DEPTH

DEsigning new Paths in The differentiation Hyperspace

Coordinatore	UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Italy [IT]
Totale costo	2˙639˙804 €
EC contributo	2˙639˙804 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2012-ADG_20120314
Funding Scheme	ERC-AG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-04-01   -   2018-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA  Organization address address: VIA ORAZIO RAIMONDO 18 city: ROMA postcode: 173 contact info Titolo: Prof. Nome: Giovanni Cognome: Cesareni Email: send email Telefono: 390673000000 Fax: 39062023500	IT (ROMA)	hostInstitution	2˙639˙804.00
2	UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA  Organization address address: VIA ORAZIO RAIMONDO 18 city: ROMA postcode: 173 contact info Titolo: Prof. Nome: Giuseppe Cognome: Novelli Email: send email Telefono: 390673000000 Fax: 39067236605	IT (ROMA)	hostInstitution	2˙639˙804.00

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 Obiettivo del progetto (Objective)

'The adult human organism contains heterogeneous reservoirs of pluripotent stem cells characterized by a diversified differentiation potential. Understanding their biology at a system level would advance our ability to selectively activate and control their differentiation potential. Aside from the basic implications this would represent a substantial progress in regenerative medicine by providing a rational framework for using small molecules to control cell trans-determination and reprogramming. Here we propose a combined experimental and modelling approach to assemble a predictive model of mesoderm stem cell differentiation. Different cell states are identified by a vector in the differentiation hyperspace, the coordinates of the vector being the activation levels of a large number of nodes of a logic model linking the cell signalling network to the transcription regulatory network. The premise of this proposal is that differentiation is equivalent to rewiring the cell regulatory network as a consequence of induced perturbation of the gene expression program. This process can be rationally controlled by perturbing specific nodes of the signalling network that in turn control transcription factor activation. We will develop this novel strategy using the mesoangioblast ex vivo differentiation system. Mesoangioblasts are one of the many different types of mesoderm stem/progenitor cells that exhibit myogenic potential. Ex vivo, they readily differentiate into striated muscle. However, under appropriate conditions they can also differentiate, into smooth muscle and adipocytes, albeit less efficiently. We will start by assembling, training and optimizing different predictive models for the undifferentiated mesoangioblast. Next by a combination of experiments and modelling approaches we will learn how, by perturbing the signalling models with different inhibitors and activators we can rewire the cell networks to induce trans-determination or reprogramming.'