- Chapel Hill, North Carolina, United States
Research Interests: Bioinformatics, Biology, Drug Discovery, Automation, Hepatitis C Virus, and 15 moreAntibiotics, HCV, Fragments, Guanine Nucleotide, Antivirals, Adenine, HCV IRES, Liquid Handling Robotics, Dual Luciferase Assays, NIH EUREKA, Internal ribosome entry site, automated QuShape, Guanine Ligand, Adenine Ligand, and Aminobenzimidazole
Research Interests: Bioinformatics, Drug Discovery, Automation, Hepatitis C Virus, Antibiotics, and 15 moreHCV, Fragments, Guanine Nucleotide, Antivirals, Adenine, HCV IRES, Liquid Handling Robotics, Dual Luciferase Assays, NIH EUREKA, Internal ribosome entry site, QuShape, automated QuShape, Guanine Ligand, Adenine Ligand, and Aminobenzimidazole
Research Interests: Bioinformatics, Drug Discovery, Automation, Hepatitis C Virus, Antibiotics, and 15 moreHCV, Fragments, Guanine Nucleotide, Antivirals, Adenine, HCV IRES, Liquid Handling Robotics, Dual Luciferase Assays, NIH EUREKA, Internal ribosome entry site, QuShape, automated QuShape, Guanine Ligand, Adenine Ligand, and Aminobenzimidazole
Research Interests:
RNA plays critical roles in diverse biological processes but has proven to be a difficult target for small molecule drug development. I addressed this challenge by developing automated SAR by SHAPE (structure-activity-relationships by... more
RNA plays critical roles in diverse biological processes but has proven to be a difficult target for small molecule drug development. I addressed this challenge by developing automated SAR by SHAPE (structure-activity-relationships by selective 2’-hydroxyl acylation analyzed by primer extension), a powerful approach for rapid and generic RNA screening against small molecule libraries. I incorporated three innovations in automated SAR by SHAPE that, together, permit effective small molecule screening campaigns against diverse RNA targets. First, I developed and programmed a magnetic bead-based SHAPE protocol on a liquid handling robot. Second, I created an automated SHAPE analysis pipeline by combining reference-based analysis and novel error-correcting algorithms. Third, I applied single-nucleotide resolution statistical hit detection to identify novel RNA ligands.
In a successful proof-of-concept for automated SAR by SHAPE, I screened nearly 500 small molecules against the Hepatitis C Virus Internal Ribosome Entry Site (HCV IRES), a large, highly structured RNA crucial for viral translation and replication. This screen identified more than 80 previously unknown IRES ligands. Significantly, several of these ligands also inhibited IRES-mediated translation in a dual luciferase assay.
*** Under the direction of Kevin Weeks, UNC-Chapel Hill.
In a successful proof-of-concept for automated SAR by SHAPE, I screened nearly 500 small molecules against the Hepatitis C Virus Internal Ribosome Entry Site (HCV IRES), a large, highly structured RNA crucial for viral translation and replication. This screen identified more than 80 previously unknown IRES ligands. Significantly, several of these ligands also inhibited IRES-mediated translation in a dual luciferase assay.
*** Under the direction of Kevin Weeks, UNC-Chapel Hill.