Priyanshu Singh Raikwar

Research Interests

My pronouns are he/him

My work concerns antimicrobial-resistant (AMR) pathogens, which are a major threat to human and animal health. The decline in the efficacy of antimicrobials has led to major investment in identifying new compounds that can disrupt or destroy bacterial cells. Cell walls, surface proteins, and efflux pumps are all potential targets but questions remain about optimal foci for directed pathogen killing. On a theoretical level, one would want the target to be ubiquitous in bacteria, different from eukaryote hosts to avoid cross-reactivity, and fundamental to cell replication. From this perspective, there is no better target than the engine of protein synthesis, the bacterial ribosome. Ribosomal protein subunits (rps genes) are an important target for existing antimicrobials, including aminoglycosides, tetracyclines, macrolides, and chloramphenicol. However, the selection of novel ribosomal protein targets is rarely systematic and does not take into account the variation in the rps genes between bacterial strains and species.

For my DPhil, I combine extensive knowledge of bacterial (mainly E. coli) ribosome structure with the domain-wide archives of genetic variation among the 53 rps genes. This will allow in silico predictions of protein interactions with multiple drug classes, and their sensitivity and specificity. Using bioinformatics and structural biology, I aim to understand the structure-activity relationship between drugs and ribosomal protein subunits in natural bacterial populations. This requires careful characterization of phylogenetic relationships, selection acting on rps genes, and the role of de novo mutation and horizontal gene transfer in the spread of AMR between strains and species. Wet lab and dry lab approaches will help me investigate the structural and evolutionary effects of antibiotics on these proteins providing a strong and systematic foundation for discovering novel therapeutic targets and compounds to combat AMR.

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