One of my first projects in Biophysics, Microtubule modelling and tracking was how I first entered the world of cell dynamics.

Mitotic spindle analysis and modelling

While working in the Ma group an the Albert Einstein College of Medicine (AECOM) in New York, I researched Mitotic spindle dynamics using computational modelling of the processes of Microtubule polymerisation and depolymerisation.

These models used monte-carlo simulations of the polymerisation and depolymerisation processes, together with an interaction network view of regulatory protein dynamics, to gain an understanding of the core regulatory-protein network.

As part of this work, we needed experimentally obtained reaction-rates. After watching experimental PhD candidates and Postdocs laboriously manually attempting to track various fluorescently-tagged proteins to provide quantitative data that we could use for our modelling, I made a career-course altering step. I decided to divert my efforts to tackling an obvious and growing problem in Biophysics and Biology: the rapid improvements in Imaging technologies resulting in higher resolution and vastly larger imaging datasets, meant that the manual analysis techniques previously used were simply no longer suitable for the task.

Consequently I focussed my attention on creating automated image analysis pipelines for biological experiments, initially working on Microtubule dynamics while at AECOM¹ and also including collaborators in Oxford, Dr Tommy Duncan and his then advisor Dr James Wakefiled². This work primarily used MATLAB as an analysis environment.

References

Mukherjee, S., Valencia, J.D.D., Stewman, S., Metz, J., Monnier, S., Rath, U., Asenjo, A.B., Charafeddine, R.A., Sosa, H.J., Ross, J.L. and Ma, A., 2012. Human Fidgetin is a microtubule severing the enzyme and minus-end depolymerase that regulates mitosis. Cell cycle, 11(12), pp.2359-2366.

Wainman, A., Buster, D. W., Duncan, T., Metz, J., Ma, A., Sharp, D., & Wakefield, J. G. (2009). A new Augmin subunit, Msd1, demonstrates the importance of mitotic spindle-templated microtubule nucleation in the absence of functioning centrosomes. Genes & development, 23(16), 1876-1881.

Mitotic Spindle formation

The collaboration I had started with James Wakefield continue when I joined him at the University of Exeter, as an Experimental Officer in Image Analysis. This was an independent position, working essentially as what has since been renamed a Research Software Engineer. I also made the decision to switch to Python as my core development language, as compared with e.g. MATLAB, I consider Python to be better suited for open research work due to its open-source and non-proprietary nature.

Shortly after taking up that role I continued my work on Mitotic Spindle Analysis, working with the Wakefield group to produce a range of research outputs [^hayward-1][^chen-1]³.

References

⁴

Hayward, D., Metz, J., Pellacani, C., & Wakefield, J. G. (2014). Synergy between multiple microtubule-generating pathways confers robustness to centrosome-driven mitotic spindle formation. Developmental cell, 28(1), 81-93.

⁵

Chen, J. W., Chen, Z. A., Rogala, K. B., Metz, J., Deane, C. M., Rappsilber, J., & Wakefield, J. G. (2017). Cross-linking mass spectrometry identifies new interfaces of Augmin required to localise the γ-tubulin ring complex to the mitotic spindle. Biology Open, 6(5), 654-663.

Palumbo, V., Tariq, A., Borgal, L., Metz, J., Brancaccio, M., Gatti, M., Wakefield, J.G. and Bonaccorsi, S., 2020. Drosophila Morgana is an Hsp90-interacting protein with a direct role in microtubule polymerisation. Journal of cell science, 133(2), p.jcs236786.