Microbial Functional Genomics and Synthetic Biology

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Studying the genetic underpinnings of fungal biology and drug resistance has been hindered by genetic limitations associated working with this group of microbes, including its diploid nature, incomplete sexual cycle and atypical codon usage. CRISPR-Cas-based technologies have now revolutionized our ability to perform targeted genome editing in these microorganisms. This CRC research program will develop novel CRISPR-based biotechnologies to establish large-scale genetic libraries for functional analysis in the prevalent fungal pathogen, Candida albicans. Like other fungal infections, C. albicans is notoriously challenging to treat and represents a growing public health concern. This research will exploit a novel CRISPR interference (CRISPRi)-based genetic repression system for comparative functional genomic analysis of drug resistance in C. albicans in order to identify important genetic modulators of drug resistance, and further expand CRISPRi technology towards genome-wide functional genomic screening platform for antifungal drug sensitivity. Additionally, this research program will develop and optimize two novel platforms: a CRISPR activation (CRISPRa)-based genetic overexpression system, and a targeted CRISPR base editor system for diverse genetic applications in fungal species. Collectively, this CRC research program will apply leading edge CRISPR-based functional genomics to current and emerging fungal pathogens to decipher the genetic mechanisms mediating drug resistance.