| 21 |
IPD5439 |
An integrated proteo-transcriptomics approach reveals novel drug targets against multidrug resistant Escherichia coli |
Manish Kumar |
Infections due to multidrug-resistant (MDR) Escherichia coli are associated with severe morbidity and mortality, worldwide. Microbial drug resistance is a complex phenomenon which is conditioned by an interplay of several genomic, transcriptomic and proteomic factors. Here, we have conducted an integrated transcriptomics and proteomics analysis of MDR E. coli to...
Infections due to multidrug-resistant (MDR) Escherichia coli are associated with severe morbidity and mortality, worldwide. Microbial drug resistance is a complex phenomenon which is conditioned by an interplay of several genomic, transcriptomic and proteomic factors. Here, we have conducted an integrated transcriptomics and proteomics analysis of MDR E. coli to identify genes which are differentially expressed at both mRNA and protein levels. Using RNA-Seq and SWATH-LC MS/MS it was discerned that 763 genes/proteins exhibited differential expression. Of these, 52 genes showed concordance in differential expression at both mRNA and protein levels with 41 genes exhibiting overexpression and 11 genes exhibiting under expression. Bioinformatic analysis using GO-terms, COG and KEGG functional annotations revealed that the concordantly overexpressed genes of MDR E. coli were involved primarily in biosynthesis of secondary metabolites, aminoacyl-tRNAs and ribosomes. Protein–protein interaction (PPI) network analysis of the concordantly overexpressed genes revealed 81 PPI networks and 10 hub proteins. The hub proteins (rpsI, aspS, valS, lysS, accC, topA, rpmG, rpsR, lysU, and spmB) were found to be involved in aminoacylation of tRNA and lysyl-tRNA and, translation. Further, it was discerned that three hub proteins - smpB, rpsR, and topA were non homologous to human proteins and were involved in several biological pathways directly and/or indirectly related to antibiotic stress. Also, absence of homology ensures a little cross-reactivity of their inhibitors/drugs with human proteins and undesirable side effects. Thus, these proteins might be explored as novel drug targets against both drug-resistant and -sensitive populations of E. coli.
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University of Delhi, New Delhi, Delhi, India |
Bottom-up |
2025-03-12 |
11893563
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| 22 |
IPD2711 |
Hiss of death - Biogeographical venom variation in the Indian spectacled cobra (Naja naja) underscores the pressing need for pan-India efficacious snakebite therapy |
Dr. Kartik Sunagar |
The project aims at investigating the snake venom variability of Naja naja populations from six different biogeographic zones across India
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Evolutionary Venomics Lab, Center for Ecological Sciences, Indian Institute of Science, Bangalore, India |
Shotgun proteomics |
2025-03-29 |
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| 23 |
IPD9759 |
From birth to bite: the evolutionary ecology of India's medically most important snake venoms |
Dr. Kartik Sunagar |
Venoms of N. naja and D. russelii individuals of various developmental stages, including neonates (<30 days), juveniles (between 1 to 12 months), and mature individuals (>36 months), were sampled with permission from the state forest department of Karnataka. 226 individuals and 9 clutches were examined, including periodic venom collection (every...
Venoms of N. naja and D. russelii individuals of various developmental stages, including neonates (<30 days), juveniles (between 1 to 12 months), and mature individuals (>36 months), were sampled with permission from the state forest department of Karnataka. 226 individuals and 9 clutches were examined, including periodic venom collection (every three months) from the same N. naja and D. russelii juvenile individuals to track ontogenetic changes across time. Freshly collected venoms were flash-frozen in liquid nitrogen, lyophilised and stored at -80° C. Venoms were fractionated using RP-HPLC and SDS-PAGE and subjected to tandem mass spectrometry for toxin identification. The relative abundance of each toxin family were estimated and compared across different developmental stages.
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Evolutionary Venomics Lab, Center for Ecological Sciences, Indian Institute of Science, Bangalore, India |
Bottom-up |
2025-03-29 |
39075553
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| 24 |
IPD6520 |
Elusive elapid: Biogeographic venom variation in Indian kraits and its repercussion on snakebite therapy |
Dr. Kartik Sunagar |
Snakebite is a major public health concern in many parts of the world, including India, where over 58,000 deaths occur annually due to this highly neglected tropical disease. The common krait (Bungarus caeruleus), one of the ‘big four’ Indian snakes, is responsible for the second-highest number of snakebite-related deaths in...
Snakebite is a major public health concern in many parts of the world, including India, where over 58,000 deaths occur annually due to this highly neglected tropical disease. The common krait (Bungarus caeruleus), one of the ‘big four’ Indian snakes, is responsible for the second-highest number of snakebite-related deaths in the country. The venom protein composition of common krait venoms from different locations were investigated. Venoms were pre-fractionated using RP-HPLC and SDS-PAGE, and subjected to mass spectromentry analysis. The relative abundance of each toxin family was estimated and compared across different locations.
