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Mechanobiology of nuclear import of transcription factors modeled within a bioen...

Mechanobiology of nuclear import of transcription factors modeled within a bioengineered stem cell niche. Many therapeutic applications of stem cells require accurate control of their differentiation. To this purpose there is a major ongoing effort in the development of advanced culture substrates to be used as synthetic niches for th... ver más

31/07/2020

POLIMI

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

POLITECNICO DI MILANO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Ver 3 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-07-31

ERC-CoG-2014: ERC Consolidator Grant

I+D

Cerrada hace 10 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

3 Participantes

POLIMI

1.80M€ | Lider

GABINETE DE SOFTWARE EMPRESA...

473.03K€ | Participante

IRFMN

100.50K€ | Participante

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Duración del proyecto: 63 meses Fecha Inicio: 2015-04-01
Fecha Fin: 2020-07-31

Líder del proyecto

POLITECNICO DI MILANO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Many therapeutic applications of stem cells require accurate control of their differentiation. To this purpose there is a major ongoing effort in the development of advanced culture substrates to be used as synthetic niches for the cells, mimicking the native ones. The goal of this project is to use a synthetic niche cell culture model to test my revolutionary hypothesis that in stem cell differentiation, nuclear import of gene-regulating transcription factors is controlled by the stretch of the nuclear pore complexes. If verified, this idea could lead to a breakthrough in biomimetic approaches to engineering stem cell differentiation. I investigate this question specifically in mesenchymal stem cells (MSC), because they are adherent and highly mechano-sensitive to architectural cues of the microenvironment. To verify my hypothesis I will use a combined experimental-computational model of mechanotransduction. I will a) scale-up an existing three-dimensional synthetic niche culture substrate, fabricated by two-photon laser polymerization, b) characterize the effect of tridimensionality on the differentiation fate of MSC cultured in the niches, c) develop a multiphysics/multiscale computational model of nuclear import of transcription factors within differentially-spread cultured cells, and d) integrate the numerical predictions with experimentally-measured import of fluorescently-labelled transcription factors. This project requires the synergic combination of several advanced bioengineering technologies, including micro/nano fabrication and biomimetics. The use of two-photon laser polymerization for controlling the geometry of the synthetic cell niches is very innovative and will highly impact the fields of bioengineering and biomaterial technology. A successful outcome will lead to a deeper understanding of bioengineering methods to direct stem cell fate and have therefore a significant impact in tissue repair technologies and regenerative medicine.

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