions at a systems level. This program generated 47 transcriptomic and proteomic datasets from 30 studies that investigate in vivo and in vitro host responses to viral infections. Human pathogens in the Orthomyxoviridae and Coronaviridae families, especially pandemic H1N1 and avian H5N1 influenza A viruses and severe acute respiratory syndrome coronavirus (SARS-CoV), were investigated. Study validation was demonstrated via experimental quality control measures and meta-analysis of independent experiments performed under similar conditions. Primary assay results are archived at the GEO and PeptideAtlas public repositories, while processed statistical results together with standardized metadata are publically available at the Influenza Research Database (www.fludb.org) and the Virus Pathogen Resource (www.viprbrc.org). As ...
Systems biology research is the study of genes and proteins as an interconnected networks series of interconnected networks and pathways. UNSW adopts a holistic approach to build a molecular profile of an organism.
Basler, G.; Grimbs, S.; Selbig, J.; Nikoloski, Z.: Thermodynamic landscapes of randomized large-scale metabolic networks. In: 7th International Workshop on Computational Systems Biology, WCSB 2010, pp. 23 - 26 (Eds. Nykter, M.; Ruusuvuori, P.; Carlberg, C.; Yli-Harja, O.). 7th International Workshop on Computational Systems Biology, WCSB 2010, Luxembourg, LUX. Tampere International Center for Signal Processing (2010 ...
Basler, G.; Grimbs, S.; Selbig, J.; Nikoloski, Z.: Thermodynamic landscapes of randomized large-scale metabolic networks. In: 7th International Workshop on Computational Systems Biology, WCSB 2010, S. 23 - 26 (Hg. Nykter, M.; Ruusuvuori, P.; Carlberg, C.; Yli-Harja, O.). 7th International Workshop on Computational Systems Biology, WCSB 2010, Luxembourg, LUX. Tampere International Center for Signal Processing (2010 ...
The Human Genome Project has catalyzed the emergence of a new approach to biology termed systems biology. Systems biology analyzes all the interrelationships of the elements in a biological system, rather than studying them one at a time, as has been the modus operandi in biology for the past 30 years. This systems approach has also emerged in the context of the view biology
This thesis addresses the problem of collaboration among experimental biologists and modelers in the study of systems biology by using ontology and Semantic Web Services techniques. Modeling in systems biology is concerned with using experimental information and mathematical methods to build quantitative models across different biological scales. This requires interoperation among various knowledge sources and services. Ontology and Semantic Web Services potentially provide an infrastructure to meet this requirement. In our study, we propose an ontology-centered framework within the Semantic Web infrastructure that aims at standardizing various areas of knowledge involved in the biological modeling processes. In this framework, first we specify an ontology-based meta-model for building biological models. This meta-model supports using shared biological ontologies to annotate biological entities in the models, allows semantic queries and automatic discoveries, enables easy model reuse and ...
Dr. Kretzler is the Warner-Lambert/Parke-Davis Professor of Internal Medicine/Nephrology and Computational Medicine and Bioinformatics. The overarching goal of his research is to define chronic organ dysfunction in mechanistic terms and use this knowledge for targeted therapeutic interventions. To reach this goal he has developed a translational research pipeline centered on integrated systems biology analysis of renal disease.. He leads the U54 Nephrotic Syndrome Research Network (Neptune) in the Rare Disease Clinical Research Network II, is a Principle Investigator (PI) of the Coordinating center of the CureGN research network, the Director of the Applied Systems Biology Core, PI in the R24 Integrated Systems Biology Approach to Diabetic Microvascular Complications and site PI in the NIH Acceleration of Medicine (AMP) program in lupus.. He has 20 years of experience in integration of bioinformatics, molecular and clinical approaches in more than 210 publications. He has a track record on ...
This book addresses the most recent advances in the transport of proteins across a variety of biological membranes. In addressing this topic, this volume includes several new twists not previously addressed in the literature. In the last few years, the study of protein translocation has been revolutionized by the availability of structural information on many of the components and complexes involved in the process. Unlike earlier books written on protein translocation, this volume considers these advances. In addition, several chapters discuss facets of protein translocation from a systems biology perspective, considered by many to be the next paradigm for biological study. Readers of this book will come away with a deeper understanding of the problems facing researchers of protein translocation and see how the most modern biological techniques and approaches are being recruited to answer those questions. The chapters are also written such that problems awaiting future investigation are clearly ...
