Erik Maikranz

Project title: MASiD:
Measuring antibiotic susceptibility in droplets: From single cells to populations

Host Institution: École polytechnique (l’X)

Host Supervisor: Prof. Dr. Charles Baroud

Co-host Institution: École Polytechnique Fédérale de Lausanne (EPFL)

Co-host Supervisor: Prof. Dr. Francois Gallaire

Summary project: While the occurrence of antibiotic resistance is becoming a major concern for public health, studies investigating how the susceptibility of single cells and their lineages is related to the susceptibility of entire populations remain scarce. This is due to technical difficulties in performing large amounts of experiments and observing single cells and their progeny. The use of microfluidic droplets as micro-reactors helps to overcome these difficulties. We plan to implement an automated image analysis pipeline to obtain thousands of individual growth curves for colonies starting from single cells. From this, we are able to construct the time-dependent probability distribution of the number of cells for various antibiotic concentrations. This distribution will be compared to predictions from the to be developed stochastic birth-death model, involving the response to antibiotics and probabilistic parameters representing biological variability. We will thus address if cells escape antibiotics due to stochasticity at the individual level or as a result of biological variability. The droplet measurements will then be related to classical bulk measurements, which enables us to quantify collective effects present in the bulk culture. The aim is to establish this microfluidic platform as the standard for measuring bacterial response to antibiotics and in a second step to combine this platform and theoretical model to create a bacterial susceptibility database clarifying the interdependencies of stochasticity and inheritable biological variability.

Erik Maikranz