Dynamics of the peri-nuclear actomyosin network for correct chromosome positioning in early mitosis

• Funding – self-funded/externally sponsored applicants (PhD Fees can be found here)
• Applications are accepted year round
• Standard Entry dates – January and September
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline. 

To maintain genetic integrity, human cells must inherit the whole set of chromosomes without any loss or excess when the cell division takes place. To ensure this process, each copy of duplicated chromosomes must segregate to opposite spindle poles during mitosis. This process relies on the correct interaction of chromosomes with the mitotic spindle. Defects in this process lead to numerical chromosomal instability (N-CIN), which is closely associated with chemotherapy resistance and poor prognosis of cancers.

The Tanaka group and others have recently discovered a novel perinuclear actomyosin network formed in early mitosis (PANEM). The PANEM rapidly assembles in early mitosis (prophase), shows contraction immediately after the nuclear envelope breakdown (NEBD), and pushes chromosomes inward to facilitate their interaction with the mitotic spindle (Booth et al 2019). The defects in PANEM assembly or contraction lead to a delay in chromosome congression to a metaphase plate and frequent errors in chromosome segregation. Intriguingly, some cancer cells (e.g. HeLa) with N-CIN lack the PANEM.

In this project, we will address molecular mechanisms facilitating the rapid PANEM assembly in prophase and identify the trigger of PANEM contraction immediately after NEBD. These dynamic characters of the PANEM are crucial for chromosome positioning in early mitosis to ensure correct chromosome segregation later in mitosis. Moreover, we will address whether the lack of PANEM in cancer cells with N-CIN plays a causative role in N-CIN in these cancer cells. The student, who works on this project, will learn methods of advanced live-cell imaging, AI-driven image analyses, CRISPR gene editing and mass-spectrometry.

If you have any questions about this project, please do not hesitate to contact Prof Tomo Tanaka ([email protected]).

Reference

Booth AJR., Yue, Z, Eykelenboom JK, Luxton GWG, Hochegger H & Tanaka TU Contractile actomyosin network on nuclear envelope remnants positions chromosomes for mitosis. eLife 8, e46902 (2019).

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