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Jede Zelle des Säugetierorganismus benötigt Eisen als Spurenelement für zahlreiche oxidativ-reduktive Elektronentransfer-Reaktionen und für Transport und Speicherung von Sauerstoff. Der Organismus unterhält daher ein komplexes Regulationsnetzwerk für die Aufnahme, Verteilung und Ausscheidung von Eisen. Die intrazelluläre Regulation in den verschiedenen Zelltypen des Körpers ist mit einer globalen hormonellen Signalstruktur verzahnt. Sowohl Eisenmangel wie Eisenüberschuss sind häufige und ernste menschliche Krankheitsbilder. Sie betreffen jede Zelle, aber auch den Organismus als Ganzes. In dieser Dissertation wird ein mathematisches Modell des Eisenstoffwechsels der erwachsenen Maus vorgestellt. In ihm wird die Flussbilanz des Eisens in den wichtigsten Zelltypen in Form von transmembranalen und intrazellulären kinetischen Gleichungen dargestellt, und es werden diese Zellmodelle mit dem zentralen Eisenaustausch-Kompartiment (Blutplasma) des Körpers integriert. Der Eisenstatus wird ...
In combination with the major disease oriented programs of the MDC, Medical Systems Biology is an essential strategic and overarching component of the scientific profile of the MDC: the Berlin Institute for Medical Systems Biology (BIMSB) was launched in 2008. The scientific concept was initiated by Nikolaus Rajewsky, who is now leading the program and its further developments.
Using published dairy cattle liver transcriptomics dataset along with novel blood biomarkers of liver function, metabolism, and inflammation we have attempted an integrative systems biology approach applying the classical functional enrichment analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA), and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA). Transcriptome data was generated from experiments evaluating the impact of prepartal plane of energy intake [overfed (OF) or restricted (RE)] on liver of dairy cows during the peripartal period. Blood biomarkers uncovered that RE vs. OF led to greater prepartal liver distress accompanied by a low-grade inflammation and larger proteolysis (i.e., higher haptoglobin, bilirubin, and creatinine). Post-partum the greater bilirubinaemia and lipid accumulation in OF vs. RE indicated a large degree of liver distress. The re-analysis of microarray data revealed that expression of ,4,000 genes was affected by diet x ...
프로토콜은 인간 배아 줄기 세포 및 사체 연구에 기초하여 두 개의 시험관 발생 독성 시험 시스템 (UKK 및 UKN1)를 설명한다. 테스트 시스템은 인간 발생 독성 위험을 예측하고, 동물 연구, 비용 및 화학 물질의 안전성...
The Bioinformatics and Computational Biology graduate program emphasizes interdisciplinary training in nine related areas of focus: Bioinformatics, Computational Molecular Biology, Structural and Functional Genomics, Macromolecular Structure and Function, Metabolic and Developmental Networks, Integrative Systems Biology, Information Integration and Data Mining, Biological Statistics, and Mathematical Biology ...
Sexually transmitted infections (STIs) unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome
Nonalcoholic fatty liver disease (NAFLD) comprises a broad spectrum of disease states ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). As a result of increases in the prevalences of obesity, insulin resistance, and hyperlipidemia, the number of people with hepatic steatosis continues to increase. Differences in susceptibility to steatohepatitis and its progression to cirrhosis have been attributed to a complex interplay of genetic and external factors all addressing the intracellular network. Increase in sugar or refined carbohydrate consumption results in an increase of insulin and insulin resistance that can lead to the accumulation of fat in the liver. Here we demonstrate how a multidisciplinary approach encompassing cellular reprogramming, transcriptomics, proteomics, metabolomics, modeling, network reconstruction and data management can be employed to unveil the mechanisms underlying the progression of steatosis. Proteomics revealed reduced AKT/mTOR signaling in fibroblasts
Institute for Systems Biology Appoints Pioneer in Systems Genetics to Leadership Role Joseph Nadeau Named as Director of Research and Academic Affairs SEATTLE--(BUSINESS WIRE)--The Institute for
The combination of microfluidic cell trapping devices with ion mobility-mass spectrometry offers the potential for elucidating in real time the dynamic responses of small populations of cells to paracrine signals, changes in metabolite levels and delivery of drugs and toxins. Preliminary experiments examining peptides in methanol and recording the interactions of yeast and Jurkat cells with their superfusate have identified instrumental set-up and control parameters and online desalting procedures. Numerous initial experiments demonstrate and validate this new instrumental platform. Future outlooks and potential applications are addressed, specifically how this instrumentation may be used for fully automated systems biology studies of the significantly interdependent, dynamic internal workings of cellular metabolic and signalling pathways.
