IBL Spotlight - Ben Wielstra and Chaoxian Bai
- Date
- Wednesday 15 January 2025
- Time
- Location
- Sylvius Building
- Room
- Room 1.4.31
Ben Wielstra
Unravelling an evolutionary mystery: the balanced lethal system in Triturus newts
A balanced lethal system is a deadly hereditary disease that causes the loss of fifty percent of offspring every generation. The most infamous example concerns the chromosome 1 syndrome affecting the salamander genus Triturus: the crested and marbled newts. All adults possess two forms of chromosome 1, known as 1A and 1B. Yet, according to the rules of Mendelian inheritance, 50% of offspring are homozygous, possessing either 1A or 1B twice (and lacking the other version). Such individuals die roughly halfway through embryological development – 50% of Triturus eggs never hatch! We show that Triturus’ 1A and 1B (1) are mostly conserved across the genus; (2) form two distinct, consecutive blocks in the genomes of both Lissotriton and Pleurodeles newts; and (3) share a phylogenetic relationship that is distinct from that of the rest of the Triturus genome.
Chaoxian Bai
Deciphering the Regulation and Antibiotic Production in Streptomyces through Synthetic Biology Approaches
Streptomyces, a soil-dwelling bacterium, plays a pivotal role in nature as a producer of bioactive compounds. Often referred to as "nature's medicine makers," these microorganisms synthesize specialized chemicals to protect themselves, many of which have been harnessed by humans to combat infections, cancer, and other diseases. Streptomyces coelicolor, a model streptomycete for antibiotic production, possesses a complex regulatory network that controls its secondary metabolism and morphological development. Deciphering this network is essential for advancing the discovery and production of bioactive compounds. In this study, we utilized a cumate-based inducible CRISPR interference (CRISPRi) system, CUBIC, to systematically investigate regulatory genes in S. coelicolor. By employing CUBIC-mediated repression of over 800 transcriptional factors, we conducted functional analyses to uncover their roles. Through a comprehensive library of guide RNAs, we identified dozens of novel transcription factors implicated in antibiotic biosynthesis and developmental pathways. Validation experiments demonstrated that silencing these genes significantly altered the production of actinorhodin and undecylprodigiosin, underscoring their roles in secondary metabolism. This high-throughput approach offers a robust framework for mapping regulatory networks in Streptomyces, paving the way for metabolic engineering to enhance antibiotic production and discover novel bioactive compounds.