Our research at ULisboa aims to decipher molecular mechanisms underlying protein misfolding and aggregation in human disease, with a focus on amyloid formation in neurodegenerative diseases.
We investigate novel anti-aggregation chaperones in Alzheimer's Disease and how metal ions in the brain influence amyloid formation.
We also research on protein misfolding in mitochondrial metabolic and neurological diseases.
We combine molecular, cellular and biochemical experimental approaches to investigate protein structure and self-assembly in vitro and in cells.
Implemented techniques comprise:
● Purification of disease causing proteins (Aβ, Tau, Syn)
● Mechanistic analysis of amyloid aggregation kinetics;
● Structural biophysics analysis (CD, ATR-FTIR fluorescence)
● Enzymatic assays (ETC, β-oxidation)
● cell toxicity and RT-QuIC assays.
The laboratory is a vibrant workplace composed by passionate and curious team members from different backgrounds, nationalities and training levels.
Team effort is driven by high-quality, thorough research in protein biochemistry and biophysics.
We regularly welcome visiting professors in sabbatical periods and international students in short term research internships.
Through collaboration we summon knowledge, methodological resources and training opportunities for team members that allow tackling our research questions in a multidisciplinary perspective, from molecules, to cells to organisms.
Our collaborative network includes +10 research institutions worldwide and includes physicists, computational biologists, mathematicians, cell biologists and clinicians.
Understanding the mechanistic aspects of protein self-assembly and amyloid formation is critical to establish cellular and molecular modulators of protein aggregation in the diseased brain.
Through kinetics and mechanistic analysis, we are investigating amyloid formation by Aβ, Tau and Syn.
We seek to establish how cellular conditions, small molecules and antibodies influence protein aggregation, to assist in defining better therapies.
S100 proteins in Alzheimer’s Disease
S100 proteins are recognized biomarkers for brain distress in neurodegenerative conditions including Alzheimer’s.
We seek to uncover novel molecular mechanisms implicating S100 proteins, that link aggregation and neuroinflammation cascades.
We recently uncovered novel neuro-protective functions which imply S100 alarmins in vital house-keeping processes that harness AD.
Specifically, we found that under physiological conditions mimicking early disease states, S100B acts as a new type of molecular chaperone delaying aggregation.
This is achieved through binding of monomeric Aβ to S100B.
Brain metal ions and protein aggregation
In neurodegeneration, imbalance in metal ion homeostasis results in altered homeostasis with deleterious consequences.
On the one hand, we are investigating how metal-protein interactions influence protein aggregation and the oligomers landscape.