Challenges in Exploring Epithelial Regeneration: 4D Quantification of Mitotic Spindle Movement in Mother Cells

Abstract number
1468
Event
European Microscopy Congress 2020
DOI
10.22443/rms.emc2020.1468
Corresponding Email
[email protected]
Session
DHA.1 - Deep learning for analysis and interpretation of microscopy imaging data
Authors
David Dang (1), Dr Nishanth Sastry (1), Prof Viji M. Draviam (2)
Affiliations
1. King's College London, University of London
2. Queen Mary University, University of London
Keywords

spindle image analysis mark2 mitosis

Abstract text

To grow and repair tissues and organs, cells divide and multiply in numbers. During mitosis, cells form the spindle, a bulky structure with captured DNA material, which has to be precisely navigated in 3D space to arrive at its final destination before the cell divides. The cortex-microtubule interaction plays a pivotal role in force generation to exhibit different type of spindle movements. Any defects in the spindle orientation may alter tissue organization; a hallmark for cancer. 

Our lab was first to identify the significant role of MARK2 cortex-bound regulator in spindle centering in human cells – a mechanism independent of the pre-existing dynein-mediated pulling model (Zulkipli et al. 2018, Hart et al. 2019); yet the cell biological mechanisms of how the spindle undergoes rotational movements are not very well understood.

In collaboration with Sastry Group (KCL), we developed the SpinX Software, an AI-based image processing solution to investigate spatial and temporal spindle movement and rotation in spindle inhibition studies. By utilizing Deep Learning in Computer Vision and 3D modelling for precise spindle tracking, we found that MARK2/Par1b enzyme activities are crucial for spindle centering and its localisation is distinct from Dynein.


References

[2] HART, M., ZULKIPLI, I., SHRESTHA, R. L., DANG, D., CONTI, D., GUL, P., KUJAWIAK, I. AND DRAVIAM, V. M., MARK2/Par1b kinase present at centrosomes and retraction fibres corrects spindle off-centring induced by actin disassembly, OpenBiology (2019)

[2] ZULKIPLI, I., CLARK, J., HART, M., SHRESTHA, R. L., GUL, P., DANG, D., KASICHIWIN, T., KUJAWIAK, I., SASTRY, N. AND DRAVIAM, V. M., Spindle rotation in human cells is reliant on a MARK2-mediated equatorial spindle-centering mechanism, Journal of Cell Biology (2018)