Hostname: page-component-8448b6f56d-cfpbc Total loading time: 0 Render date: 2024-04-23T10:05:43.492Z Has data issue: false hasContentIssue false
  • English
  • Français

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.
Get access Rights & Permissions [Opens in a new window]

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
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 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alaamery, M. A., Wyman, A. R., Ivey, F. D., Allain, C., Demirbas, D., Wang, L., Ceyhan, O. and Hoffman, C. S. (2010). New classes of PDE7 inhibitors identified by a fission yeast-based HTS. Journal of Biomolecular Screening 15, 359–367.Google Scholar
Allarakhia, M. and Ajuwon, L. (2012). Understanding and creating value from open source drug discovery for neglected tropical diseases. Expert Opinion on Drug Discovery 7, 643–657.Google Scholar
An, W. F. and Tolliday, N. (2010). Cell-based assays for high-throughput screening. Molecular Biotechnology 45, 180–186.CrossRefGoogle ScholarPubMed
Bach, S., Talarek, N., Andrieu, T., Vierfond, J. M., Mettey, Y., Galons, H., Dormont, D., Meijer, L., Cullin, C. and Blondel, M. (2003). Isolation of drugs active against mammalian prions using a yeast-based screening assay. Nature Biotechnology 21, 1075–1081.Google Scholar
Bach, S., Tribouillard, D., Talarek, N., Desban, N., Gug, F., Galons, H. and Blondel, M. (2006). A yeast-based assay to isolate drugs active against mammalian prions. Methods 39, 72–77.CrossRefGoogle ScholarPubMed
Barberis, A., Gunde, T., Berset, C., Audetat, S. and Luthi, U. (2005). Yeast as a screening tool. Drug Discovery Today 2, 187–192.Google Scholar
Bender, A. T. and Beavo, J. A. (2006). Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacology Reviews 58, 488–520.CrossRefGoogle ScholarPubMed
Benko, Z., Elder, R. T., Liang, D. and Zhao, R. Y. (2010). Fission yeast as a HTS platform for molecular probes of HIV-1 Vpr-induced cell death. International Journal of High Throughput Screening 1, 151–162.Google Scholar
Bilsland, E., Pir, P., Gutteridge, A., Johns, A., King, R. D. and Oliver, S. G. (2011). Functional expression of parasite drug targets and their human orthologs in yeast. PLoS Neglected Tropical Diseases 5, e1320.Google Scholar
Bilsland, E., Sparks, A., Williams, K., Moss, H. J., de Clare, M., Pir, P., Rowland, J., Aubrey, W., Pateman, R., Young, M., Carrington, M., King, R. D. and Oliver, S. G. (2013). Yeast-based automated high-throughput screens to identify new anti-parasitic leads. Open Biology 3, 120158.Google Scholar
Castrillo, J. I. and Oliver, S. G. (2011). Yeast systems biology: the challenge of eukaryotic complexity. Methods in Molecular Biology 759, 3–28.Google Scholar
Ceyhan, O., Birsoy, K. and Hoffman, C. S. (2012). Identification of biologically active PDE11-selective inhibitors using a yeast-based high-throughput screen. Chemical Biology 19, 155–163.Google Scholar
Conti, M. and Beavo, J. (2007). Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. Annual Review of Biochemistry 76, 481–511.CrossRefGoogle ScholarPubMed
Cottier, V., Barberis, A. and Luthi, U. (2006). Novel yeast cell-based assay to screen for inhibitors of human cytomegalovirus protease in a high-throughput format. Antimicrobial Agents and Chemotherapy 50, 565–571.Google Scholar
Couplan, E., Aiyar, R. S., Kucharczyk, R., Kabala, A., Ezkurdia, N., Gagneur, J., St Onge, R. P., Salin, B., Soubigou, F., Le Cann, M., Steinmetz, L. M., di Rago, J. P. and Blondel, M. (2011). A yeast-based assay identifies drugs active against human mitochondrial disorders. Proceedings of the National Academy of Sciences, USA 108, 11989–11994.Google Scholar
