CORDIS
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CORDIS

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Composition and dynamics of stress granules in cerebral organoid models of frontotemporal dementia

Project information

Grant agreement ID: 897137

Status

Ongoing project

  • Start date

    1 June 2020

  • End date

    31 May 2022

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 174 167,04

  • EU contribution

    € 174 167,04

Coordinated by:

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH

Austria

Objective

Frontotemporal dementia (FTD) is the second most common form of dementia. A pathological hallmark is the formation of protein aggregates that consist mainly of Tau or TDP43. Patients suffer from the degeneration of the frontal and temporal lobes with no effective treatments being available. The recent advancement of 3D brain organoid cultures grown from embryonic stem cells offer new possibilities to study disease mechanisms of neurological disorders and help validate therapeutic interventions. I therefore propose to generate the first cerebral organoid models of FTD. The new models will first be thoroughly characterized by immunohistochemical stainings and biochemical analysis. Furthermore, I will determine neuroaxonal degeneration, visualize protein aggregates and their cell-to-cell spreading and analyze the nucleation of the pathological protein conformation. In addition, I will determine if FTD-organoids recapitulate the brain region- and cell type-specific vulnerability that are observed in patients. FTD has also been linked to aberrant phase transition of proteins that can lead to disturbances in proteome and RNA homeostasis. However, molecular mechanisms and consequences of this processes in disease conditions remain largely unknown. I therefore propose to study the dynamics and molecular composition of stress granules, which are functional biomolecular condensates that arise through liquid-liquid phase separation during stress conditions, in FTD cerebral organoids. Disease-associated changes in stress granule dynamics and thus disturbances in RNA metabolism and regulation of neuronal translational might result in the lack of essential neuronal proteins. I will therefore identify and quantify key mRNA and protein components of neuronal stress granules in brain organoids. In summary, this project will provide new mechanistic insights into disease mechanisms of FTD and open new possibilities of therapeutic interventions.

Coordinator

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH

Address

Dr Bohrgasse 3
1030 Wien

Austria

Activity type

Private for-profit entities (excluding Higher or Secondary Education Establishments)

EU Contribution

€ 174 167,04

Project information

Grant agreement ID: 897137

Status

Ongoing project

  • Start date

    1 June 2020

  • End date

    31 May 2022

Funded under:

H2020-EU.1.3.2.

  • Overall budget:

    € 174 167,04

  • EU contribution

    € 174 167,04

Coordinated by:

INSTITUT FUER MOLEKULARE BIOTECHNOLOGIE GMBH

Austria