FTICR-MS and Structural Mass Spectrometry

FTICR-MS (Fourier Transform Ion Cyclotron Resonance Mass Spectrometry) provides high resolution, high mass accuracy, and the ability to manipulate ions in the gas-phase as well as multiple fragmentation methods. We deploy FTICR-MS as an analytical tool in proteomics and metabolomics. We are also interested in protein-ligand interactions and top-down proteomics. Thanks to a substantial grant from FCT we will be developing native MS for protein structure analysis.

Protein Folding, Glycation and Neurodegenerative Diseases

Methylglyoxal and other 2-oxoaldehydes are non-enzymatic by-products of metabolism in eukaryotic cells. 2-Oxoaldehydes form advanced glycation end-products (AGEs) in proteins, impairing the biochemical functionality of these essential macromolecules.

The main goals are to understand the effects of glycation on protein structure and stability, using model proteins and recombinant proteins involved in familial amyloidotic polyneuropathy (transthyretin) and Parkinson’s disease (α-synuclein).

Novel Therapeutic Targets in Trypanosomatids

All trypanosomatids present two characteristics that set them apart from all other eucaryotic cells: glycolysis compartmentalization and the functional replacement of glutathione by trypanothione (N1,N8- Bis-glutathyonylspermidine).

The glyoxalase pathway and nitric oxide signalling are being investigated in Leishmania infantum as potential as a therapeutic targets.

Modelling and Computational Analysis of Biochemical Systems

Current biochemical research is focused on the study of entire pathways and of living systems as a whole.

This systems biology approach brings a different perspective for research performed in the lab and presents new challenges for data analysis tools. The main goals are the application of mathematical and computational concepts to the characterization of metabolic operating states and identification of regulation patterns.

Parameter estimation is one of the limiting step for modelling and simulation of biochemical systems. The other is model discrimination, the procedure of deciding what model is the best among a set of candidates. Computational methods for this purpose are implemented using Evolutionary Algorithms (visit the page about the software developed in our group).