Demirbas, D., Ceyhan, O., Wyman, A. R. and Hoffman, C. S. (2011). A fission yeast-based platform for phosphodiesterase inhibitor HTSs and analyses of phosphodiesterase activity. In Handbook of Experimental Pharmacology (ed. Hoffmann, F. B.), pp. 135–149. Springer-Verlag, Germany.Google Scholar
Denny, P. W., Shams-Eldin, H., Price, H. P., Smith, D. F. and Schwarz, R. T. (2006). The protozoan inositol phosphorylceramide synthase: A novel drug target which defines a new class of sphingolipid synthase. Journal of Biological Chemistry 281, 28200–28209.Google Scholar
Fernandez-Acero, T., Rodriguez-Escudero, I., Vicente, F., Monteiro, M. C., Tormo, J. R., Cantizani, J., Molina, M. and Cid, V. J. (2012). A yeast-based in vivo bioassay to screen for class I phosphatidylinositol 3-kinase specific inhibitors. Journal of Biomolecular Screening 17, 1018–1029.CrossRefGoogle Scholar
Frearson, J. A., Brand, S., McElroy, S. P., Cleghorn, L. A., Smid, O., Stojanovski, L., Price, H. P., Guther, M. L., Torrie, L. S., Robinson, D. A., Hallyburton, I., Mpamhanga, C. P., Brannigan, J. A., Wilkinson, A. J., Hodgkinson, M., Hui, R., Qiu, W., Raimi, O. G., van Aalten, D. M., Brenk, R., Gilbert, I. H., Read, K. D., Fairlamb, A. H., Ferguson, M. A., Smith, D. F. and Wyatt, P. G. (2010). N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature 464, 728–732.Google Scholar
Friedmann, Y., Shriki, A., Bennett, E. R., Golos, S., Diskin, R., Marbach, I., Bengal, E. and Engelberg, D. (2006). JX401, A p38alpha inhibitor containing a 4-benzylpiperidine motif, identified via a novel screening system in yeast. Molecular Pharmacology 70, 1395–1405.Google Scholar
Grozinger, C. M., Chao, E. D., Blackwell, H. E., Moazed, D. and Schreiber, S. L. (2001). Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. Journal of Biological Chemistry 276, 38837–38843.Google Scholar
Heby, O., Persson, L. and Rentala, M. (2007). Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas’ disease, and leishmaniasis. Amino Acids 33, 359–366.Google Scholar
Hughes, T. R. (2002). Yeast and drug discovery. Functional and Integrative Genomics 2, 199–211.Google Scholar
Ivey, F. D., Wang, L., Demirbas, D., Allain, C. and Hoffman, C. S. (2008). Development of a fission yeast-based high-throughput screen to identify chemical regulators of cAMP phosphodiesterases. Journal of Biomolecular Screening 13, 62–71.Google Scholar
Khozoie, C., Pleass, R. J. and Avery, S. V. (2009). The antimalarial drug quinine disrupts Tat2p-mediated tryptophan transport and causes tryptophan starvation. Journal of Biological Chemistry 284, 17968–17974.Google Scholar
Klein, R. D., Favreau, M. A., Alexander-Bowman, S. J., Nulf, S. C., Vanover, L., Winterrowd, C. A., Yarlett, N., Martinez, M., Keithly, J. S., Zantello, M. R., Thomas, E. M. and Geary, T. G. (1997). Haemonchus contortus: cloning and functional expression of a cDNA encoding ornithine decarboxylase and development of a screen for inhibitors. Experimental Parasitology 87, 171–184.CrossRefGoogle ScholarPubMed
Kurtz, S., Luo, G., Hahnenberger, K. M., Brooks, C., Gecha, O., Ingalls, K., Numata, K. and Krystal, M. (1995). Growth impairment resulting from expression of influenza virus M2 protein in Saccharomyces cerevisiae: identification of a novel inhibitor of influenza virus. Antimicrobial Agents and Chemotherapy 39, 2204–2209.Google Scholar
Li, W., Mo, W., Shen, D., Sun, L., Wang, J., Lu, S., Gitschier, J. M. and Zhou, B. (2005). Yeast model uncovers dual roles of mitochondria in action of artemisinin. PLoS Genetics 1, e36.Google Scholar
Limenitakis, J. and Soldati-Favre, D. (2011). Functional genetics in Apicomplexa: potentials and limits. FEBS Letters 585, 1579–1588.Google Scholar
Lipinski, C. A., Lombardo, F., Dominy, B. W. and Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 46, 3–26.Google Scholar
