LifeArc
University of Glasgow

Advancing antibacterial drug discovery to fight antimicrobial resistance

Antimicrobial resistance (AMR) is a growing global health issue. It occurs when bacteria evolve to resist antibiotics, making common infections harder to treat and increasing the risk of disease spread and severe illness. If left unchecked, the WHO estimates that by 2050, AMR could lead to 10 million deaths per year – surpassing deaths by cancer.

A major concern is gram-negative bacteria, examples of which can cause severe bloodstream and urinary tract infections as well as pneumonia. These bacteria have a complex cell wall that makes them difficult to treat with traditional antibiotics.

A promising new approach which could help to bypass this resistance and combat AMR is targeted protein degradation (TPD), which can selectively eliminate proteins within bacteria which are key for their survival. TPD uses small molecules to bring the bacteria’s own degradation machinery into proximity with the target protein and remove these essential proteins. Unlike traditional antibiotics, TPD could broaden the pool of drug targets to a larger range of proteins and reduce the likelihood of resistance mutations, as bacteria would need major genetic changes to avoid this protein degradation.

In bacteria, proteases are a group of enzymes which break down proteins that are essential for these bacteria’s survival. By exploring the roles of these proteases, it could be possible to block vital bacterial functions or trigger cell death.

Natasha’s project aims to identify underexplored bacterial proteases in gram-negative bacteria and probe their possible roles in degrading bacterial proteins. This research could uncover new tools to advance antibacterial research and accelerate the discovery of new drugs to address the global threat of AMR.

Biography

Through her Biochemistry undergraduate degree at the University of Leeds, Natasha discovered her passion for early drug discovery, learning a wide variety of techniques across many disease areas. She undertook a placement year during her BSc at LifeArc, which enabled her to apply her scientific knowledge to real-world patients. Following her graduation with a First Class Honours, she joined LifeArc’s Chemical Biology team, where she has continued to develop her skills. In her role, she has carried out research in novel drug discovery aimed towards improving translational science for patients and she hopes to further scientific research in the field of AMR through this PhD at LifeArc and the University of Glasgow.