Angelini Lab | Biomolecular Engineering

Research approach

We apply directed evolution approaches to develop genetically encoded biomolecules with desired qualities from large combinatorial libraries. By using in vitro display technologies, such as phage and yeast surface display techniques, peptides and proteins of interest are evolved according to Darwinian principles including diversification, selection and amplification. Engineered properties include: binding affinity and specificity, molecular size, solubility and stability. Fine tuned biomolecules are further produced and characterized in vitro using a broad range of analytical methodologies. The efficacy of the engineered molecules is finally assessed ex vivo and in vivo. The ultimate goal of our research efforts is the development of state-of-the-art peptides and proteins with a novel mechanism of action that have the potential to overcome the limitations of current biomedical and biotechnological applications.

Research areas

Our research cover a broad range of techniques across multiple disciplines including molecular and structural biology, biochemistry and pharmacology. The team is currently interested in the following research areas:

multispecific proteins for cancer immunotherapy

Sito%20Web%20-%20Angelini%20Lab_12_edite

Cancer is a multifactorial disease that usually involves multiple ligands and receptors acting in concert. As a result, therapies targeting a single pathological molecule are often insufficient to achieve desired clinical outcomes. To overcome this limitation, we apply directed evolution approaches to engineer multispecific proteins capable of blocking multiple targets.

chemically modified peptides for the treatment of chronic inflammatory diseases

Cyclic peptides are able to bind a diverse set of target proteins and often display high stability and low off-target toxicity, making them an attractive molecule format for the development of next-generation therapeutics. We are currently applying directed evolution approaches to engineering novel post-translational chemically modified cyclic peptides for the treatment of chronic inflammatory diseases.

fundamental principles of molecular evolution

The data acquired through the directed evolution of peptides and proteins offer us the opportunity to answer questions about fundamental principles that govern molecular recognition. Toward this goal we are currently applying next-generation sequencing and complementary biochemical and biophysical techniques to dissect the evolutionary pathways and characterise the properties of the engineered biomolecules.

Collaborators

Prof. Christian Heinis - École polytechnique fédérale de Lausanne (Lausanne, Switzerland)
Prof. Laura Cendron - University of Padua (Padua, Italy)
Prof. Antonio Rosato - Istituto Oncologico Veneto and University of Padua (Padua, Italy)
Prof. Sarel-Jacob Fleishman - Weizmann Institute of Science (Rehovot, Israel)
Prof. Claudio Brancolini - University of Udine (Udine, Italy)
Prof. Gianfranco Pasut - University of Padua (Padua, Italy)
Prof. Patrizia Pontisso - University of Padua (Padua, Italy)
Prof. Gabriel Victora - Rockefeller University (New York, US)
Dr. Anna Toffan - Istituto Zooprofilattico Sperimentale delle Venezie (Padua, Italy)
Dr. Paola De Benedictis - Istituto Zooprofilattico Sperimentale delle Venezie (Padua, Italy)