A yeast synthetic network for In-vivo Reverse-engineering and Modelling Assessment (IRMA)

Cantone, Irene (2009) A yeast synthetic network for In-vivo Reverse-engineering and Modelling Assessment (IRMA). [Tesi di dottorato] (Inedito)

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Abstract

Systems Biology approaches aim to reconstruct gene regulatory networks from experimental data. Conversely, Synthetic Biology aims at using mathematical models to design novel biological ‘circuits’ (synthetic networks) in order to seed new functions inside the cell. These disciplines require quantitative mathematical models and reverse-engineering techniques. A plethora of modelling strategies and reverse-engineering approaches has being proposed during the last years. Even if successful applications have being demonstrated, at present their usefulness and predictive ability cannot still be assessed and compared rigorously. There is the pressing and yet unsatisfied need for a ‘benchmark’: a perfectly known biological circuit that can be used to evaluate pro and cons of such techniques when applied at in vivo networks. In order to address this aim, we constructed in the simplest eukaryotic organism, the yeast Saccharomyces cerevisiae, a novel synthetic network for In-vivo Reverse-engineering and Modelling Assessment (IRMA). IRMA is composed of five well-studied genes that have been assembled to regulate each other in such a way to include a variety of regulatory interactions, thus capturing the behaviour of larger eukaryotic gene networks on a smaller scale. It was designed to be isolated from the cellular environment, and to respond to galactose by triggering transcription of its genes. To demonstrate that IRMA is a unique resource to validate the System and Synthetic biology approaches, we analysed the transcriptional response of IRMA genes following two different perturbation strategies: by performing a single perturbation and measuring mRNA changes at different time points, or by performing multiple perturbations and collecting mRNA measurements at steady state. We used these data as a ‘gold standard’ to assess either the predictive ability of mathematical modelling based on differential equations and, to compare four well-established reverse engineering algorithms, NIR, TSNI, BANJO and ARACNE. We thus showed the usefulness of IRMA as the first simplified model of eukaryotic gene networks built “ad hoc” to test the power of network modelling and reverse-engineering strategies.

Tipologia di documento:Tesi di dottorato
Parole chiave:System Biology; Synthetic Biology; Modelling; Reverse-engineering; Yeast Synthetic Network
Settori scientifico-disciplinari MIUR:Area 05 Scienze biologiche > BIO/18 GENETICA
Coordinatori della Scuola di dottorato:
Coordinatore del Corso di dottoratoe-mail (se nota)
Salvatore, Francescosalvator@unina.it
Tutor della Scuola di dottorato:
Tutor del Corso di dottoratoe-mail (se nota)
Cosma, Maria Piacosma@tigem.it
di Bernardo, Diegodibernardo@tigem.it
Califano, Andreadibernardo@tigem.it
Stato del full text:Accessibile
Data:25 Marzo 2009
Numero di pagine:143
Istituzione:Università degli studi di Napoli Federico II
Dipartimento o Struttura:Telethon Institute of Genetic and Medicine (TIGEM)
Tipo di tesi:Dottorato
Stato dell'Eprint:Inedito
Scuola di dottorato:European School of Molecular Medicine - SEMM sede di Napoli
Denominazione del dottorato:PhD in Molecular Medicine - Curriculum Human Genetics
Ciclo di dottorato:XX
Numero di sistema:3323
Depositato il:13 Novembre 2009 14:40
Ultima modifica:13 Novembre 2009 14:40

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