Dataset Information

Mandlik2013 - Synthetic circuit of IPC synthase in Leishmania

ABSTRACT: Mandlik2012 - Synthetic circuit of IPC synthase in Leishmania A genetic circuit for the targeted enzyme inositol phosphorylceramide (IPC) synthase belonging to the protozoan parasite Leishmania is constructed by Mandlik et al. (2013). This model is described in the article: Synthetic circuit of inositol phosphorylceramide synthase in Leishmania: a chemical biology approach Mandlik V., Limbachiya D., Shinde S., Mol M, S., Singh, S. J Chem Biol. January 2013 Abstract: Building circuits and studying their behavior in cells is a major goal of systems and synthetic biology. Synthetic biology enables the precise control of cellular states for systems studies, the discovery of novel parts, control strategies, and interactions for the design of robust synthetic systems. To the best of our knowledge, there are no literature reports for the synthetic circuit construction for protozoan parasites. This paper describes the construction of genetic circuit for the targeted enzyme inositol phosphorylceramide synthase belonging to the protozoan parasite Leishmania. To explore the dynamic nature of the circuit designed, simulation was done followed by circuit validation by qualitative and quantitative approaches. The genetic circuit designed for inositol phosphorylceramide synthase (Biomodels Database—MODEL1208030000) shows responsiveness, oscillatory and bistable behavior, together with intrinsic robustness. This model is hosted on BioModels Database and identified by: MODEL1208030000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

DISEASE(S): Leishmaniasis

SUBMITTER: Vijayalakshmi Chelliah

PROVIDER: MODEL1208030000 | BioModels | 2005-01-01

REPOSITORIES: BioModels

ACCESS DATA

Publications

Synthetic circuit of inositol phosphorylceramide synthase in Leishmania : a chemical biology approach.

Mandlik Vineetha V Limbachiya Dixita D Shinde Sonali S Mol Milsee M Singh Shailza S

Journal of chemical biology 20130103 2

Building circuits and studying their behavior in cells is a major goal of systems and synthetic biology. Synthetic biology enables the precise control of cellular states for systems studies, the discovery of novel parts, control strategies, and interactions for the design of robust synthetic systems. To the best of our knowledge, there are no literature reports for the synthetic circuit construction for protozoan parasites. This paper describes the construction of genetic circuit for the targete ...[more]

