Analysis and modelling of lysosomal distribution and dynamics
Internship title: Analysis and modelling of lysosomal distribution and dynamics
Name: Curie Institute
Address: 12 rue Lhomond
Name: Bruno Goud
Phone number: 0156246398
Name: Kristine Schauer
Phone number: 0156246404
Subject Keywords: Modelling
Dynamic systems theory
Tools and methodologies: Confocal spinning disk live imaging
Dynamic system theory
Summary of lab’s interests: We have developed a computational tool based on the micropatterning technique and density estimation using kernel-based algorithms to visualize the global organization of endomembranes. Our recent work using this approach has highlighted the role of cell adhesion in the topology of endocytosis and signaling. Ongoing studies aim at identifying molecular motors of the myosin and kinesin families that sustain the steady-sate organization of endomembranes and at detecting changes of this organization in cancer cells.
Project summary: Lysosomes are essential organelles of the eukaryotic cell responsible of lytic activity. Usually, an eukaryotic cell has several hundreds of lysosomes with a non-random spatial distribution. At resting state, lysosomal distribution is a non-equilibrium steady state (NESS), which means that the global distribution does not changed while lysosomes continue to move individually. Moreover, after a perturbation, it seems that there is a spontaneous recovery of the steady state distribution. How do lysosomes spontaneously go back to their steady-state distribution after a perturbation?
First, the project will focus on the characterization of lysosomal dynamics in order to evaluate the centrifuge and centripetal flux, as well as exocytosis rate and biogenesis rate. We will assess these issues using a confocal spinning disk microscope that is specialized for live-imaging. Moreover, lysosomal positioning will be perturbed by an optogenetic system coupling lysosomes to molecular motors using light. This system will allow us to observe how the cell comes back to its steady state. Second, we will model lysosomal distribution. Especially, this question will be addressed thanks to dynamic systems theory in order to write mathematical model and simulate it. We aim at determining whether a stable/attractive fixed point exists for the modelled system and at comparing the dynamics after a perturbation between the model and the observed data.
Interdisciplinary aspect of the project: This project is interdisciplinary because it combine classic cell biology (live-imaging, cell culture) with physics/modelling (dynamic systems theory). The main aim of this project is to understand a biological observation (why lysosomal distribution is stable ?) with modelling eyes (there is a attractive/fixed point in the system ?).