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Actin as the Master Organizer of Nuclear Structure and Function

Actin as the Master Organizer of Nuclear Structure and Function

Objective

Unlike previously thought the nucleus is a highly compartmentalized organelle. Both the genome and processes associated with it show non-random distribution within the nucleus. This compartmentalization has a fundamental impact on nuclear processes. However, the mechanisms driving this organization are poorly understood. I hypothesize that actin plays a key role in this process. Nevertheless, the true potential of nuclear actin has not been fully appreciated, due to two fundamental open questions in this field, namely 1) what is the biological significance of nuclear actin and 2) what is the molecular mechanism by which actin operates in the nucleus? I intend to address these key questions by manipulating actin specifically in the nucleus, and by identifying nuclear actin binding partners, respectively. My lab has recently identified the nuclear import mechanism for actin, which offers us a unique tool to manipulate nuclear actin. We will therefore create cell lines with decreased/increased nuclear actin, and analyze the consequences by using cell biological and gene expression tools, combined with deep sequencing. This will disclose the genes that depend on actin for their expression, and reveal the biological significance of nuclear actin in organizing the general nuclear landscape. To unravel the mechanisms by which actin functions in the nucleus, we will implement a novel multi-readout, fluorescence microscopy screen to identify nuclear actin binding proteins, which will be analyzed by different biochemical methods. This approach will reveal how actin is connected to nuclear machineries, and what biochemical features of actin are required to power the essential nuclear processes. These techniques will significantly broaden our understanding on the nuclear functions of actin, and thus likely reveal molecular mechanisms that regulate nuclear organization, which are highly relevant to basic biological processes, such as cell differentiation and epigenetics.
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Principal Investigator

Maria Kristina Vartiainen (Dr.)

Host institution

HELSINGIN YLIOPISTO

Address

Yliopistonkatu 3
00014 Helsingin Yliopisto

Finland

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 491 484

Principal Investigator

Maria Kristina Vartiainen (Dr.)

Administrative Contact

Tuija Modinos (Ms.)

Beneficiaries (1)

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HELSINGIN YLIOPISTO

Finland

EU Contribution

€ 1 491 484

Project information

Grant agreement ID: 310930

Status

Closed project

  • Start date

    1 November 2012

  • End date

    31 August 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 491 484

  • EU contribution

    € 1 491 484

Hosted by:

HELSINGIN YLIOPISTO

Finland