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DualSpindleAssembly

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Defining the mechanism of the dual spindle assembly and alignment in the mammali...

Defining the mechanism of the dual spindle assembly and alignment in the mammalian zygote The first embryonic division after fertilization is essential for development of the organism and has to promote the union of the parental genomes. My host lab recently showed that in mammalian zygotes two bipolar spindles form, w... ver más

31/05/2023

EMBL

175K€

Presupuesto del proyecto: 175K€

Líder del proyecto

EUROPEAN MOLECULAR BIOLOGY LABORATORY No se ha especificado una descripción o un objeto social para esta compañía.

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2023-05-31

MSCA-IF-2020: Individual Fellowships

I+D

Cerrada hace 4 años

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

1 Participantes

EMBL

174.81K€ | Lider

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Duración del proyecto: 25 meses Fecha Inicio: 2021-04-08
Fecha Fin: 2023-05-31

Líder del proyecto

EUROPEAN MOLECULAR BIOLOGY LABORATORY No se ha especificado una descripción o un objeto social para esta compañía.

Presupuesto del proyecto 175K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The first embryonic division after fertilization is essential for development of the organism and has to promote the union of the parental genomes. My host lab recently showed that in mammalian zygotes two bipolar spindles form, which first independently congress the maternal and paternal chromosomes and then must be aligned in parallel for a faithful division. The novel dual spindle assembly provided a likely rationale for erroneous divisions into more than two blastomeric nuclei observed in human fertility treatment. Indeed, preventing the alignment of the two spindles gives rise to multi-nucleated two-cell embryos also in mice. Due to its recent discovery and the difficulty of imaging in the light sensitive zygote, dual spindle assembly and function remains elusive. It is for example unclear what the contribution of cytoplasmic versus chromosomal microtubule (MT) nucleation is for forming two spindles and why spindle alignment is error-prone and variable between different mammals. Recent advances in microscopy in my host lab now enable me to address these questions. In my project, I will dissect the mechanism of dual spindle assembly and function by combining light sheet microscopy, computational image analysis, and molecular perturbation. To achieve this, I will perform 4D imaging of live mouse zygotes at high resolution that allows me to track individual nucleation sites as well as MT tips. This will allow me to generate the first spatial map of MT nucleation and assess what the contribution of the two MT populations for dual spindle assembly is. Moreover, I will test which MT nucleation pathway is essential for dual spindle assembly by molecular perturbations. Finally, I will check if errors in spindle alignment are the cause of parental genome loss, by identifying the key alignment factors and validate them in model organisms with different alignment fidelities. Thus, my studies will improve our understanding of cell division in mammals and human infertility.

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