Professor Mariarita Bertoldi

Biography

She received the PhD in Biochemistry in 1999 at the University of Verona (Italy) and since then, in the beginning of her scientific and academic career, her scientific interests were focused on protein chemistry and enzymology. Even if she worked on multiple research topics, including bovine pancreatic ribonuclease as a model for protein aggregation, or peroxiredoxin-2, as a novel essential redox enzyme for erythrocytes and central nervous system, her main scientific interest was focused on the chemistry of vitamin B6 dependent enzymes: aromatic amino acid decarboxylase (AADC), histidine decarboxylase, cystalysin, MalY. In this field, she gave important contributions to the understanding of the catalytic mechanism of these enzymes together with the unravelling of an unusual paracatalytic oxygen-consuming side reaction. For these studies, she won the Young Investigator Prize by Mc Graw-Hill and The Italian Biochemistry and Molecular Biology Society in 2002. Notably, the experience acquired on structure-to-function approach was fundamental for the development of her further research interests on variants of enzymes responsible for monoamine deficiencies.

In fact, since 2010, she has been dedicating her scientific efforts in elucidating the structural and functional impacts of pathogenic variants of AADC causing AADC deficiency. In details, she applied structural analyses at high resolution (X-ray crystallography) as well as bioinformatics (in silico site-directed mutagenesis together with molecular dynamics simulations) combined to low resolution in silico (coarse-grained molecular dynamics simulations) and in solution approaches (small angle X-ray diffraction and limited proteolysis) experimental approaches. Recombinant pathogenic variants have been further produced and analysed by a combination of biophysical and biochemical methods and some of them validated in the newly developed knockout neuronal AADC deficiency cell model. Altogether, the obtained results supported the importance of structural dynamics in governing the enzymatic activity of variants. This can pave the way to focused pharmacological approaches.

In addition, she gained important results concerning the determination of the impact of variants on the enzymatic function, with the aim to provide a contribution in predicting severity or mild disease presentation. This approach on AADC deficiency has been (or is going to be) applied to other monogenic neurotransmitter rare diseases: succinic semialdehyde dehydrogenase deficiency and tyrosine hydroxylase deficiency.

Her research activity is witnessed by several publications on international medium-high ranked journals. She has been granted by the University of Verona, by the Italian Ministry of Research and by several pharmaceutical companies. She has been invited as speaker in several international and national scientific meetings