I am interested in the mechanics of cell division in tissues. The correct orientation of cell division is essential for cell fate decisions during development and misorientation can cause diseases such as cancer. Several mechanisms of division orientation have been characterised recently, however it remains unclear how these molecular mechanisms respond to mechanical stresses that tissues are exposed to. Here, in the Charras Lab, I am interested in studying how mechanical forces applied on the tissue level affect the orientation of cell divisions. To tackle this, I will use suspended epithelial monolayers, an experimental system previously developed in the lab. Using this system I hope to gain insights into the dynamics of cell division in tissues under stress and an understanding of the molecular mechanisms involved in force transmission and spindle orientation.
I did my PhD with Stephan Grill at the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, where I was investigating the dynamics of transcription and pausing of different eukaryotic RNA polymerases using a single-molecule approach.
RNA polymerases are enzymes responsible for copying the genetic information stored in the DNA into RNA. Transcription elongation is often interrupted with pauses and backtracking, a process in which the polymerase moves in the opposite direction of forward elongation. Since a backtracked polymerase stops producing RNA, it is essential that it recovers from the backtrack and continues elongation. A central focus of my PhD research has been to characterise the dynamics of transcription elongation and backtrack recovery of two different eukaryotic RNA polymerases, Pol I and Pol II. To this end, I developed a new optical tweezers assay to study backtrack recovery and showed that Pol I and Pol II use different strategies to recover from different backtrack depths: short backtracks are recovered by 1D diffusion while intermediate ones recover by transcript cleavage. Furthermore, I showed that Pol I and Pol II have comparable diffusion rates and that differences in backtrack recovery stem mainly from differences in cleavage activities (Lisica et al. 2016). Finally, in collaboration with Édgar Roldán (MPI-PKS, Dresden, Germany), we modelled the polymerase backtrack recovery as a stochastic resetting process and found that the choice of a recovery pathway is determined by a kinetic competition between 1D diffusion and cleavage (Roldán, Lisica et al. 2016).