Head of Mechanism in Chemistry and Biology Group
Departments and Institutes
My group is interested in gaining a fundamental understanding of the principles responsible for molecular recognition processes in chemistry and biology. We probe whether these principles enable us to describe, manipulate and ultimately make functional molecules. Using an eclectic mix of techniques (including kinetic measurements, organic synthesis, biophysical analysis and microengineering) we extend the mechanistic lessons learned to potential applications in biotechnology, chemistry and medicine. In particular we are excited about the potential of pico- to nanolitre mircrodroplets to provide a quantitative high-throughput system that provides insight not only into one reaction at a time, but - by way of massive multiplexing - lets us study millions of samples in one go.
• van Loo, B.; Jonas, S.; Babtie, A. C.; Benjdia, A.; Berteau, O.; Hyvönen, M.; Hollfelder, F., An efficient, multiply promiscuous hydrolase in the alkaline phosphatase superfamily. Proc. Natl Acad. Sci USA 2010, 107 (7), 2740-5.
• Villiers, B. R.; Hollfelder, F., Narrowing the Size Selectivity of an A-domain by Directed Evolution. Chemistry & Biology 2011,18(10):1290-9.
• Kintses, B.; Hein, C.; Mohamed, M. F.; Fischlechner, M.; Courtois, F.; Lainé, C.; Hollfelder, F. Chemistry & Biology 2012, Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution, 19(8):1001-9.
• Diamante, L.; Gatti-Lafranconi, P.; Schaerli, Y.; Hollfelder, F., In vitro affinity screening of protein and peptide binders by megavalent bead surface display. Protein Eng Des Sel 2013, 26(10):713-24.
• Mohamed, M.F. & Hollfelder, F. Efficient, crosswise catalytic promiscuity among enzymes that catalyze phosphoryl transfer. Biochim Biophys Acta 2013, 1834, 417-2.
• Kwok, A., Eggimann, G.A., Reymond, J.L., Darbre, T. & Hollfelder, F. Peptide dendrimer/lipid hybrid systems are efficient DNA transfection reagents: structure-activity relationships highlight the role of charge distribution across dendrimer generations. ACS Nano 2013, 7, 4668-82.
• Gielen, F.; van Vliet, L.; Koprowski, B. T.; Devenish, S. R.; Fischlechner, M.; Edel, J. B.; Niu, X.; Demello, A. J.; Hollfelder, F., A Fully Unsupervised Compartment-on-Demand Platform for Precise Nanoliter Assays of Time-Dependent Steady-State Enzyme Kinetics and Inhibition. Anal Chem 2013, 85(9):4761-9.
• Golicnik, M.; Olguin, L. F.; Feng, G.; Baxter, N. J.; Waltho, J. P.; Williams, N. H.; Hollfelder, F., Kinetic analysis of beta-phosphoglucomutase and its inhibition by magnesium fluoride. J Am Chem Soc 2009, 131 (4), 1575-88.
• Shim, J. U.; Olguin, L. F.; Whyte, G.; Scott, D.; Babtie, A.; Abell, C.; Huck, W. T.; Hollfelder, F., Simultaneous determination of gene expression and enzymatic activity in individual bacterial cells in microdroplet compartments. J Am Chem Soc 2009, 131 (42), 15251-6.