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Systems and Synthetic Biology

Mamta Singh, Anuradha Vaidya
Synthetic biology is a recent scientific approach towards engineering biological systems from both pre-existing and novel parts. The aim is to introduce computational aided design approach in biology leading to rapid delivery of useful applications. Though the term reprogramming has been frequently used in the synthetic biology community, currently the technological sophistication only allows for a probabilistic approach instead of a precise engineering approach. Recently, several human health applications have emerged that suggest increased usage of synthetic biology approach in developing novel drugs...
December 2015: Systems and Synthetic Biology
Javier Garcia-Bernardo, Margaret J Eppstein
Being able to design genetic regulatory networks (GRNs) to achieve a desired cellular function is one of the main goals of synthetic biology. However, determining minimal GRNs that produce desired time-series behaviors is non-trivial. In this paper, we propose a 'top-down' approach to evolving small GRNs and then use these to recursively boot-strap the identification of larger, more complex, modular GRNs. We start with relatively dense GRNs and then use differential evolution (DE) to evolve interaction coefficients...
December 2015: Systems and Synthetic Biology
Rupa Bhowmick, Abhishek Subramanian, Ram Rup Sarkar
Brain cancers demonstrate a complex metabolic behavior so as to adapt the external hypoxic environment and internal stress generated by reactive oxygen species. To survive in these stringent conditions, glioblastoma cells develop an antagonistic metabolic phenotype as compared to their predecessors, the astrocytes, thereby quenching the resources expected for nourishing the neurons. The complexity and cumulative effect of the large scale metabolic functioning of glioblastoma is mostly unexplored. In this study, we reconstruct a metabolic network comprising of pathways that are known to be deregulated in glioblastoma cells as compared to the astrocytes...
December 2015: Systems and Synthetic Biology
Johannes Starkbaum, Matthias Braun, Peter Dabrock
Synthetic biology is currently one of the most debated emerging biotechnologies. The societal assessment of this technology is primarily based on contributions by scientists and policy makers, who focus mainly on technical challenges and possible risks. While public dialogue is given, it is yet rather limited. This study explores public debates concerning synthetic biology based on a focus group study with citizens from Austria and Germany and contextualises the analysed public views with content from policy reports and previous empirical studies on public engagement...
December 2015: Systems and Synthetic Biology
Abderrahim Chafik
Breast cancer metastasis is a complex and still weakly understood process that involves diverse cellular pathways. It accounts for the majority of deaths from breast cancer. Recently, microRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, have been shown to be involved in breast cancer metastasis. In particular, in a recent work it has been found that miR-429 may have a role in the inhibition of migration and invasion of breast cancer cells. Its target gene CRKL has been identified as a potential candidate...
December 2015: Systems and Synthetic Biology
Vipin Thomas, Navya Raj, Deepthi Varughese, Naveen Kumar, Seema Sehrawat, Abhinav Grover, Shailja Singh, Pawan K Dhar, Achuthsankar S Nair
Expression of synthetic proteins from intergenic regions of E. coli and their functional association was recently demonstrated (Dhar et al. in J Biol Eng 3:2, 2009. doi:10.1186/1754-1611-3-2). This gave birth to the question: if one can make 'user-defined' genes from non-coding genome-how big is the artificially translatable genome? (Dinger et al. in PLoS Comput Biol 4, 2008; Frith et al. in RNA Biol 3(1):40-48, 2006a; Frith et al. in PLoS Genet 2(4):e52, 2006b). To answer this question, we performed a bioinformatics study of all reported E...
December 2015: Systems and Synthetic Biology
Chandramohan Bathula, Shailja Singh, Subhabrata Sen
[This corrects the article DOI: 10.1007/s11693-015-9171-0.].
