Welcome to the homepage of the Machado Research Lab
Main research interests
Molecular Mechanisms of Exocytosis and EndocytosisNeurones and neuroendocrine cells release transmitters by Ca2+-dependent exocytosis from secretory vesicles. Two types of secretory vesicles are involved in exocytosis: synaptic vesicles, which store non-peptide neurotransmitters, and secretory granules or ‘large dense core vesicles’ (LDCV), which contain bioactive peptides, amines and other non-peptide neurotransmitters.
The phenomenon of exocytosis is a cellular process for releasing neurotransmitters, hormones, peptides and others local transmitters that occurs via fusion of secretory granules with the cell membrane, whereupon the granule content is at least partially released and the granule membrane is temporarily added to the plasma membrane. Exocytosis is balanced by compensatory endocytosis to achieve net equilibrium of the cell surface area and to recycle and redistribute components of the exocytosis machinery.
The main goal of the Machado Lab is to explore the molecular mechanisms that regulate the exocytosis, in particular which ones that are implicated in the accumulation of monoamines and peptides inside of the secretory granules and their release.
We use amperometry and Evanescent Field Microscopy to study exocytosis at the level of single vesicles. We also use molecular and biochemical techniques to address different steps of neurotransmitter release process.
The impact of this research lies in a better molecular, physiological and pharmacological understanding of the biogenesis and sorting of LDCVs, its transport to the plasma membrane, vesicle fusion, release of neurotransmitters across membranes, and messengers regulating different physiological processes.