Biosketch

Prof. dr. Giovanni Maglia

Giovanni Maglia studied chemistry at the University of Bologna, Italy received his PhD in chemical biology at the University of Birmingham (2004), UK and continued his studies in biophysics at the Universities of Leuven, BE and Oxford, UK. The main focus of Giovanni’s research group is on the characterization and engineering of biological nanopore sensors. In particular, they use the available tools in chemistry to engineer, modify and redesign protein nanopores for applications in nanobiotechnology, molecular sensing, synthetic biology and single-molecule biophysics. Giovanni developed a particular interested in applying academic research towards practical application. He was an early contributor to develop a DNA sequencing technology that is now being commercialized by Oxford Nanopore technologies. More recently, his laboratory has been focusing on proteins. His first showed that nanopore can be used to study folded proteins, with applications in single-molecule enzymology and real-time metabolomic analysis. His research group also showed that nanopores can be engineered to identify peptides in order to develop a nanopore spectrometry device for protein identification. Throughout his career, he focused on the bioengineering of complex nanopore-device assemblies with higher level functions, that are used for the characterisation, manipulation and control of single proteins. At present, his group is focussing on the sequencing of full-length proteins.

Three top publications 2017-2022

1. Galenkamp N, Biesemans A & Maglia G (2020) Directional conformer exchange in dihydrofolate reductase revealed by single-molecule nanopore recordings. Nature Chemistry 12(5):481-488; DOI: https://doi.org/10.1038/s41557-020-0437-0

This work showed a remarkable example of single-molecule enzymology using nanopores. It was found that proteins can be electrophoretically trapped inside a nanopore and tiny conformational changes measured by ionic currents. Single-molecule investigations revealed that the enzyme dihydrofolate reductase folds in more than one structure. Like in a two-stroke engine, the free-energy of the chemical step and cofactor binding was used to switch between the two folded structures. It was proposed that this mechanism is used by the enzyme to improve the efficiency of catalysis in high concentrations of oxidized cofactors.

2. Lucas FLR, Versloot RCA, Yakovlieva L, Walvoort TCM & Maglia M (2021) Protein identification by nanopore peptide profiling. Nature Communications 12: 5795; DOI: https://doi.org/10.1038/s41467-021-26046-9

In this work, Giovanni Maglia’s group showed that biological nanopores can be used to study a variety of peptides. In turn, proteins digested into peptides by a protease could be recognized by comparing the resulting ionic current spectra. This approach might allow using biological nanopores in low-cost devices for the analysis and sequencing of proteins at the single-molecule level.

3. Zhang S, Huang G, Versloot RCA, Bruininks BMH, de Souza PCT, Marrinks SJ & Maglia G (2021) Bottom-up fabrication of a proteasome–nanopore that unravels and processes single proteins. Nature Chemistry 13(12): 1192-1199; DOI: https://doi.org/10.1038/s41557-021-00824-w

In this work a biological nanopore was designed from the bottom up from three different proteins. A Bacterial transmembrane pore was fused a Eukaryotic regulatory protein. The latter was then fused to an Archaeal proteasome. The resulting supramolecular complex formed a biological nanopore that allowed the capture, unfolding and processing of single proteins across biological nanopores. This example will allow the analysis and potentially sequencing of proteins at the single-molecule level.