December 2015: Systems and Synthetic Biology
Deepti Chachra, Pushpinder Kaur, Prasad Siddavatam, Prashanth Suravajhala, Hari Mohan Saxena
Brucellaphage Gadvasu (BpG) is a lytic phage infecting Brucella spp. Brucellaphages contain dsDNA as genetic material and are short-tailed particles with host-specificity. Here, we report the challenges on annotation in the complete genome sequence of BpG when compared with that of a recent broad host-range brucellaphage Pr, an original reference genome. The extracted DNA was subjected to genome sequencing with Illumina technology and assembled using SSAKE/Velvet. A significant number of genes were found to be similar between the phages with sequence analysis revealing conserved open reading frames that correspond to 33 gene ontology classifiers, transcriptional terminators and a few putative transcriptional promoters...
December 2015: Systems and Synthetic Biology
Chandramohan Bathula, Shailja Singh, Subhabrata Sen
Malaria a global pandemic has engulfed nearly 0.63 million people globally. It is high time that a cure for malaria is required to stop its ever increasing menace. Our commentary discusses the advent and contribution of diversity oriented synthesis (DOS) in the drug discovery efforts towards developing cure for malaria. DOS based on chemical genetics focusses on design and synthesis of molecular libraries which covers large tracts of biologically relevant chemical space. Herein we will discuss the applications, advantages, disadvantages and future directions of DOS with respect to malaria...
December 2015: Systems and Synthetic Biology
Chun-Liang Lin, Ting-Yu Kuo, Yang-Yi Chen
We introduce an idea of synthesizing a class of genetic registers based on the existing sequential biological circuits, which are composed of fundamental biological gates. In the renowned literature, biological gates and genetic oscillator have been unveiled and experimentally realized in recent years. These biological circuits have formed a basis for realizing a primitive biocomputer. In the traditional computer architecture, there is an intermediate load-store section, i.e. a register, which serves as a part of the digital processor...
December 2015: Systems and Synthetic Biology
Santanu Hati, Sudeepto Bhattacharya, Subhabrata Sen
Malaria a global pandemic has engulfed nearly 0.63 million people globally. It is high time that a cure for malaria is required to stop its ever increasing menace. Our commentary discusses the advent and contribution of genetic algorithm (GA) in the drug discovery efforts towards developing cure for malaria. GAs are computational models of Darwinian evolution, ideally capture and mimic the principles of genetic variation and natural selection to evolve good solutions through multiple iterations on the space of all possible candidate solutions, called the search space, to a given optimization problem...
December 2015: Systems and Synthetic Biology
Shalini Agarwal, Vijeta Sharma, Swastik Phulera, M Z Abdin, R Ayana, Shailja Singh
Carotenoids represent a diverse group of pigments derived from the common isoprenoid precursors and fulfill a variety of critical functions in plants and animals. Phytoene synthase (PSY), a transferase enzyme that catalyzes the first specific step in carotenoid biosynthesis plays a central role in the regulation of a number of essential functions mediated via carotenoids. PSYs have been deeply investigated in plants, bacteria and algae however in apicomplexans it is poorly studied. In an effort to characterize PSY in apicomplexans especially the malaria parasite Plasmodium falciparum (P...
December 2015: Systems and Synthetic Biology
Swati Garg, Shalini Agarwal, Surbhi Dabral, Naveen Kumar, Seema Sehrawat, Shailja Singh
Malaria, a leading parasitic killer, is caused by Plasmodium spp. The pathology of the disease starts when Plasmodium merozoites infect erythrocytes to form rings, that matures through a large trophozoite form and develop into schizonts containing multiple merozoites. The number of intra-erythrocytic merozoites is a key-determining factor for multiplication rate of the parasite. Counting of intraerythrocytic merozoites by classical 2-D microscopy method is error prone due to insufficient representation of merozoite in one optical plane of a schizont...
December 2015: Systems and Synthetic Biology
Swati Garg, Vijeta Sharma, Dandugudumula Ramu, Shailja Singh
Plasmodium falciparum perforin like proteins (PfPLPs) are an important arsenal for the entry and exit of malaria parasites. These proteins bind and oligomerize on the membrane in calcium dependent manner and form an open pore. The calcium dependent pore forming activity of PLPs is usually conferred by their C2 like C-terminal domain. Here, we have tried to elucidate the calcium binding residues in the C-terminal domain of PfPLP1, a member of P. falciparum PLPs, playing a crucial role in calcium dependent egress of blood stage parasites...
