Computational Biologist & Protein Designer
Postdoctoral Research Fellow, University of Nova Gorica

I am a Computational Biologist with extensive wet-lab expertise, working for over 8 years in the characterization of novel proteins/enzymes and studying structure-function interconnections during evolution. I specialize in integrating wet-lab and computational methods.

Currently, I am focusing on Protein Design, developing custom workflows that integrate AI- and physics-based methods to generate binders for folded and unfolded epitopes of medically relevant biomarkers.

I want to drive innovation in protein and biocatalyst discovery, evolution, and engineering for industrial and biomedical applications.

In my view, the future of biotech relies on self-improving AI approaches (Transfer Learning, RL) supervised on data to autonomously build models, hypotheses, and experiments. I aim to contribute to this future of supervised automation.

Project Overview: Developing an AI-driven pipeline to target challenging, poorly immunogenic biomarkers like CDKL5. We integrate Machine Learning to design and re-design protein binders against folded and unfolded epitopes, optimizing for developability to distinguish isoforms. A key focus is achieving success with minimal experimental screening (<15 characterized designs), leveraging computational precision to bypass high-throughput bottlenecks.

• An integrative structural biology approach to identify the binding mode of a nanobody towards the pea ascorbate peroxidase Authors: C D’Ercole, M Orlando, KE Filipič, A De Marco Venue: Computational and Structural Biotechnology Journal

• A crucial active site network of titratable residues guides catalysis and NAD+ binding in human succinic semialdehyde dehydrogenase Authors: S Cesaro, M Orlando, I Bettin, C Longo, G Spagnoli, PP de Laureto, ... Venue: Protein Science 34 (1), e70024

• Biochemical and cellular studies of three human 3‐phosphoglycerate dehydrogenase variants responsible for pathological reduced L‐serine levels Authors: G Murtas, E Zerbini, V Rabattoni, Z Motta, L Caldinelli, M Orlando, ... Venue: Biofactors 50 (1), 181-200

• On the quaternary structure of human D‐3‐phosphoglycerate dehydrogenase Authors: D Riva, M Orlando, V Rabattoni, L Pollegioni Venue: Protein Science 33 (8), e5089

• The co‐existence of cold activity and thermal stability in an Antarctic GH42 β‐galactosidase relies on its hexameric quaternary arrangement Authors: M Mangiagalli, M Lapi, S Maione, M Orlando, S Brocca, A Pesce, ... Venue: The FEBS Journal 288 (2), 546-565

• An anti-HER2 nanobody binds to its antigen HER2 via two independent paratopes Authors: D Ubbiali, M Orlando, M Kovačič, C Iacobucci, MS Semrau, G Bajc, ... Venue: International journal of biological macromolecules 182, 502-511

• CDR1 composition can affect nanobody recombinant expression yields Authors: M Orlando, S Fortuna, S Oloketuyi, G Bajc, A Goldenzweig, A De Marco Venue: Biomolecules 11 (9), 1362

• Valorization of organic waste through black soldier fly: On the way of a real circular bioeconomy process Authors: D Bruno, M Orlando, E Testa, MC Miino, G Pesaro, M Miceli, L Pollegioni, ... Venue: Waste Management 191, 123-134

• Electroconductive bionanocomposites from black soldier fly proteins for green flexible electronics Authors: E Testa, V Barbera, E Fasoli, U Giese, MR Belviso, P Rossini, D Bruno, ... Venue: ACS Sustainable Chemistry & Engineering 13 (6), 2388-2400

• Plastic-degrading microbial consortia from a wastewater treatment plant Authors: A Salini, L Zuliani, PM Gonnelli, M Orlando, A Odoardo, D Ragno, ... Venue: International Journal of Molecular Sciences 25 (23), 12747

• Microbial enzyme biotechnology to reach plastic waste circularity: current status, problems and perspectives Authors: M Orlando, G Molla, P Castellani, V Pirillo, V Torretta, N Ferronato Venue: International Journal of Molecular Sciences 24 (4), 3877

