Physicochemistry for Microbiology

DNA is known as the information medium of Life. Yet this code - the genotype - does not predetermine everything, several "interpretations" - the phenotypes - are possible. For example, our cells, so varied, originate from a single zygote and they have the same unique code. For multicellular species, the value of such an organized diversification process is obviously understandable. But why is this diversity also found in monoclonal populations of unicellular organisms? We use innovative experimental tools developed in our laboratory to explore this diversity within Escherichia coli colonies and to understand better its role and its regulation. The coexistence of these phenotypic states plays a crucial role in the development of certain infectious diseases and for antibiotic resistance strategies. The phenomenon also raises questions in the field of evolutionary biology.

One the major actual challenges in microbiology is to invent new tools for tridimensional cell culture that is physiologically more relevant than traditional studied based on cell monolayers.  The liquid core capsules that are developed in the lab offer new perspectives for cell culture since they allow a fast molecular exchange with the surrounding medium while keeping cells confined in a tridimensional space. Moreover, their high production rate opens the way to screening applications. For example, in collaboration with Curie Institute, we study the impact of the confinement on the growth of cancerous cell aggregates.

Collaborations:  UMR 144

Funding: FPGG and SANOFI

The specific selection of hematopoietic stem cells is an important matter because they can contribute to cure malignant hemopathies and certain types of cancers, and they can also produce ex vivo red blood cells (Giarratana, 2005) that can be transfused to human being (Giarratana, 2011). But these cells are rare in peripheral blood, umbilical cord blood, or bone marrow, so it is necessary to recover them specifically. It already exists a lot of sorting systems for hematopoietic stem cells but there is only one for clinical applications in Europe: the immuno-magnetic cell separation cliniMACS.
The aim of this project is to develop a new cell sorting system for clinical purposes. We want to select progenitors and hematopoietic stem cells from peripheral blood, umbilical cord blood, bone marrow, or after cellular expansion.

Collaborations: UMR_S 938 and IRHT

Industrial partnership: Bertin Technologies

Funding: ANR STREAM

Monitoring bioenergetics at a single cell level, as well as  addressing its diversity among thousands of individual cells is a challenge so far hardly achieved. However these parameters are of crucial importance to optimize the yield of production or degradation of various analytes of interest excreted by microorganisms such as bacteria, yeast or algae. Limitations reside mostly in finding probes and detectors that are sensitive enough.
We designed a probe-free method that takes advantage of the osmotically driven water flux that sets between an aqueous droplet containing a living cell towards surrounding empty ones, within a concentrated 2-D inverse emulsion. Fast diffusion of chemical species among the emulsion induces an osmotic mismatch between drops, which further relaxes from slower diffusion of water through the drop network. By measuring the rate of volume change of each drop we can deduce consumption or secretion of molecules of isolated single cells. This can in principle apply to any osmotically sensitive bioactivity, from genomic biochemistry, molecular biology to microorganism bioactivity. As a proof of concept we measured the maintenance energy of yeasts at a single cell level.

Collaborations : LBMC, Technion