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Evolutionary Venomics Lab, Center for Ecological Sciences, Indian Institute of Science, Bangalore, India |
Bottom-up |
2025-03-29 |
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| 25 |
IPD6038 |
Candida glabrata GPI-anchored cell surface associated aspartyl protease CgYps1 and CgYps7 interactome analysis in the total cell extracts of A-498 human renal epithelial cell line |
Dr Rupinder Kaur |
The project is aimed at identifying host epithelial proteins that interact with two different cell-surface associated aspartyl proteases (CgYps1 and CgYps7) in Candida glabrata cells.
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Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics (CDFD) |
Gel-based experiment, Affinity purification coupled with mass spectrometry proteomics |
2025-04-16 |
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| 26 |
IPD3790 |
SWATH-LC MS-based quantitative secretomics reveals trigger factor as a novel drug |
Manish Kumar |
In the present study, we have analysed the secretory proteins of multidrug resistant
(MDR) and -sensitive strains of E. coli isolated from a prominent urban river (Yamuna)
which traverses through the National Capital Region of India. Both the strains
investigated in this study were phylogroup D strains and of the same genomic clade...
In the present study, we have analysed the secretory proteins of multidrug resistant
(MDR) and -sensitive strains of E. coli isolated from a prominent urban river (Yamuna)
which traverses through the National Capital Region of India. Both the strains
investigated in this study were phylogroup D strains and of the same genomic clade as
revealed by REP-, ERIC- and BOX-PCR based genotypic fingerprinting.
Comparative secretomic analysis of multidrug-resistant and -sensitive strains was performed
and the biological functions and metabolic pathways of the differentially expressed
secreted proteins were elucidated. Subsequently, Protein-protein interaction (PPI) networks of the differentially expressed secretory proteins were determined followed by identification of hub proteins. The similarity of the hub proteins with the human proteins was determined and those exhibiting non-homology with human proteins were explored as potential drug targets against MDR E. coli.
Our results revealed 675 differentially expressed proteins of which 54 proteins were overexpressed and 235 proteins were underexpressed . The differentially expressed secreted proteins were primarily involved in metabolic pathways, biosynthesis of amino acids/proteins and secondary metabolites and stress response. The PPI networks of the overexpressed proteins revealed a hub protein — trigger factor (tig) which was non-homologous to the human proteins. Tig is a cold stress molecular chaperones protein which regulates several biological pathways directly/indirectly related to antibiotic stress.
To combat antimicrobial resistance, new drugs which bind to novel biological
pathways/components of the pathogens are urgently needed. Microbial secreted proteins
(secretome) are important for pathogenesis and adaptation/survival in various environmental
stresses, including antibiotics. Thus, they can be explored as novel drug targets. Thus, the protein identified in our study can be explored as a novel drug target against E. coli, inhibitors of which might not cross-react with human proteins.To the best of our knowledge, this is the first study comparing the secretomes of MDR and -sensitive strains of E. coli isolated from a waterbody.
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University of Delhi, New Delhi, Delhi, India |
Bottom-up |
2025-04-23 |
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| 27 |
IPD3843 |
Comparative proteomic analysis of secretomes from engineered Penicillium funiculosum modulated with sugarcane bagasse |
Dr Syed Shams Yazdani |
Sugarcane bagasse (SCB), one of the most abundant plant feedstocks is at the leading front of the biofuel industry based on the potential to promote economic, social and environmental development worldwide through sustainable set-ups related to energy production. This complex biomass requires a vast array of carbohydrate active enzymes (CAZymes)...
Sugarcane bagasse (SCB), one of the most abundant plant feedstocks is at the leading front of the biofuel industry based on the potential to promote economic, social and environmental development worldwide through sustainable set-ups related to energy production. This complex biomass requires a vast array of carbohydrate active enzymes (CAZymes) mostly from filamentous fungi for its deconstruction to monomeric sugars for the production of value-added fuels and chemicals. In this study, we attempted to evaluate the comprehensive repertoire of proteins in the secretome of an engineered Penicillium funiculosum, (PfMig188) in response to SCB. For this, a systematic approach was utilized for the cultivation of the fungus towards production of tailored enzymes specific for saccharification of SCB. This was done through the modulation of the production media with different concentrations of pretreated SCB (0 – 45 g/L) and the array of secreted proteins were identified by enzyme activity assay and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 280 proteins were detected in the secretome of PfMig188 with 46% of them being CAZymes. Modulation of the cultivation media with SCB up till 15 g/L enhanced the secretion of some importanthemicellulasesand cell wall modifying enzymes such as β-xylosidase (GH5, GH43), β-1,3-galactosidase (GH43), endo-1,3(4)-beta-glucanase (GH16), cutinase (CE5) and hydrophobic surface binding protein (HsbA)that works in synergy with the cellulases in the secretome to improve SCB saccharification by 20%. Our findings provide more insight on the enzyme system of PfMig188 for degradation of complex biomass such as SCB and highlights the important role of adjusting the culture medium composition with SCB for secretion of enzymes specific for its saccharification.
