Mednarodni projekti
Functional genomics of complex regulatory networks from yeast to human: cross-talk of sterol homeostasis and drug metabolism
Raziskovalci (1)
| št. |
Evidenčna št. |
Ime in priimek |
Razisk. področje |
Vloga |
Obdobje |
Štev. publikacijŠtev. publikacij |
| 1. |
06013 |
dr. Damjana Rozman |
Biokemija in molekularna biologija |
Vodja |
2005 - 2008 |
887 |
Organizacije (4)
Povzetek
The vision of STEROLTALK is to develop a global approach by combining dedicated functional genomic tools, three model organisms and in silico modelling, for the discovery of new drugs targets, new chemical entities and therapeutic strategies. Regulatory networks in human, mouse and S. cerevisiae will be assessed through integrative analysis of transcriptome, proteome, metabolome and by yeast engineering. This will allow for the first time to dechipher the multi-level response of cholesterol homeostasis to known and candidate drugs, and its modulation in pathologies. Typical investigation targets will be animal and adult human livers and primary hepatocytes. The first task of our STREP is to develop original tools for functional genomic analyses of drug-modulated responses of STEROLTALK genes, proteins and metabolites in biological models. Tools include a dedicated microarray, antibody set, siRNA knockouts, humanized yeast and database. Deposited analytical data will be evaluated by numerous bioinformatic approaches, to assist in building relevant in silico models with predictive values, ready for implementation in novel drug discovery strategies. In silico model prediction will allow for the first time to identify potential cholesterol homeostasis-related targets that will be validated in vivo in biological models by the original STEROLTALK tools. This will eventually lead to substantial breakthroughs with numerous applications in the fields of drug discovery, development of diagnostic procedures, providing also new tools for pharmacological interventions. The project features multiple functional genomics challenges. In tackling these, it will lead to breakthroughs in functional genomics tools development and will drastically advance our understanding of the cross talk of drugs and cholesterol homeostasis.
