Biology subjects

Ulaganathan, V. K.

Publications and source records attributed to Ulaganathan, V. K..

3 recordsLinked to original sources

bioRxiv2017

TraPS-VarI: a python module for the identification of STAT3 modulating germline receptor variants

MotivationHuman individuals differ because of variations in the DNA sequences of all the 46 chromosomes. Information on genetic variations altering the membrane-proximal binding sites for signal transducer of transcription 3 (STAT3) is valuable for understanding the genetic basis of cancer prognosis and disease progression (Ulaganathan et al, 2015). In this regard, non-synonymous coding region mutations resulting in the alteration of protein sequence in the juxtamembrane region of the type I membrane proteins are biologically and clinically relevant. The knowledge of such rare cell line- and individual-specific germline receptor variants is crucial for the investigation of cell-line specific biological mechanisms and genotype-centric therapeutic approaches.\n\nResultsHere we present TraPS-VarI (Transmembrane Protein Sequence Variant Identifier), a python module to rapidly identify human germline receptor variants modulating STAT3 binding sites by using the genetic variation datasets in the variant call format 4.0. For the found protein variants the module also checks for the availability of associated therapeutic agents and ongoing clinical trial studies.\n\nAvailabilityThe Source code and binaries are freely available for download at https://gitlab.com/VJ-Ulaganathan/TraPS-VarI and the documentation can be found at http://traps-vari.readthedocs.io/.\n\nContactulaganat@biochem.mpg.de & ulaganat@icloud.com\n\nSupplementary informationSupplementary data enclosed with the manuscript file.

bioinformatics↗

bioRxiv2017

DNA-dependent protein synthesis exhibited by cancer shed particulates

Genetic heterogeneity in tumours is the bonafide hallmark applicable to all cancer types (Burrell et al, 2013). Furthermore, deregulated ribosome biogenesis and elevated protein biosynthesis have been consistently associated with multiple cancer types (Ruggero, 2012; Ruggero & Pandolfi, 2003). We observed that under cultivation conditions almost all cancer cell types actively shed significant amount of particulates as compared to non-malignant cell lines requiring frequent changing of cultivation media. We therefore asked if cancer cell shed particulates might still retain biological activity associated with protein biosynthesis. Here, we communicate our observations of DNA-dependent protein biosynthetic activity exhibited by the cell-free particulates shed by the cancer cell lines. Using pulsed isotope labelling approach we confirmed the cell-free protein translation activity exhibited by particulates shed by various cancer cell lines. Interestingly, the bioactivity was largely dependent on temperature, pH and on 3-DNA elements. Our results demonstrate that cancer shed particulates are biologically active and may potentially drive expression of tissue non-specific promoters in distant organs.

cancer biology↗

bioRxiv2017

Antibody-Mediated Depletion Of Protein Variant Expression In Living Cells (Protein Interference)

A significant development in the field of human biology is the revelation of millions of unannotated protein sequence variants emerging from the several human genotyping and genome sequencing initiatives. This presents unique opportunities as well as confounding challenges in our understanding of how molecular signalling outcomes vary among individuals in the general population. As a result the conventional one drug fits all lines of approach in the drug discovery process is becoming obsolete. However, an innovative genotype-specific approach targeting protein sequence variants instead of a reference protein target is currently lacking. In this short communication we report a remarkable observation of antibody-mediated knockdown of intracellular protein expression. This suggests allele-specific inhibition of protein-variant expression can be achieved by intracellular delivery of lipid conjugated linear epitope-specific monoclonal antibodies. The results presented here demonstrate novel opportunities for interrogating the protein coding variations in the human genomes and new therapeutic strategies for the inhibition of pathogenic protein variants in a genotype-centric manner.

genomics↗