An AFM facility

  Biomembranes - Research
Aims | People | Research | Methodologies | Publications & Patents |
Extra Activities | Opportunities |

The Biomembranes Unit is mainly focused on the biochemical and biophysical processes occurring at membrane level of human cells, as well as of their viral and bacterial pathogens.


We have been working on the stud
y of the two steps of the life cycle of enveloped viruses (mainly HIV-1 and dengue virus) that involve biomembranes: the entrance of the virus or its content into the target cell and the assembly of new virions. Our studies have clarified the mechanism of action at the molecular level of some HIV entry inhibitors and pointed out strategies to improve their efficacy. Regarding dengue virus (DENV), our recent studies demonstrated that the DENV capsid (C) protein binds to proteins on the surface of intracellular lipid droplets (LD), majorly perilipin 3 (TIP47). This interaction, essential to viral replication, depends on the high intracellular potassium concentration, and may regulate the availability of the C protein, allowing its proper participation on the virus replication cycle. We have also showed that a peptide designed based on a conserved segment within the disordered N-terminal region of DENV C region is able to inhibit the DENV C – LD binding. These advances pave the way to drug development approaches, in which inhibitory efficiency may be improved through lead optimization.


We have also been studying the binding of fibrinogen to the erythrocyte membrane and its relevance as a significant cardiovascular risk factor. At this level, we have identified a previously unknown receptor for fibrinogen on the erythrocyte membrane, which is altered in some human pathologies. Furthermore, we identified strategies to inhibit its contribution to the erythrocyte hyperaggregation associated with high plasma fibrinogen levels.


The Biomembranes Unit is also involved on the pre-clinical evaluation of the membrane activity and mechanism of action at the molecular level of antimicrobial peptides (AMP) and cell-penetrating peptides (CPP), most of them based on naturally occurring amino acid sequences.


On the Nanotechnology/Nanomedicine area, we are also working on the development of innovative biosensor systems, with improved selectivity and sensitivity (e.g., nanoparticles and amyloid-based biosensors).
Based on the results obtained so far, the work to be developed by the Biomembranes Unit on the near future may contribute for the identification of new drug targets, therapeutic strategies and/or diagnostic methods for important human pathologies, such as cardiovascular diseases, HIV/AIDS and dengue.

 

 graphical_abstract_NSantos_lab

 Graphical abstracts of the main research activities

 

Research Projects

2015/2020, Engineering protease-resistant alpha-beta peptides for broad-spectrum antivirals.
National Institute Of Allergy And Infectious Diseases, National Institutes of Health (NIH), USA. Award Number: R01AI114736
Portuguese PI: N. C. Santos​
 
2013/2018, The Role of Fibrin Clot Structure in Thrombosis.
British Heart Foundation.
Participant PI: N.C. Santos.
 
2014/2017, DELIN: An innovative approach to deliver dual targeting HIV entry inhibitors using cationic liposomes.
FCT/ HIVERA (European Union).
Participant PI: N.C. Santos.
 
2014/2016, Multi-target HIV entry inhibitors delivery by cationic liposomes.
FCT, FCT - VIH/SAU/0047/2011.
Participant PI: N.C. Santos.
 
2010/2016, The interplay between lipid droplets, RNA and the capsid protein during dengue virus assembly and encapsidation.
FCG, Calouste Gulbenkian Foundation Frontiers in Life Sciences Research Prize.
Coordinator: I.C. Martins.
 
2012/2014, Do IT - Desenvolvimento e Operacionalização da Investigação de Translação.
Quadro de Referência Estratégico Nacional (QREN).
Participant PI: N.C. Santos.
 
2011/2014, LIPIDENGUE: The role of hepatic lipid membranes and lipid droplets in Dengue virus encapsidation. A gateway to new therapies.
FCT, FCT - PTDC/QUI-BIQ/112929/2009
Coordinator: M. Castanho.
 
2010/2014, MEMPEPACROSS: Membrane-active peptides across disciplines and continents: An integrated approach to find new strategies to fight bacteria, dengue virus and neurodegeneration.
Marie Curie FP7 European Union People Programme, Programme “People” – Marie Curie International Research Staff Exchange Scheme – Call identifier: FP7-PEOPLE-2009-IRSES.
Coordinator: N.C. Santos
 
2010/2014, Atomic force microscopy-based molecular recognition of fibrinogen receptors in platelets and erythrocytes.
Applications in health and disease.
FCG, Calouste Gulbenkian Foundation Prize Stimulus to Research.
Coordinator: N.C. Santos.
 
2010/2014, Membrane fusion mechanism of Influenza Hemagglutinin: a simulation and biophysical approach.
FCT, FCT - PTDC/QUI-BIQ/114774/2009.
Participant PI: N.C. Santos.
 
 

International Collaborations

  • Andrea Da Poian (Federal University of Rio de Janeiro, Brazil)
  • Anne Moscona (Cornell University, New York, USA)
  • Antonello Pessi (PeptiPharma, Rome, Italy)
  • Benhur Lee (Mount Sinai School of Medicine, New York, USA)
  • Charlotte A.E. Hauser (Institute of Bioengineering and Nanotechnology, Singapore)
  • David Andreu (Pompeu Fabra University, Barcelona, Spain)
  • Eleonora Kurtenbach (Federal University of Rio de Janeiro, Brazil)
  • Fábio C.L. Almeida (Federal University of Rio de Janeiro, Brazil)
  • Gregory Melikian (Emory University, Atlanta, USA)
  • Marcel Tabak (University of Sao Paulo, Sao Carlos, Brazil)
  • Matteo Porotto (Cornell University, New York, USA)
  • Octavio Franco (Catholic University of Brasilia, Brazil)
  • Peter J. Bond (Bioinformatics Institute, Singapore)
  • Robert Ariens (University of Leeds, UK)
  • Sebastian Maurer-Stroh (Bioinformatics Institute, Singapore)

 

Prizes

  • 2014 Best Talk - Young Investigator Travel Award, XXIIIrd International Fibrinogen Workshop, Marseille, France (Ana Filipa Guedes)
  • 2013 Best Poster Award at the EBSA 2013, Lisbon, Portugal (André Faustino).
  • 2010 Research Programme in Frontiers of Life Sciences from Calouste Gulbenkian Foundation (Ivo Martins).
  • 2009 Gulbenkian Prize to Stimulus for Research 2009 (Marco M. Domingues).
  • 2005 José Luís Champalimaud Prize on HIV Research (Applied Research and Technologies area).
  • 2004 José Luís Champalimaud Prize on HIV Research (Basic Research area).
  • 2001 Calouste Gulbenkian Foundation Prize (for researchers under 31).


 

Av. Professor Egas Moniz
Edifício Egas Moniz,
1649-028 Lisboa
Portugal
 

Tel: (+351)217985136
Fax: (+351)217999477


Financiado por: