PKS

In a modular PKS such as the 6-deoxyerythronolide B synthase, sets of catalytic domains are organized into modules. The catalytic domains from a given module cooperate to synthesize polyketides via a thiotemplate mechanism similar to that of fatty acid synthesis. The nascent polyketide intermediates are then passed down to the next module in the protein assembly line. Organized into three polypeptides (DEBS1-3), DEBS consists of six catalytic modules, each containing a unique set of covalently linked catalytic domains. Together, the six modules of this megasynthase (approximated 2MDa) produce 6-deoxyerythronolide B (6-dEB), the polyketide portion of the antibiotic erythromycin.

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Celiac Disease

Celiac Disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted from of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy.

Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease.

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Antiviral

Broad-spectrum antiviral drugs targeting host processes could potentially treat a wide range of viruses while reducing the likelihood of emergent resistance. Despite great promise as therapeutics, such drugs remain largely elusive. Here we used parallel genome-wide high-coverage short hairpin RNA (shRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screens to identify the cellular target and mechanism of action of GSK983, a potent broad-spectrum antiviral with unexplained cytotoxicity.

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