The utility of yeast as a tool for cell-based, target-directed high-throughput screening

• Published in: Parasitology Vol. 141; no. 1; pp. 8 - 16
• Main Authors: NORCLIFFE, J. L., ALVAREZ-RUIZ, E., MARTIN-PLAZA, J. J., STEEL, P. G., DENNY, P. W.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.01.2014
• Subjects: Biological Assay - economics; Biological Assay - utilization; cell culture; Communicable Diseases - drug therapy; cost effectiveness; Drug Delivery Systems; Drug Discovery; Drug Evaluation, Preclinical; Drugs, Investigational - pharmacology; Gene Expression; Genetic Engineering; High-Throughput Screening Assays - economics; High-Throughput Screening Assays - utilization; Humans; Neglected Diseases - drug therapy; Parasites; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; screening; Tropical Medicine; Yeasts; NTDs; HTS; Yeast
• ISSN: 0031-1820; 1469-8161; 1469-8161
• DOI: 10.1017/S0031182013000425

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.