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Role of spindle asymmetry components in a multinucleated cell

English title Role of spindle asymmetry components in a multinucleated cell
Applicant Philippsen Peter
Number 112688
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Mikrobiologie Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Cellular Biology, Cytology
Start/End 01.04.2006 - 30.09.2010
Approved amount 467'685.00
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Keywords (6)

Filamentous fungus; Multinucleated cells; Asyndronous nuclear divisions; Nuclear dynamics; spindle asymmetri; microtubules

Lay Summary (English)

Lead
Lay summary
1. SUMMARY
The division plane in most eukaryotic cells is determined by the position of the mitotic spindle. The control network of spindle positioning therefore regulates whether a cell divides symmetrically or asymmetrically. Such control does not seem to be important in filamentous ascomycetes, because a nuclear division in the long multinucleated cells(hyphae) triggers neither a cell division nor the formation of a septum.
Unexpectedly, our genome analysis of the filamentous fungus Ashbya gossypii revealed orthologues of all known Saccharomyces cerevisiae proteins involved in spindle positioning and exit from mitosis including checkpoint components (Dietrich et al. 2004). This research proposal describes experiments designed to understand the role of these A. gossypii orthologous proteins. They may have evolved to support characteristic features of dynamic behavior of nuclei in growing A. gossypii hyphae:
controlled distribution, long-range migration, oscillation, by-passing, and asynchronous mitosis. Based on preliminary data, we hypothesize that the interconnection of nuclei by long cytoplasmic microtubules, in addition to the cortical contacts by short cytoplasmic microtubules, are of prime importance for many aspects of nuclear dynamics in this model filamentous fungus, and that asymmetries of microtubule organization centers (MTOC) are needed to build this multinuclear control network.
Using time-lapse microscopy, combined with cell biological and functional genomics approaches, we will test these ideas through studying the localization, dynamics, and mutant versions of homologues of MTOC components and putative asymmetry regulators. This work will further elucidate the plasticity of nuclear dynamics in eukaryotes through uncovering unique functions for conserved regulators.

SPECIFIC AIMS
A. Determination of the positions of the old and new MTOC in relation to the growth direction of A. gossypii hyphae, and comparison of the location of S. cerevisiae asymmetry components with those of conserved orthologuesof A. gossypii.
B. Identification of the molecular controls for nuclear distribution, oscillation, by-passing, and spindle orientation in A. gossypii, and study of these controls in young hyphae and in fast elongating mature hyphae.
C. Characterization of the role in A. gossypii of homologues of S.cerevisiae cortical mother cell and bud markers.
D. Synchronisation of nuclear divisions in A. gossypii to determine, with the help of Affimetrix Ashbya DNA chips, the transcription profiles of genes involved in nuclear dynamics at different developmental stages.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
100734 Regulation of asynchronous mitoses in a multinucleated cell 01.04.2003 Project funding (Div. I-III)

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