Prof Georges Debrégeas

Motile animals use sensory cues to navigate towards environments where there are more likely to obtain food, find mates or to avoid predators. Sensory-driven navigation relies on a closed-loop mechanism between motor action and motor-induced sensory inputs. At each instant, multiple sensory cues have to be integrated to bias the forthcoming motor command. The student will thoroughly and quantitatively characterize the behavioral algorithm underlying sensory-driven navigation in zebrafish larvae. The animals will be 5-10 days old, as this age is amenable to whole-brain functional imaging. The project will focus on both phototaxis (navigation towards a light source) and thermotaxis (navigation relative to a thermal gradient). Two experimental platforms will be set up. 1. Freely swimming larvae will be video-monitored and submitted to whole-field visual stimuli. The visual stimulation will be locked in real-time on the animal’s orientation and/or position in space. This will allow in particular to separately probe the effect of stereo (difference in illumination between both eyes) and uniform (total illumination on both eyes) visual cues. For thermally-driven navigation, the animal will be allowed to freely explore a large environment in which a constant thermal gradient is imposed.e 2. Experiments will be reproduced in a virtual-reality setting. In this case, the animal is partially restrained in agarose with its tail free. Monitoring the tail movement will provide access to its virtual displacement, on which the visual and/or thermal stimuli will be locked. These behavioral experiments will be analysed in order to describe the animal’s navigation as a sensory-biased random walk. For more information see: https://www.smartnets-etn.eu/behavioral-characterization-of-sensory-driven-nagivation-in-zebrafish-larvae/

3D Printing Cellular Communities: Mammalian Cells, Bacteria, And Beyond

While the motion and collective behavior of cells are well-studied on flat surfaces or in unconfined liquid media, in most natural settings, cells thrive in complex 3D environments. Bioprinting processes are capable of structuring cells in 3D and conventional bioprinting approaches address this challenge by embedding cells in bio-degradable polymer networks. However, heterogeneity in network structure and biodegradation often preclude quantitative studies of cell behavior in specified 3D architectures. Here, I will present a new approach to 3D bioprinting of cellular communities that utilizes jammed, granular polyelectrolyte microgels as a support medium. The self-healing nature of this medium allows the creation of highly precise cellular communities and tissue-like structures by direct injection of cells inside the 3D medium. Further, the transparent nature of this medium enables precise characterization of cellular behavior. I will describe two examples of my work using this platform to study the behavior of two different classes of cells in 3D. First, I will describe how we interrogate the growth, viability, and migration of mammalian cells—ranging from epithelial cells, cancer cells, and T cells—in the 3D pore space. Second, I will describe how we interrogate the migration of E. coli bacteria through the 3D pore space. Direct visualization enables us to reveal a new mode of motility exhibited by individual cells, in stark contrast to the paradigm of run-and-tumble motility, in which cells are intermittently and transiently trapped as they navigate the pore space; further, analysis of these dynamics enables prediction of single-cell transport over large length and time scales. Moreover, we show that concentrated populations of E. coli can collectively migrate through a porous medium—despite being strongly confined—by chemotactically “surfing” a self-generated nutrient gradient. Together, these studies highlight how the jammed microgel medium provides a powerful platform to design and interrogate complex cellular communities in 3D—with implications for tissue engineering, microtissue mechanics, studies of cellular interactions, and biophysical studies of active matter.

Tutorial talk: Bacterial Chemotaxis

Integrative modeling of Paramecium, a swimming neuron

Paramecium is a unicellular organism that swims in fresh water using cilia. When it is stimulated (mechanically, chemically, optically, thermally, etc), it often swims backward then turns and swims forward again: this is called the avoiding reaction. This reaction is triggered by a calcium-based action potential. For this reason, it enjoyed a period of glory in the 1970s as a model organism for neuroscience. I will describe the behavior and electrophysiology of this “swimming neuron”, then I will present our ongoing attempts at developing an integrative quantitative model of Paramecium.