The application of both pathway (Cagnin et al, 2009) and ad hoc (Skogsberg et al, 2008) network analysis has facilitated extraction of biologically meaningful information from microarray messenger RNA (mRNA) studies of atherosclerotic plaques. Such studies are critical in that they analyse disease‐relevant tissue [e.g. whole mouse aorta (Skogsberg et al, 2008) or human coronary and carotid arteries (Cagnin et al, 2009)] but they pose numerous analysis challenges. For example, the lesion samples contain a mix of cell types obtained at a fixed time point. These studies allow the construction of a parts list of molecules that may participate in the process-which is extremely useful in the interpretation and analysis of complementary in vitro studies. However, to go beyond such lists requires the application of network analysis. By doing this type of analysis the authors provided insights into disease pathogenesis that would not otherwise have been apparent. For example, network analysis of ...
Inflammation is a hallmark of many diseases like diabetes, cancers, atherosclerosis and arthritis. Thus, lots of concerns have been raised toward developing novel anti-inflammatory agents. Many alternative herbal medicines possess excellent anti-inflammatory properties, yet their precise mechanisms of action are yet to be elucidated. Here, a novel systems pharmacology approach based on a large number of chemical, biological and pharmacological data was developed and exemplified by a probe herb Folium Eriobotryae, a widely used clinical anti-inflammatory botanic drug. The results show that 11 ingredients of this herb with favorable pharmacokinetic properties are predicted as active compounds for anti-inflammatory treatment. In addition, via systematic network analyses, their targets are identified to be 43 inflammation-associated proteins including especially COX2, ALOX5, PPARG, TNF and RELA that are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway, the rheumatoid
Autophagy plays an essential role in cell survival/death and functioning. Modulation of autophagy has been recognized as a promising therapeutic strategy against diseases/disorders associated with uncontrolled growth or accumulation of biomolecular aggregates, organelles or cells including those caused by cancer, aging, neurodegeneration, and liver diseases such as α1-antitrypsin deficiency. Numerous pharmacological agents that enhance or suppress autophagy have been discovered. However, their molecular mechanisms of action are far from clear. Here we collected a set of 225 autophagy modulators and carried out a comprehensive quantitative systems pharmacology (QSP) analysis of their targets using both existing databases and predictions made by our machine learning algorithm. Autophagy modulators include several highly promiscuous drugs (e.g. artenimol and olanzapine acting as activator, fostamatinib as inhibitor, or melatonin as dual-modulator), as well as selected drugs uniquely targeting specific
Blood pressure (BP) is a complex trait that is influenced by both genetic and environment factors. Recent genome-wide association studies (GWAS) have identified about 30 genetic loci that are associated with systolic and diastolic blood pressure (SBP, DBP) and hypertension. However, the molecular mechanisms underlying the GWAS associations remain unclear. We hypothesize that BP-associated genetic variants with both strong and subtle effects drive shifts in gene subnetworks that in turn affect BP. We surveyed BP-associated molecular interactions in Framingham offspring cohort participants (n=2461; 55% women; age range 40-92 yrs.) by integrating gene expression profiles, expression-associated SNPs (eSNPs), and BP GWAS with network approaches. Peripheral whole blood samples were collected and large-scale transcriptomic microarray analysis was performed on all available participants who attended a clinic visit in 2005-2008. Based on pedigrees the samples were split into a discovery set (n=1421) and ...
Alzheimers disease (AD) is the most common cause of dementia worldwide. One of the main pathological changes that occurs in AD is the intracellular accumulation of hyperphosphorylated Tau protein in neurons. Cyclin-dependent kinase 5 (CDK5) is one of the major kinases involved in Tau phosphorylation, directly phosphorylating various residues and simultaneously regulating various substrates such as kinases and phosphatases that influence Tau phosphorylation in a synergistic and antagonistic way. It remains unknown how the interaction between CDK5 and its substrates promotes Tau phosphorylation, and systemic approaches are needed that allow an analysis of all the proteins involved. In this review, the role of the CDK5 signaling pathway in Tau hyperphosphorylation is described, an in silico model of the CDK5 signaling pathway is presented. The relationship among these theoretical and computational models shows that the regulation of Tau phosphorylation by PP2A and glycogen synthase kinase 3β (GSK3β) is
ChEBI and genome-scale metabolic reconstructions Neil Swainston Manchester Centre for Integrative Systems Biology 2 nd ChEBI User Group Workshop, EMBL-EBI, Hi…
This ${affineX}. Is licensed under a Creative Commons ${SC-} License. In addition to the (SLA) licenses including the enhanced (UBMTA) and the release that forms the ease that dosent while mininizing the cost s of publication of this document were not defrayed in part or in whole by the payment of page charges. The document must therefore be hereby marked non-advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact unless otherwise indicated by authors with competing interest statments found herein. Content for informational and educational use only. All rights reserved. The contents provided here are solely the responsibility of the author and dose not identify or necessarily represent the official views, components of/or by a Science Education Partnership, Awards, or the NIH Research Resources/ Human Health Services. The Administration has offered regulations from the Department of Health and Human Services (Standards for Privacy of Individually Identifiable ...
