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New Frontiers in Cellular Reprogramming: Exploiting Cellular Plasticity

Objective

"Our research group has worked over the years at the interface between cancer and ageing, with a strong emphasis on mouse models. More recently, we became interested in cellular reprogramming because we hypothesized that understanding cellular plasticity could yield new insights into cancer and ageing. Indeed, during the previous ERC Advanced Grant, we made relevant contributions to the fields of cellular reprogramming (Nature 2013), cellular senescence (Cell 2013), cancer (Cancer Cell 2012), and ageing (Cell Metabolism 2012). Now, we take advantage of our diverse background and integrate the above processes. Our unifying hypothesis is that cellular plasticity lies at the basis of tissue regeneration (“adaptive cellular plasticity”), as well as at the origin of cancer (“maladaptive gain of cellular plasticity”) and ageing (“maladaptive loss of cellular plasticity”). A key experimental system will be our “reprogrammable mice” (with inducible expression of the four Yamanaka factors), which we regard as a tool to induce cellular plasticity in vivo. The project is divided as follows: Objective #1 – Cellular plasticity and cancer: role of tumour suppressors in in vivo de-differentiation and reprogramming / impact of transient de-differentiation on tumour initiation / lineage tracing of Oct4 to determine whether a transient pluripotent-state occurs during cancer. Objective #2 – Cellular plasticity in tissue regeneration and ageing: impact of transient de-differentiation on tissue regeneration / contribution of the damage-induced microenvironment to tissue regeneration / impact of transient de-differentiation on ageing. Objective #3: New frontiers in cellular plasticity: chemical manipulation of cellular plasticity in vivo / new states of pluripotency / characterization of in vivo induced pluripotency and its unique properties. We anticipate that the completion of this project will yield new fundamental insights into cancer, regeneration and ageing."

Field of science

  • /natural sciences/biological sciences/cell biology/cell metabolism
  • /natural sciences/biological sciences/genetics and heredity/nucleotide
  • /medical and health sciences/clinical medicine/oncology/cancer

Call for proposal

ERC-2014-ADG
See other projects for this call

Funding Scheme

ERC-ADG - Advanced Grant

Host institution

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Address
Carrer Baldiri Reixac 10-12 Parc Scientific De Barcelona
08028 Barcelona
Spain
Activity type
Research Organisations
EU contribution
€ 2 024 047

Beneficiaries (2)

FUNDACIO INSTITUT DE RECERCA BIOMEDICA (IRB BARCELONA)
Spain
EU contribution
€ 2 024 047
Address
Carrer Baldiri Reixac 10-12 Parc Scientific De Barcelona
08028 Barcelona
Activity type
Research Organisations
FUNDACION CENTRO NACIONAL DE INVESTIGACIONES ONCOLOGICAS CARLOS III

Participation ended

Spain
EU contribution
€ 464 803
Address
Calle Melchor Fernandez Almagro 3
28029 Madrid
Activity type
Research Organisations