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IntrinsicReceptors

Financiado

Intrinsic autophagy receptors: identity and cellular mechanisms.

Macromolecular complexes (MC) are cellular machines that perform a wide array of vital tasks. They operate in a controlled, coordinated fashion within the crowded environment of the cell. Accumulation of dysfunctional MCs leads to... ver más

30/09/2027

MPG

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

MAXPLANCKGESELLSCHAFT ZUR FORDERUNG DER WISSE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-07-20

ERC-2021-STG: ERC STARTING GRANTS Scope:Objectives

I+D

Cerrada hace 3 años

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Información adicional privada

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

1 Participantes

MPG

1.50M€ | Lider

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Duración del proyecto: 62 meses Fecha Inicio: 2022-07-20
Fecha Fin: 2027-09-30

Líder del proyecto

MAXPLANCKGESELLSCHAFT ZUR FORDERUNG DER WISSE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Descripción del proyecto Macromolecular complexes (MC) are cellular machines that perform a wide array of vital tasks. They operate in a controlled, coordinated fashion within the crowded environment of the cell. Accumulation of dysfunctional MCs leads to age-related diseases. Despite recent technological advancements, it still remains elusive for many of them how excess or dysfunctional MCs are sensed and removed. I have recently established a role of intrinsic receptors in degradation of the nuclear pore complex and the clathrin-mediated endocytosis machinery by selective autophagy. Intrinsic receptors represent functional subunits of the macromolecular machine but can if needed recruit the autophagy machinery to engulf and degrade the complex. As such intrinsic receptors provide an in-built quality control function that monitors the assembly state and/or functionality of macromolecular machines. I hypothesize that this is a conserved and widely used principle existing within various MCs and that there is a common, yet unexplored, regulatory pathway underlying the intrinsic receptors’ mode of action. In the proposed project, I will employ a combination of genetic screening, mass spectrometry and cryo-electron tomography to systematically define intrinsic receptors and their working principles in cells. I will use systematic discovery approaches to determine how many MCs contain intrinsic receptors, how the degradation of intrinsic receptors and their cargo is regulated, and how this is orchestrated with autophagosome biogenesis. My results will not only provide insights into a novel cellular quality-control mechanism but also unravel novel aspects of selective autophagosome biogenesis. Importantly, both accumulation of dysfunctional complexes and impairment of autophagy are linked to aging and age-related diseases. Therefore, my results will contribute to understand the role of autophagy in these processes and have the potential to provide new pharmacological therapeutic avenues.

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