Marjanovic, J., Chalupska, D., Patenode, C., Coster, A., Arnold, E., Ye, A., Anesi, G., Lu, Y., Okun, I., Tkachenko, S., Haselkorn, R. and Gornicki, P. (2010). Recombinant yeast screen for new inhibitors of human acetyl-CoA carboxylase 2 identifies potential drugs to treat obesity. Proceedings of the National Academy of Sciences, USA 107, 9093–9098.Google Scholar
McCue, P. P. and Phang, J. M. (2008). Identification of human intracellular targets of the medicinal Herb St. John's Wort by chemical-genetic profiling in yeast. Journal of Agriculture and Food Chemistry 56, 11011–11017.Google Scholar
Middendorp, O., Ortler, C., Neumann, U., Paganetti, P., Luthi, U. and Barberis, A. (2004). Yeast growth selection system for the identification of cell-active inhibitors of beta-secretase. Biochimica et Biophysica Acta 1674, 29–39.Google Scholar
Mina, J. G., Mosely, J. A., Ali, H. Z., Denny, P. W. and Steel, P. G. (2011). Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain. Organic and Biomolecular Chemistry 9, 1823–1830.Google Scholar
Mina, J. G., Mosely, J. A., Ali, H. Z., Shams-Eldin, H., Schwarz, R. T., Steel, P. G. and Denny, P. W. (2010). A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase. International Journal of Biochemistry and Cell Biology 42, 1553–1561.Google Scholar
Mina, J. G., Pan, S. Y., Wansadhipathi, N. K., Bruce, C. R., Shams-Eldin, H., Schwarz, R. T., Steel, P. G. and Denny, P. W. (2009). The Trypanosoma brucei sphingolipid synthase, an essential enzyme and drug target. Molecular and Biochemical Parasitology 168, 16–23.Google Scholar
Muller, S. and Knapp, S. (2010). Targeting kinases for the treatment of inflammatory diseases. Expert Opinion on Drug Discovery 5, 867–881.Google Scholar
Munder, T. and Hinnen, A. (1999). Yeast cells as tools for target-oriented screening. Applied Microbiology and Biotechnology 52, 311–320.Google Scholar
Nagiec, M. M., Nagiec, E. E., Baltisberger, J. A., Wells, G. B., Lester, R. L. and Dickson, R. C. (1997). Sphingolipid synthesis as a target for antifungal drugs. Journal of Biological Chemistry 272, 9809–9817.Google Scholar
Seebeck, T., Sterk, G. J. and Ke, H. (2011). Phosphodiesterase inhibitors as a new generation of antiprotozoan drugs: exploiting the benefit of enzymes that are highly conserved between host and parasite. Future Medicinal Chemistry 3, 1289–1306.Google Scholar
Sibley, C. H., Brophy, V. H., Cheesman, S., Hamilton, K. L., Hankins, E. G., Wooden, J. M. and Kilbey, B. (1997). Yeast as a model system to study drugs effective against apicomplexan proteins. Methods 13, 190–207.Google Scholar
Simon, J. A. and Bedalov, A. (2004). Yeast as a model system for anticancer drug discovery. Nature Reviews Cancer 4, 481–492.Google Scholar
Siqueira-Neto, J. L., Moon, S., Jang, J., Yang, G., Lee, C., Moon, H. K., Chatelain, E., Genovesio, A., Cechetto, J., and Freitas-Junior, L. H. (2012). An image-based high-content screening assay for compounds targeting intracellular Leishmania donovani amastigotes in human macrophages. PLoS Neglected Tropical Diseases 6, e1671.Google Scholar
World Heath Organization (2012 a). http://www.who.int/neglected_diseases/diseases/en/.Google Scholar
World Heath Organization (2012 b). www.who.int/neglected_diseases/London_Declaration_NTDs.pdf.Google Scholar
Wu, G. (2010). Recent progress in phosphoinositide 3-kinases: oncogenic properties and prognostic and therapeutic implications. Current Protein and Peptide Science 11, 425–435.Google Scholar
Young, K., Lin, S., Sun, L., Lee, E., Modi, M., Hellings, S., Husbands, M., Ozenberger, B., and Franco, R. (1998). Identification of a calcium channel modulator using a high throughput yeast two-hybrid screen. Nature Biotechnology 16, 946–950.Google Scholar
Zaks-Makhina, E., Kim, Y., Aizenman, E., and Levitan, E. S. (2004). Novel neuroprotective K+ channel inhibitor identified by high-throughput screening in yeast. Molecular Pharmacology 65, 214–219.Google Scholar