• Efficient polyethylene terephthalate degradation at moderate temperature: a protein engineering study of LC‐cutinase highlights the key role of residue 243 Authors: V Pirillo, M Orlando, C Battaglia, L Pollegioni, G Molla Venue: The FEBS journal 290 (12), 3185-3202

• An efficient protein evolution workflow for the improvement of bacterial PET hydrolyzing enzymes Authors: V Pirillo, M Orlando, D Tessaro, L Pollegioni, G Molla Venue: International Journal of Molecular Sciences 23 (1), 264

• Polysaccharide degradation in an Antarctic bacterium: Discovery of glycoside hydrolases from remote regions of the sequence space Authors: M Orlando, A Marchetti, L Bombardi, M Lotti, S Fusco, M Mangiagalli Venue: International Journal of Biological Macromolecules 299, 140113

• Xylan Degradation in the Halotolerant Bacterium Bacillus altitudinis relies on glycosidic hydrolases from families 11 and 30 Authors: A Marchetti, M Orlando, S Digiovanni, C Christakis, V Tsopanakis, ... Venue: Journal of Agricultural and Food Chemistry 73 (43), 27599-27610

• Evolutionary history and activity towards oligosaccharides and polysaccharides of GH3 glycosidases from an Antarctic marine bacterium Authors: A Marchetti, M Orlando, L Bombardi, S Fusco, M Mangiagalli, M Lotti Venue: International Journal of Biological Macromolecules 275, 133449

• Thermophilic hemicellulases secreted by microbial consortia selected from an anaerobic digester Authors: L Bombardi, M Orlando, M Aulitto, S Fusco Venue: International Journal of Molecular Sciences 25 (18), 9887

• A cold‐active esterase enhances mesophilic properties through Mn2+ binding Authors: A Marchetti, M Orlando, M Mangiagalli, M Lotti Venue: The FEBS Journal 290 (9), 2394-2411

• Mn2+ binding affects the thermal properties of an Antarctic esterase Authors: A Marchetti, M Orlando, M Mangiagalli, M Lotti

• The GH19 Engineering Database: Sequence diversity, substrate scope, and evolution in glycoside hydrolase family 19 Authors: M Orlando, PCF Buchholz, M Lotti, J Pleiss Venue: PLoS One 16 (10), e0256817

• The “cold revolution”. Present and future applications of cold-active enzymes and ice-binding proteins Authors: M Mangiagalli, S Brocca, M Orlando, M Lotti Venue: New biotechnology 55, 5-11

• Endolysins from Antarctic Pseudomonas Display Lysozyme Activity at Low Temperature Authors: M Orlando, S Pucciarelli, M Lotti Venue: Marine drugs 18 (11), 579

• Biochemical and biophysical analysis of two Antarctic lysozyme endolysins and in silico exploration of glycoside hydrolase 19 sequence space Authors: M Orlando Venue: Università degli Studi di Milano-Bicocca

• Towards elucidating species diversity of European inland Strigamia (Chilopoda: Geophilomorpha): a first reassessment integrating multiple lines of evidence Authors: L Bonato, F Bortolin, G De Zen, P Decker, EN Lindner, M Orlando, ... Venue: Zoological Journal of the Linnean Society 199 (4), 945-966

• New insights into Plutonium, one of the largest and least known European centipedes (Chilopoda): distribution, evolution and morphology Authors: L Bonato, M Orlando, M Zapparoli, G Fusco, F Bortolin Venue: Zoological Journal of the Linnean Society 180 (4), 887-909 (2017)

• Evolution of Strigamia centipedes (Chilopoda): a first molecular assessment of phylogeny and divergence times Authors: L Bonato, F Bortolin, L Drago, M Orlando, L Danyi Venue: Zoologica Scripta 46 (4), 486-495 (2017)

Happy to get in contact for scientific collaborations, seminars and any opportunity you may want to share in the protein evolution, discovery and design field :)

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