PMID: 24386012

Similar Datasets

Project description:Gardner2000 - genetic toggle switch in E.coli The behaviour of the genetic toggle switch and the conditions for bistability has been studies using a synthetic, bistable gene circuit. This model is described in the article: Construction of a genetic toggle switch in Escherichia coli. Gardner TS, Cantor CR, Collins JJ Nature. 2000 Jan 20;403(6767):339-42. Abstract: It has been proposed' that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage lambda switch and the Cyanobacteria circadian oscillator. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch-a synthetic, bistable gene-regulatory network-in Escherichia coli and provide a simple theory that predicts the conditions necessary for bistability. The toggle is constructed from any two repressible promoters arranged in a mutually inhibitory network. It is flipped between stable states using transient chemical or thermal induction and exhibits a nearly ideal switching threshold. As a practical device, the toggle switch forms a synthetic, addressable cellular memory unit and has implications for biotechnology, biocomputing and gene therapy. This model is hosted on BioModels Database and identified by: BIOMD0000000507 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Boada2016 - Incoherent type 1 feed-forward loop (I1-FFL) A synthetic-biology mathematical modelling framework that was constructed to provide guidelines for experimental implementation and parameter optimisation resulted in a biological device demonstrating desired behaviour. This model is described in the article: Multi-objective optimization framework to obtain model-based guidelines for tuning biological synthetic devices: an adaptive network case. Boada Y, Reynoso-Meza G, Picó J, Vignoni A. BMC Syst Biol 2016 Mar; 10: 27 Abstract: Model based design plays a fundamental role in synthetic biology. Exploiting modularity, i.e. using biological parts and interconnecting them to build new and more complex biological circuits is one of the key issues. In this context, mathematical models have been used to generate predictions of the behavior of the designed device. Designers not only want the ability to predict the circuit behavior once all its components have been determined, but also to help on the design and selection of its biological parts, i.e. to provide guidelines for the experimental implementation. This is tantamount to obtaining proper values of the model parameters, for the circuit behavior results from the interplay between model structure and parameters tuning. However, determining crisp values for parameters of the involved parts is not a realistic approach. Uncertainty is ubiquitous to biology, and the characterization of biological parts is not exempt from it. Moreover, the desired dynamical behavior for the designed circuit usually results from a trade-off among several goals to be optimized.We propose the use of a multi-objective optimization tuning framework to get a model-based set of guidelines for the selection of the kinetic parameters required to build a biological device with desired behavior. The design criteria are encoded in the formulation of the objectives and optimization problem itself. As a result, on the one hand the designer obtains qualitative regions/intervals of values of the circuit parameters giving rise to the predefined circuit behavior; on the other hand, he obtains useful information for its guidance in the implementation process. These parameters are chosen so that they can effectively be tuned at the wet-lab, i.e. they are effective biological tuning knobs. To show the proposed approach, the methodology is applied to the design of a well known biological circuit: a genetic incoherent feed-forward circuit showing adaptive behavior.The proposed multi-objective optimization design framework is able to provide effective guidelines to tune biological parameters so as to achieve a desired circuit behavior. Moreover, it is easy to analyze the impact of the context on the synthetic device to be designed. That is, one can analyze how the presence of a downstream load influences the performance of the designed circuit, and take it into account. This model is hosted on BioModels Database and identified by: BIOMD0000000696. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:Obesity is becoming increasingly widespread in developed countries, and is often associated with heart diseases and diabetes. Elevated levels of plasma free fatty acids are a biochemical hallmark of obesity. Unlike plants and bacteria, mammals cannot utilize fatty acids to generate glucose because of the lack of glyoxylate shunt enzymes. Instead, fatty acids are used for energy storage, and their utilization is regulated at multiple levels ranging from hormonal to metabolic ensuring that glucose is preferentially oxidized before fatty acids. Here we designed a synthetic gene-metabolic circuit to alter the intracellular signaling and metabolic pathways that control fatty acid metabolism. By introducing the Escherichia coli glyoxylate shunt enzymes, isocitrate lyase (AceA) and malate synthase (AceB), into the mitochondria of human hepatocytes, we demonstrated that fatty acid utilization is preferentially increased while glucose uptake is significantly reduced. This bacterial pathway diverts signal metabolites (citrate, acetyl-CoA, and malonyl-CoA) that inhibits fatty acid uptake and provides an additional channel for fatty acid utilization. Remarkably, the hepatocytes readily adapted to the synthetic circuit by a series of global transcriptional and post-translational changes in metabolic and signal transduction pathways that further advanced our design objective. This systems approach illustrates the logic of the synergistic interaction between metabolism and signal transduction. The ready acceptance of this non-native pathway by hepatocytes suggests the plasticity of liver metabolism and opens a possibility for the synthetic approach in regulating human metabolism. Experiment Overall Design: Wild type (WT) human hepatocyte HepG2 and HepG2 cells stably transfected with pBudaceAB (designated ACE), a vector containing isocitrate lyase and malate synthase from E. coli, were analyzed after 24hour exposure to palmitate. Cells were seeded at 70% confluency in 10cm plates with DMEM growth media augmented with 300uM palmitate. After 24hours, total RNA was harvested and hybrized to Affymetrix HG_U133A 2.0 GeneChips. Data was processed using GCOS 1.2 software. Experiment Overall Design: 2 WT biological replicates and 2 ACE biological replicates were analyzed. Experiment Overall Design:

Dataset Information

Mandlik2013 - Synthetic circuit of IPC synthase in Leishmania

Publications

Synthetic circuit of inositol phosphorylceramide synthase in Leishmania : a chemical biology approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure