Parallel genome-wide chemical genomic screens:
GCN lab has developed molecularly barcoded mutant collections of yeast, several bacterial pathogens, and the human fungal pathogen Candida albans to assay gene-drug and gene-environment interactions. The lab performs similar assays using cultured mammalian cells using large-scale shRNA screens and human gene overexpression screens.
High throughput cell-based screens:
We have developed ultra-high-throughput automated screening platforms for a wide range of exciting organisms, including yeast, E. coli, salmonella, chlamydomonas, and several archaea, and mammalian cells. The readout of these screens ranges from simple growth outputs to multiparameter imaging by microscopy and imaging cytometry.
Our lab has developed several novel NGS assays, including nucleosome-seq and barcode sequencing. In addition to performing traditional whole-genome sequencing and whole-exome sequencing, the lab has developed pathway/organelle-specific sequencing assays. Dr. Nislow directs the Faculty's sequencing center, where access is provided to a range of sequencers and sample preparation devices, including a state-of-the-art digital PCR platform.
The questions the lab has addressed and plan to address all fall under the theme of understanding how the cell takes the instructions in its DNA, i.e., its genotype, and manifests that information into phenotype in both normal and deranged circumstances. For example, the lab continues to address these questions:
How can environmental and drug stress elucidate the condition-specific function of genes?
How does the structure and architecture of the genome, manifested as chromatin, influence gene expression, and cell physiology?
Can we use genomic, chemical genomics, and genome architecture data to infer evolutionary relationships?
Finally, how can we apply the tools we develop for model organisms to human biology? Specifically, can we combine the power of next-generation sequencing and chemical biology to begin to understand the way in which gene variants affect patient responses to therapeutic intervention?