Regulation of mitosis through centrosomal calcium signals and coupled actin dynamics

Description

Background:

Cell division and mitosis are at the centre of development and often dysregulated in diseases associated with ageing, like cancer. Mitosis is a finally tuned process with many checkpoints to assure correct distribution of chromosomes and organelles into the two daughter cells. Our groups have recently identified two new components of the centrosomal mitosis machinery, namely the actin cytoskeleton and calcium signals, to be essential for accurate cell division. Your project will be to establish new imaging workflows to identify how actin and calcium signals are orchestrated throughout mitosis in live cells and what their function in cell division are.

Aims:

1. Identify the mitotic centrosomal Ca2+ machinery:

2. Investigate the inter-relationship between centrosomal calcium signaling and actin polymerisation during mitosis:

3. Determine the mitotic checkpoints/signals affected by centrosomal Ca2+ and actin:

Team and Training:

Your supervisor team will consist of three groups with complementary expertise. All groups will provide dedicated work plans in weekly meetings, to allow long-term planning of work and flexible working hours.  All labs have a number of senior PhD students and postdocs that will also be able to guide and support you on the journey as PhD student. In the three groups you will learn cutting edge super-resolution microscopy techniques and perform live cell imaging experiments. Large data sets of microscopy data will have to be analysed, with the expertise of the supervisor team you will develop macros and algorithms to automated the workflows. You will be taught a comprehensive repertoire of cell biological and biochemical techniques to enable the investigation into mitotic Ca2+ signals and actin dynamics. Overall the combination of techniques will give you a state-of-the-art foundation for your future independent scientific career.

Applying:

Applications should be made to project supervisors in the first instance via CV and cover letter. This is for all applications. Only when a candidate has been selected following interview will a formal online application be required. 

Availability

Open to students worldwide

Funding information

Self-funded project

Supervisors

References

Local actin nucleation tunes centrosomal microtubule nucleation during passage through mitosis. EMBO Journal 2019 Jun 3;38(11).

 

Lysosome exocytosis is required for mitosis in mammalian cells. Biochem Biophys Res Commun. 2022 Oct 20;626:211-219. doi: 10.1016/j.bbrc.2022.08.024.

 

A centrosome-localized calcium signal is essential for mammalian cell mitosis. FASEB J. 2019 Dec;33(12):14602-14610. doi: 10.1096/fj.201901662R.

 

Large scale, single-cell FRET-based glucose uptake measurements within heterogeneous populations iScience 2022 Mar 3;25(4):104023.

 

Transcription factor clusters regulate genes in eukaryotic cells. (2017) eLife Aug;6 e27451. Supervisor 3 is first author