Applications on Synthetic Biology, Synthetic Biology conservation, Genomics Products, Synthetic Biology products, Metabolomics, Computational Systems Biology Conference, Structural Biology, Chemical Biology, Stem Cell Biology
This subject deals primarily with equilibrium properties of macroscopic and microscopic systems, basic thermodynamics, chemical equilibrium of reactions in gas and solution phase, and macromolecular interactions.
This trial is investigating the pharmacodynamics of raltegravir with emtricitabine/tenofovir disoproxil fumarate in patients with chronic HIV 1 infections
Thorough and accessible, this book presents the design principles of biological systems, and highlights the recurring circuit elements that make up biological networks. It provides a simple mathematical framework which can be used to understand and even design biological circuits. The textavoids specialist terms, focusing instead on several well-studied biological systems that concisely demonstrate key principles. An Introduction to Systems Biology: Design Principles of Biological Circuits builds a solid foundation for the intuitive understanding of general principles. It encourages the reader to ask why a system is designed in a particular way and then proceeds to answer with simplified models.
In a cell with no KRAS mutations, a known tumor suppressor called neurofibromin keeps healthy KRAS proteins well-behaved. But most KRAS mutations are overly active and cannot be controlled by neurofibromin. When mutated KRAS is present, neurofibromin attempts to control the mutant KRAS at the expense of controlling the healthy KRAS. So why is the KRAS G13D mutation any different? Why does it respond to Cetuximab? The scientists discovered that even though KRAS G13D is overly active, it is doing so without neurofibromin being aware. Thus, neurofibromin can still keep the healthy KRAS under control. Additionally, the researchers demonstrated that cetuximab will only work to suppress tumors as long as there is neurofibromin available to suppress the activity of healthy KRAS. This work demonstrates the power of computational systems biology approaches to address problems in personalized medicine, says Stites. Doctors could sequence the gene to find out if the patient has this KRAS G13D variant, ...
The study of life, biology, has been transformed in recent decades by powerful new ways of asking fundamental questions about how living organisms work. In particular, molecular approaches are revealing both the incredible complexity of organization at the cellular level, and the underlying principles drawn from chemistry, physics and information science that will eventually enable us to understand that complexity.. The Department of Cell and Systems Biology brings together biologists who study life at the level of molecules to functioning individual organisms. Our undergraduate programs reflect this diversity and research strength. Since cells are the basic units of life, it is important to understand how molecular mechanisms control cells and how cells organize the developmental and physiological processes of whole organisms. These relationships encompass molecular biology, cell biology, developmental biology, genetics and physiology. These relationships are also complex, requiring studies of ...
The aim of this course is that the students learn how to combine graph theory and probability theory to infer graphical models from real-world data. In the course we will focus on Bayesian networks, which can for example be used to infer gene regulatory networks and protein pathways in systems biology research. After a very brief introduction to typical biological applications, we will consider Bayesian networks from a statistical perspective. As Bayesian networks bring together graph theory and probability theory, we will first discuss various graph theoretical concepts, before we can start modelling graphs statistically ...
Genomics-based drug discovery utilizing sequencing data for elucidation of candidate targets has led to the development of a number of successful treatments in the last decades. However, the molecular driver signals for many complex diseases cannot be easily derived from genome sequencing. Functional profiling studies, such as those involving the detection of protein interaction networks or the effects of perturbations with small molecules or siRNAs on cellular phenotypes, offer a complementary approach for the identification of molecular vulnerabilities that can be exploited in the development of new treatment strategies. The goal of this thesis was to develop computational systems biology methods for supporting such functional endeavors, and through their application use cases, to elucidate novel disease driver signals in cancer and Alzheimers disease networks. The availability of functional profiling data (such as biochemical target selectivity information or efficacy readouts) for numerous ...
Titolo ricerca:Image based surface matching oriented to macromolecular functionalannotation and interaction screening Short CV: Ivan Merelli received the Master of Science in Biomedical Engineering from the Politecnico di Milano, with a thesis about molecular surface modelling and analysis. In February 2009 he received a PhD in Computer Science from the Università di Milano Bicocca with a research about surface matching for macromolecular docking. His research activities concern the development of software for sequence based genomics and for structural proteomics researches, with particular interest in protein-protein interactions. He works actively on the implementation of high performance bioinformatics software using cluster infrastructures and grid distributed platforms. He has been involved in the development of databases and computational solutions for projects of Integrative System Biology, gene expression analyses and drug discovery. Nowadays he is researcher at Institute of Biomedical ...