Federico Forneris, 2013

Career Development Award Project Title

“Molecular Recognition at the Neuromuscular Synapse”, 2013

Who he is

Trained in physical chemistry and molecular biology, Federico Forneris returned to Italy after 5 years in the Netherlands at the beginning of 2014. Thanks to the Armenise Harvard Career Development Award, he now leads a laboratory of structural biology at the University of Pavia. In 2014 he also won the Levi Montalcini fellowship for young researchers.

What he does

The Forneris team studies the three-dimensional structures of molecules and their mechanisms of interaction and signalling. In particular, they are focused on the interactions between various ligands and receptors of the extracellular matrix, studying their role in the processes that lead to formation of large macromolecular complexes, with a strong focus on neuromuscular junctions: what enables communication between neurons in the brain and muscle cells, allowing us to move and breathe? The goal is to generate a “molecular blueprint” of the most critical interactions responsible for these processes: a little like trying to understand how an engine is made by looking at each of its essential components, to better understand how it actually works.

Forneris studies the processes of molecular recognition and regulation that are significant from the bio-medical viewpoint. The goal is to reveal the structures and mechanisms of tertiary and quaternary-induced activation in multi-domain proteins and multi-protein complexes that underlie these recognition and regulation processes. In the last thirty years, studies on the neuromuscular junctions have allowed identification of many of the protein molecules responsible for the formation of these particular synapses. Their malfunctions lead to a variety of diseases called myasthenic syndromes, including myasthenia gravis, which affects about 15-20 out of 100,000 people.

Certain proteins, essential for these processes, have only recently been identified, and as yet there is no detailed molecular characterization.

Thanks to these studies and by obtaining the three-dimensional structures of the molecules responsible for activation and regulation processes in the extracellular matrix, Forneris could envision a future where it will be possible to design specific molecules able to specifically target neuromuscular dysfunctions (including myasthenia gravis), with important consequences on the quality of life of patients.

News from the Lab 

The latest study, accepted for publication in The EMBO Journal, shows the three-dimensional structures of various human and viral complement regulators in complex with protein C3b and explores their functional features, providing a comprehensive validation to numerous biochemical investigations performed during the last 10-15 years about the specific functions of these molecules and their implications in multiple chronic and genetic diseases.