info@epichembio.eu + 34 986 812 316

Enzymology group

mfsilva@fc.ul.pt
http://enzymology.fc.ul.pt/people/
Address
DQB, FCUL Edifício C8, Room. 8.4.55 Campo Grande 1749-016 Lisboa Portugal
Portugal
Keywords

Metabolome, proteome, drug target, metabolic pathways, structural biology

Models

Leishmania infantum, Vitis vinifera, yeast (S. cerevisiae), bacteria (E. coli)

Techniques

• Proteomics: FT-ICR mass spectrometry (ESI and MALDI), Peptide Mass Fingerprint, Post-translational modifications (glycation, nitrosylation) • Metabolomics: untargeted metabolomics; FT-ICR-MS using direct infusion and analysis by ESI+ and ESI-; nanoLC- and capLC-MS • Enzymology and Pathway analysis: enzyme activity assays (initial rate and time-course analysis), Modelling and computer simulation of metabolic networks, recombinant protein expression and purification

Collaborations outside COST

We are a research group dedicated to unravel enzyme function and structure, exploring the exquisite complexity of life through a systems biology approach, mainly focused in amyloid disorders and infectious diseases. Our final goal is to shape the rules of life to our defined purposes such as changing enzyme specificity, rewiring pathways and creating novel functional macromolecular structures. In the MS and proteomics field, we collaborate with several research groups, namely Neil Kelleher’s at Northwestern University, Peter Roepstorff’s at Southern Denmark University, Roman Zubarev’s at Karolinska Institute, and Albert Heck’s at Bijvoet Center. We also collaborate with clinicians from Hospital de Curry Cabral (Lisbon) in the area of amyloid diseases. In the quest for new therapeutic targets and development of new drugs against human diseases (amyloid and infectious) we interact with organic chemists from Lisbon University.

Short description of ongoing research projects

Current research focuses on mass spectrometry-based metabolomics and proteomics, and its application in biomarker discovery and drug development. Using ultra-high resolution and high-mass accuracy provided by FT-ICR-MS, metabolite and protein analysis is being performed in two different models of highly relevant infectious diseases: Human visceral leishmaniasis (an important public health problem) and grapevine downy-mildew (a major economical concern). Based on the identified metabolites and enzymes, a network of significant metabolic pathways will be built, revealing the pathways and the mechanisms underlying infection and key metabolites associated with resistance and survival.

Publications
  1. Sousa Silva M, Gomes RA, Ferreira AEN, Ponces Freire A, Cordeiro C (2013) The glyoxalase pathway: The first hundred years… and beyond. Biochem J 453(1): 1-15
  2. Lages NF, Cordeiro C, Sousa Silva M, Ponces Freire A, Ferreira AEN (2012) Optimization of time-course experiments for kinetic model discrimination. PLoS One 7(3): e32749
  3. Gomes RA, Franco C, Da Costa G, Planchon S, Renaut J, Pinto F, Sousa Silva M, Coelho AV, Ponces Freire A, Cordeiro C (2012) The proteome response to amyloid protein expression in vivo. PLoS One 7(11): e50123
  4. Fortes AM, Agudelo-Romero P, Silva MS, Ali K, Sousa L, Maltese F, Choi YH, Grimplet J, Martinez-Zapater JM, Verpoorte R, Pais MS (2011) Transcript and metabolite analysis in Trincadeira cultivar reveals novel information regarding the dynamics of grape ripening. BMC Plant Biology 11: 149. DOI: 10.1186/1471-2229-11-149
  5. Sousa Silva M, Barata L, Ferreira AEN, Romão S, Tomás AM, Ponces Freire A, Cordeiro C (2008) Catalysis and molecular properties of Leishmania infantum glyoxalase II: trypanothione specificity and the evolution of trypanosomatids. Biochemistry 47(1): 195-204
Other activities of potential interest to others

- Member of the Action Group A3 on “Prevention of functional decline and frailty” of the European Innovation Partnership on Active and Healthy Ageing (EIP-AHA, European Commission), and co-representative of the FCUL Consortium in this Action Group. - Member of the Steering Committee of the Portuguese Mass Spectrometry Network (RNEM).


Cost UE