Most bacteria cannot be grown in the laboratory, which means that their genetic diversity is hidden to traditional culture-based studies. We combined a new DNA extraction method, long-read sequencing, bioinformatics and chemical synthesis to access the genetic diversity of uncultured soil bacteria and abiotically decode it to discover bioactive small molecules.

A new screen platform named DEFUSE (DEath FUSion Escape) enables high-throughput discovery of small molecule protein degraders. DEFUSE identified SKPer1, a molecule that works by inducing proximity between an oncogenic driver and an E3 ligase, opening new avenues for targeted protein degradation.

Antibody–drug conjugates (ADCs) are promising targeted cancer therapies but have a limited payload scope. Antibody–bottlebrush prodrug conjugates offer modular synthesis and high drug-to-antibody ratios, enabling the use of a broad range of payloads, including lower potency drugs, while performing favorably compared to traditional ADCs in preclinical models.

We developed a universal control system and multitarget optimization framework that enables dynamic and synchronized expression of multiple genes and facilitates the overproduction of specific secondary metabolites in Streptomyces species.