Structural and Functional Analysis of the Host Parasite Interaction Network Using Plasmodium as Case Study
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Structural and Functional Analysis of the Host Parasite Interaction Network Using Plasmodium as Case Study
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| Creator |
Bhattacharyya, Madhumita
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| Subject |
Structural Biology & Bioinformatics
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| Description |
Parasitic diseases caused by protozoan pathogens results into millions of deaths per year in addition to substantial suffering and socioeconomic decline worldwide. Active research for understanding host–parasite infection biology in order to develop improved therapeutics is of prime importance due to lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host–parasite interactions.
A top-down system analysis protocol has been developed to construct and analyze large scale protein-protein interaction network using various graph theoretical approaches to identify highly interacting hub and central proteins. Further, an in-silico knock-out (KO) approach is implemented to isolate important interacting proteins (IIPs), which in principle can elicit significant impact on the integrity of the interaction networks. This network biology protocol is applied on Plasmodium falciparum interactome to identify a small set of proteins as important interacting proteins (IIPs), which not only play crucial role in intra-pathogen network integrity, stage specificity but also interact with various human proteins involved in multiple metabolic pathways within the host cell. These IIPs could be used as potential drug targets in malarial research. Stage specific metabolic network was also constructed for P. falciparum followed by its analysis at intra-pathogen and host-pathogen condition.
Similar network analysis approach was used to study an interaction network of deregulated set of gene in mutant P53 condition in order to identify important hub proteins. Analysis of important interactions at the molecular level is also crucial. In a case study, an E3 ubiquitin ligase (COP1) mediated regulation of adipocyte triglyceride lipase (ATGL) protein was studied using molecular modeling and docking techniques. In another case study Inhibition of DNA topoisomerase by SQDG was studied. Origin and evolution of DNA-(C5)-methyltransferase was studied across the tree of life. This large scale phylogenetic study elucidated gradual complexity in the DNMT and other methyltransferase genes.
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| Date |
2016-09
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| Type |
Thesis
NonPeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2560/1/Thesis%2DMadhumita.pdf
Bhattacharyya, Madhumita (2016) Structural and Functional Analysis of the Host Parasite Interaction Network Using Plasmodium as Case Study. PhD thesis, C U . |
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| Relation |
http://www.eprints.iicb.res.in/2560/
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