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Group Leader, Microbial Engineering Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) New Delhi, India |
Top-down |
2025-05-11 |
34446097
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| 28 |
IPD2854 |
Intelligent versus Blind response”- Unveiling a Hypercellulolytic Fungus Strategy for Efficient Polymeric Carbon Deconstruction via Multiplexed Quantitative Proteomics |
Dr Syed Shams Yazdani |
Fungi are ubiquitous and are often confronted with the need to secure utilisable carbon from their external growth milieu through the use of extracellular proteins to scavenge for carbon from a vast array of complex polymeric carbon sources. This attribute is conserved across evolution in fungi. To understand how filamentous...
Fungi are ubiquitous and are often confronted with the need to secure utilisable carbon from their external growth milieu through the use of extracellular proteins to scavenge for carbon from a vast array of complex polymeric carbon sources. This attribute is conserved across evolution in fungi. To understand how filamentous fungi extracellular proteins are modulated in response to the presence polymeric carbons in the environment, we have typed the array of the main extracellular proteins involved and their dynamics using a known hypercellulolytic fungus – Penicillium funiculosum (NCIM 1228), through multiplexed quantitative proteomics
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Group Leader, Microbial Engineering Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) New Delhi, India |
Shotgun proteomics |
2025-05-11 |
29597011
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| 29 |
IPD1450 |
Total proteome analysis of engineered/adapted E.coli strains with glucose/xylose co-utilization ability |
Dr Syed Shams Yazdani |
This project was about developing a bacterial strain that could consume a mixture of glucose and xylose simultaneously with higher ethanol productivity. In this study, an ethanologenic strain (SSK42) was made deficient in Carbon Catabolite Repression (CCR) by deleting the ptsG gene encoding EIIBCGlc component of PTS transport system. This...
This project was about developing a bacterial strain that could consume a mixture of glucose and xylose simultaneously with higher ethanol productivity. In this study, an ethanologenic strain (SSK42) was made deficient in Carbon Catabolite Repression (CCR) by deleting the ptsG gene encoding EIIBCGlc component of PTS transport system. This strain (SCD00) was then evolved for several generations on xylose containing minimal media. A strain (SCD78) was finally obtained that, unlike its parent strain could consume glucose and xylose simultaneously. Then we performed proteomics analysis of evolved and un-evolved strain. The strain SSK42 was also considered for proteome analysis as a reference for analysis. The starting strain – SSK42, is the derivative of E.coli B.
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Group Leader, Microbial Engineering Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) New Delhi, India |
Shotgun proteomics |
2025-05-11 |
35933385
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| 30 |
IPD1913 |
Proteomics and metabolic burden analysis to understand the impact of recombinant protein production on host cells |
Dr Syed Shams Yazdani |
Recombinant protein production (RPP) using Escherichia coli as an expression host is highly efficient, however, it also in¬ leads to strong host cell metabolic burden. Energy and biomass precursors are withdrawn from the host’s metabolism as they are required for plasmid replication, heterologous gene expression and protein production. In this...
Recombinant protein production (RPP) using Escherichia coli as an expression host is highly efficient, however, it also in¬ leads to strong host cell metabolic burden. Energy and biomass precursors are withdrawn from the host’s metabolism as they are required for plasmid replication, heterologous gene expression and protein production. In this study, we aim to investigate the effect of early and growth phase induction point on RPP. We have analysed and compared the proteomics data for growth-and protein production-phase to understand the cellular dynamics and recombinant protein-dependent product formation in process with respect to the two different hosts (M15 and DH5âº) and medium (minimal and complex) cultures. Differential gene analysis shows that significant changes in carbohydrate metabolism, transport metabolism, nucleotide metabolism, amino acid metabolism and energy metabolism. Comprehension of the obtain results suggest that growth inhibition does not showing effect on recombinant protein and product yield but there is an changes in intracellular nucleobases, translation, transcription and cellular metabolism which leads to the degradation and instability during product formation. Overall, deeper knowledge of the cellular behaviour during recombinant protein production can be used to better exploit omics data with the goal of rational strain development.
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Group Leader, Microbial Engineering Group, International Centre for Genetic Engineering and Biotechnology (ICGEB) New Delhi, India |
Top-down |
2025-05-11 |
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