Dr Fabrice Gielen
The overarching theme of our research is the development of novel high-throughput technologies for molecular and cellular screens, including directed enzyme evolution and single cell -omic assays. We are combining microfluidic tools with optical read-outs and state-of-the-art data analysis methods including machine learning to interrogate protein function or decipher cell population heterogeneities.
● Ultra-high-throughput screening tools
We are working on the development of microdroplet sorters for the screening of mutant protein libraries. For instance, we developed absorbance read-outs and applied it to the directed evolution of industrially relevant biocatalysts. We are exploring other types of read-outs and assess their potential to screen antimicrobial libraries, which constitute promising alternatives/complements to antibiotics.
● Multicellular Spheroid screens
In-vitro cultured cancer cells can serve as important models for preclinical testing of anti-cancer compounds. 3D cell culture formats have emerged as powerful paradigms that can closely mimic in-vivo culture conditions. However, finding optimal conditions that allow the retention of original tumor features during in vitro 3D culturing of cancer cells is challenging. This is because of the high number of individual environmental cues (biochemical, mechanical, etc) present in each cellular culture, representing a high-dimensional combinatorics problem (each cellular culture generates many variables that can be controlled precisely). A promising development in the field of 3D cell cultures is the use of microfluidic technologies which can be used to produce ultra-large numbers (up to millions) of individual cultures starting from single cells encapsulated into monodisperse hydrogel beads.
(1) Colin, P. Y., Kintses, B., Gielen, F., Miton, C. M., Fischer, G., Mohamed, M. F., Hyvonen, M., Morgavi, D. P., Janssen, D. B., Hollfelder, F., Nature Communications. 2015, 6. .
(2) Gielen, F., Hours, R., Emond, S., Fischlechner, M., Schell, U., Hollfelder, F., Proceedings of the National Academy of Sciences. 2016, 113. E7383-E7389.
(3) Gielen, F., Buryska, T., Van Vliet, L., Butz, M., Damborsky, J., Prokop, Z., Hollfelder, F., Analytical Chemistry. 2015, 87. 624-632.
(4) Kleine-Bruggeney, H., van Vliet, L. D., Mulas, C., Gielen, F., Agley, C. C., Silva, J. C. R., Smith, A., Chalut, K., Hollfelder, F., Small. 2019, 15. .
(5) Allazetta, S., Lutolf, M. P., Curr. Opin. Biotechnol. 2015, 35. 86-93.