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

Published online by Cambridge University Press:  24 April 2013

J. L. NORCLIFFE ,
E. ALVAREZ-RUIZ ,
J. J. MARTIN-PLAZA ,
P. G. STEEL  and
P. W. DENNY
J. L. NORCLIFFE
Affiliation:
Department of Chemistry and School of Biological Sciences, Biophysical Sciences Institute, University Science Laboratories, South Road, Durham, DH1 3LE
E. ALVAREZ-RUIZ
Affiliation:
GlaxoSmithKline, Platform Technologies and Science, Parque Tecnologico de Madrid, 28760 Tres Cantos, Madrid, Spain
J. J. MARTIN-PLAZA
Affiliation:
GlaxoSmithKline, Platform Technologies and Science, Parque Tecnologico de Madrid, 28760 Tres Cantos, Madrid, Spain
P. G. STEEL*
Affiliation:
Department of Chemistry and School of Biological Sciences, Biophysical Sciences Institute, University Science Laboratories, South Road, Durham, DH1 3LE
P. W. DENNY*
Affiliation:
Department of Chemistry and School of Biological Sciences, Biophysical Sciences Institute, University Science Laboratories, South Road, Durham, DH1 3LE School of Medicine, Pharmacy and Health, Durham University, Queen's Campus, Stockton-on-Tees, TS17 6BH, UK
*
*Corresponding authors: Department of Chemistry, Biophysical Sciences Institute, Durham, DH1 3LE, UK. Tel: +44 (0)191 334 3983. Fax: +44 (0)191 334 2051. E-mail: p.w.denny@durham.ac.uk, E-mail: p.g.steel@durham.ac.uk. Tel: +44 (0)191 324 2131.
*Corresponding authors: Department of Chemistry, Biophysical Sciences Institute, Durham, DH1 3LE, UK. Tel: +44 (0)191 334 3983. Fax: +44 (0)191 334 2051. E-mail: p.w.denny@durham.ac.uk, E-mail: p.g.steel@durham.ac.uk. Tel: +44 (0)191 324 2131.
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Summary

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.

Keywords

YeastHTSNTDs

Information

Type
Research Article
Information
Parasitology , Volume 141 , Issue 1: Symposia of the British Society for Parasitology volume 49 Emerging paradigms in anti-infective drug design , January 2014 , pp. 8 - 16
Copyright
Copyright © Cambridge University Press 2013 

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