Miguel’s PhD research at the Vrije Universiteit of Amsterdam focused on synapses, the brain’s most characteristic feature that allows the flow of information encoding our cognitive functions, behavior, and memory.
Underlying Molecular mechanisms
Slight perturbations in synaptic function can derive in a wide range of psychiatric, neurodevelopmental, and neurodegenerative disorders. Miguel Gonzalez Lozano: “The aim of my PhD was to investigate the synaptic proteome and interactome in order to gain insights in the molecular mechanisms underlying synaptic function and dysfunction.” He continues: “To this end, I developed and applied multiple advanced mass spectrometry methodologies to study diverse aspects of the molecular composition of the brain, with special emphasis in the synapse and its dysfunction in disease.”
Dissecting machinery for protein delivery
For his Postdoc at Harvard Medical School, Gonzalez Lozano will dissect the machinery for protein delivery and processing of the Alzheimer-protein APP in human brain cells, using innovative technology. Accumulating evidences reveal the frequent association between neurodegenerative diseases and alterations in the endosomal sorting machinery, leading to misprocessing and accumulation of proteins like the Amyloid Precursor Protein (APP) in Alzheimer’s disease.
“In this project, I will bring together cutting-edge proteomics technologies and neuroscience to provide global understanding of the endosomal machinery and its role in the processing of APP.” Gonzalez Lozano continues: “Combining complementary large-scale approaches, I will systematically dissect the components of the sorting machinery to construct an interaction map of the endosomal proteome. I will reveal the precise APP processing products generated across endosomal compartments in human neurons and the impact of the sorting machinery on APP processing.”
This project will set the foundation for a complete and comprehensive framework to understand the endosomal system and APP processing mechanisms, which may be targeted therapeutically in the future.