title: The utility of yeast as a tool for cell-based, target-directed high-throughput screening.
abstract: Many Neglected Tropical Diseases (NTDs) have recently been subject of increased focus, particularly with relation to high-throughput screening (HTS) initiatives. These vital endeavours largely rely of two approaches, in vitro target-directed screening using biochemical assays or cell-based screening which takes no account of the target or targets being hit. Despite their successes both of these approaches have limitations; for example, the production of soluble protein and a lack of cellular context or the problems and expense of parasite cell culture. In addition, both can be challenging to miniaturize for ultra (u)HTS and expensive to utilize. Yeast-based systems offer a cost-effective approach to study and screen protein targets in a direct-directed manner within a eukaryotic cellular context. In this review, we examine the utility and limitations of yeast cell-based, target-directed screening. In particular we focus on the currently under-explored possibility of using such formats in uHTS screening campaigns for NTDs.
authors.affiliation: Department of Chemistry and School of Biological Sciences, Biophysical Sciences Institute, University Science Laboratories, South Road, Durham, DH1 3LE.
authors.forename: J L
authors.initials: JL
authors.lastname: Norcliffe
authors.affiliation: GlaxoSmithKline, Platform Technologies and Science, Parque Tecnologico de Madrid, 28760 Tres Cantos, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Alvarez-Ruiz
authors.affiliation: GlaxoSmithKline, Platform Technologies and Science, Parque Tecnologico de Madrid, 28760 Tres Cantos, Madrid, Spain.
authors.forename: J J
authors.initials: JJ
authors.lastname: Martin-Plaza
authors.affiliation: Department of Chemistry and School of Biological Sciences, Biophysical Sciences Institute, University Science Laboratories, South Road, Durham, DH1 3LE.
authors.forename: P G
authors.initials: PG
authors.lastname: Steel
authors.affiliation: Department of Chemistry and School of Biological Sciences, Biophysical Sciences Institute, University Science Laboratories, South Road, Durham, DH1 3LE.
authors.forename: P W
authors.initials: PW
authors.lastname: Denny
mesh_terms: D001681:Biological Assay / Q000191:economics / Q000706:statistics & numerical data*; D003141:Communicable Diseases / Q000188:drug therapy; D016503:Drug Delivery Systems; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000494:pharmacology; D015870:Gene Expression; D005818:Genetic Engineering; D057166:High-Throughput Screening Assays / Q000191:economics / Q000706:statistics & numerical data*; D006801:Humans; D058069:Neglected Diseases / Q000188:drug therapy; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014330:Tropical Medicine
chemical_list: D015507:Drugs, Investigational; D015800:Protozoan Proteins