Identification of Bacterial Post-translational Modifications that Regulate Antimicrobial Resistance
Lead Research Organisation:
Cardiff University
Department Name: Chemistry
Abstract
This PhD project aims to identify protein post-translational modifications that regulate antimicrobial resistance of bacteria.
Drug-resistant bacteria kill over 700,000 people a year worldwide and have become serious threats to global healthcare systems. If we leave the problem of antimicrobial resistance unattended, the annual death toll could rise to 10 million by 2050. Thus, there is a clear need to understand the regulatory mechanisms of antimicrobial resistance as it will facilitate development of new therapeutics against bacterial infection.
Post-translational modifications can confer novel properties to the modified proteins, including changes in protein activity, subcellular localisation, interaction partners, and stability. Recent advances in proteomics have revealed that a wide range of bacterial proteins, including those relevant to drug resistance, are subjected to different post-translational modifications. However, the functional significance of these identified post-translational modifications remains largely unknown. To address this problem, we will apply techniques in different disciplines, including:
Analytical science (to identify post-translational modifications uniquely present in drug-resistant bacteria).
Synthetic biology (using genetic code expansion to incorporate amino acids with post-translational modifications).
Chemical biology (to characterise the functions of specific post-translational modification in biochemical assays and bacterial cells).
Our studies will likely reveal new therapeutic targets against bacterial infections, setting the corner stone for subsequent drug discovery research.
Drug-resistant bacteria kill over 700,000 people a year worldwide and have become serious threats to global healthcare systems. If we leave the problem of antimicrobial resistance unattended, the annual death toll could rise to 10 million by 2050. Thus, there is a clear need to understand the regulatory mechanisms of antimicrobial resistance as it will facilitate development of new therapeutics against bacterial infection.
Post-translational modifications can confer novel properties to the modified proteins, including changes in protein activity, subcellular localisation, interaction partners, and stability. Recent advances in proteomics have revealed that a wide range of bacterial proteins, including those relevant to drug resistance, are subjected to different post-translational modifications. However, the functional significance of these identified post-translational modifications remains largely unknown. To address this problem, we will apply techniques in different disciplines, including:
Analytical science (to identify post-translational modifications uniquely present in drug-resistant bacteria).
Synthetic biology (using genetic code expansion to incorporate amino acids with post-translational modifications).
Chemical biology (to characterise the functions of specific post-translational modification in biochemical assays and bacterial cells).
Our studies will likely reveal new therapeutic targets against bacterial infections, setting the corner stone for subsequent drug discovery research.