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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
Christian E Cuba, Alexander R Valle, Giancarlo Ayala-Charca, Elizabeth R Villota, Alberto M Coronado
Biomolecular networks that present oscillatory behavior are ubiquitous in nature. While some design principles for robust oscillations have been identified, it is not well understood how these oscillations are affected when the kinetic parameters are constantly changing or are not precisely known, as often occurs in cellular environments. Many models of diverse complexity level, for systems such as circadian rhythms, cell cycle or the p53 network, have been proposed. Here we assess the influence of hundreds of different parameter sets on the sensitivities of two configurations of a well-known oscillatory system, the p53 core network...
September 2015: Systems and Synthetic Biology
Srikanth Chiliveru, Mahesh Appari, Prashanth Suravajhala
Brucellosis is a zoonotic infection transmitted to humans from infected animals and is one of the widely spread zoonoses. Recently, six species were recognized within the genus Brucella wherein B. melitensis, B. suis and B. abortus are considered virulent for humans. While these species differ phenotypically by their pattern of metabolic activities, there has been an imperative need to understand pathogenesis of Brucella species. It has been foreseen that creating a human vaccine for Brucellosis would entail decreased dose of antibiotics...
June 2015: Systems and Synthetic Biology
Navya Raj, Agnes Helen, N Manoj, G Harish, Vipin Thomas, Shailja Singh, Seema Sehrawat, Shaguna Seth, Achuthsankar S Nair, Abhinav Grover, Pawan K Dhar
Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drug-target specific peptides. Recently, we experimentally demonstrated the artificial synthesis of novel proteins from non-coding regions of Escherichia coli genome. In this study, a library of synthetic peptides (Synpeps) was constructed from 2500 intergenic E...
June 2015: Systems and Synthetic Biology
Prerna Jain, Nitin Thukral, Lokesh Kumar Gahlot, Yasha Hasija
Interactions between proteins largely govern cellular processes and this has led to numerous efforts culminating in enormous information related to the proteins, their interactions and the function which is determined by their interactions. The main concern of the present study is to present interface analysis of cardiovascular-disorder (CVD) related proteins to shed lights on details of interactions and to emphasize the importance of using structures in network studies. This study combines the network-centred approach with three dimensional studies to comprehend the fundamentals of biology...
June 2015: Systems and Synthetic Biology
Aman Chandra Kaushik, Shakti Sahi
Systems biology addresses challenges in the analysis of genomics data, especially for complex genes and protein interactions using Meta data approach on various signaling pathways. In this paper, we report systems biology and biological circuits approach to construct pathway and identify early gene and protein interactions for predicting GPR142 responses in Type 2 diabetes. The information regarding genes, proteins and other molecules involved in Type 2 diabetes were retrieved from literature and kinetic simulation of GPR142 was carried out in order to determine the dynamic interactions...
June 2015: Systems and Synthetic Biology
Divya Wahi, Salma Jamal, Sukriti Goyal, Aditi Singh, Ritu Jain, Preeti Rana, Abhinav Grover
Cancer cells have upregulated DNA repair mechanisms, enabling them survive DNA damage induced during repeated rapid cell divisions and targeted chemotherapeutic treatments. Cancer cell proliferation and survival targeting via inhibition of DNA repair pathways is currently a very promiscuous anti-tumor approach. The deubiquitinating enzyme, USP1 is known to promote DNA repair via complexing with UAF1. The USP1/UAF1 complex is responsible for regulating DNA break repair pathways such as trans-lesion synthesis pathway, Fanconi anemia pathway and homologous recombination...
June 2015: Systems and Synthetic Biology
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