December 2015: Systems and Synthetic Biology
Sonal Gupta, Deepak Singh, Shailja Singh
Serpentine receptors with G-protein coupled receptor like seven transmembrane (7 TM) topology are identified in Plasmodium. A class of 7 TM receptors known as purinergic receptors binds to purines such as ADP, ATP and UTP and mediates important physiological functions including regulation of calcium signaling. Here we performed in silico analysis of Plasmodium falciparum serpentine receptors and found that one of the P. falciparum serpentine receptors, PfSR12 possess nucleotide binding consensus P-loop sequence in addition to seven transmembrane domains...
December 2015: Systems and Synthetic Biology
Vijai Singh, Darren Braddick
The genome engineering toolkit has expanded significantly in recent years, allowing us to study the functions of genes in cellular networks and assist in over-production of proteins, drugs, chemicals and biofuels. Multiplex automated genome engineering (MAGE) has been recently developed and gained more scientific interest towards strain engineering. MAGE is a simple, rapid and efficient tool for manipulating genes simultaneously in multiple loci, assigning genetic codes and integrating non-natural amino acids...
December 2015: Systems and Synthetic Biology
Sebastian M Castillo-Hair, Elizabeth R Villota, Alberto M Coronado
Oscillatory responses are ubiquitous in regulatory networks of living organisms, a fact that has led to extensive efforts to study and replicate the circuits involved. However, to date, design principles that underlie the robustness of natural oscillators are not completely known. Here we study a three-component enzymatic network model in order to determine the topological requirements for robust oscillation. First, by simulating every possible topological arrangement and varying their parameter values, we demonstrate that robust oscillators can be obtained by augmenting the number of both negative feedback loops and positive autoregulations while maintaining an appropriate balance of positive and negative interactions...
September 2015: Systems and Synthetic Biology
Ilaria Massaiu, Lorenzo Pasotti, Michela Casanova, Nicolò Politi, Susanna Zucca, Maria Gabriella Cusella De Angelis, Paolo Magni
Small RNAs (sRNAs) are genetic tools for the efficient and specific tuning of target genes expression in bacteria. Inspired by naturally occurring sRNAs, recent works proposed the use of artificial sRNAs in synthetic biology for predictable repression of the desired genes. Their potential was demonstrated in several application fields, such as metabolic engineering and bacterial physiology studies. Guidelines for the rational design of novel sRNAs have been recently proposed. According to these guidelines, in this work synthetic sRNAs were designed, constructed and quantitatively characterized in Escherichia coli...
September 2015: Systems and Synthetic Biology
P Chellapandi, J Ranjani
Clustered regularly interspaced short palindromic repeats (CRISPRs) are direct features of the prokaryotic genomes involved in resistance to their bacterial viruses and phages. Herein, we have identified CRISPR loci together with CRISPR-associated sequences (CAS) genes to reveal their immunity against genome invaders in the thermophilic archaea and bacteria. Genomic survey of this study implied that genomic distribution of CRISPR-CAS systems was varied from strain to strain, which was determined by the degree of invading mobiloms...
September 2015: Systems and Synthetic Biology
R V S Uday Bhaskar, Richa Karmakar, Deepti Deepika, Mahesh S Tirumkudulu, K V Venkatesh
Studies on chemotaxis of Escherichia coli have shown that modulation of tumble frequency causes a net drift up the gradient of attractants. Recently, it has been demonstrated that the bacteria is also capable of varying its runs speed in uniform concentration of attractant. In this study, we investigate the role of swimming speed on the chemotactic migration of bacteria. To this end, cells are exposed to gradients of a non-metabolizable analogue of glucose which are sensed via the Trg sensor. When exposed to a gradient, the cells modulate their tumble duration, which is accompanied with variation in swimming speed leading to drift velocities that are much higher than those achieved through the modulation of the tumble duration alone...
September 2015: Systems and Synthetic Biology
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