Targeted Bacterial Protein Degradation

Antibiotics are a vital pillar of modern medicine, and the rising impact of antimicrobial resistance drives the societal need for novel antibacterials. However, this is a difficult challenge as antibiotic hits for development are hard to find using traditional methods. Furthermore, a broken economic model does not incentivize pharma to work in the area.

This creates a greater burden on academia and public-private partnerships to fill the antibiotic pipeline with new antibiotics for development towards the clinic. Small molecules drugs typically interact with a target active site to inhibit a biological process. We will take an alternative approach; Targeted Bacterial Protein Degradation (TBPD).

Here, chemical degraders will be developed that seek out a desired bacterial protein target, and trigger its degradation by the bacterial proteasome. Instead of reversibly inhibiting a proteins biological function, we will destroy the protein permanently. This approach has not yet been demonstrated in an antibacterial context.

The project is highly multidisciplinary and involves a range of expertise across synthetic chemistry, biochemistry, microbiology and structural biology.

Our goal is to development new antibiotic strategies to contribute towards the global effort required to overcome antimicrobial resistance.