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Ullrich, A.

Publications and source records attributed to Ullrich, A..

2 recordsLinked to original sources

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

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