|Name:||Margarida Maria Henriques Mesquita Bastos|
|Cargo||Data de Início|
|Member of the Scientific Committee Mestrado em Aplicações em Biotecnologia e Biologia Sintética||2021-09-20|
I started my scientific career as a PhD student in the field of Biocalorimetry, under the supervision of Prof. Ingemar Wadsö, at the Thermochemistry Group of Lund University, Sweden, that was considered the best in Europe by then. It was a promising scientific area both for its potentialities and for the fact that it did not exist in Portugal. On my return, I started to set up a Biocalorimetry research group, of which I am the scientific leader, at the Department of Chemistry and Biochemistry of the Faculty of Sciences of University of Porto, Portugal.
Later on I strengthened links with Portuguese Life Sciences experts, to provide me with both the samples and the biochemical/biological know-how that I lacked. I have always tried to get together people from different areas of knowledge and interests to solve common problems, which resulted over the years in a trans-national network that now encompasses biochemists, spectroscopists, computational biologists, peptide chemists and physicians, reflected on the variety of themes I have tackled and on the number of co-authors from different labs appearing in my publication list.
During my sabbatical in 1998 I went to the United States for half a year, as it was the leading country in biological calorimetry science and applications. During my stay in the US, I worked with Prof. Kenneth Murphy, Professor of Biocalorimetry, at the Department of Biochemistry of the University of Iowa, on a project devoted to the study of "Energetics of ovomucoid complexes with different proteases" and with Dr. Patrick Connelly, at that time the President Founder of the Althexis Company (a pharmaceutical SME) in Harvard, on "Thermodynamic studies of drug-receptor interactions". During the time in the US, I was invited by senior scientists Dr. Mike Gilson and Dr. Robert Goldberg to visit the NIST (National Institute of Standards and Technology), Washington, and to give there a lecture on my microcalorimetry research in Portugal.
In 2003 I introduced Neutron Scattering as an important tool for biophysical studies in my group, which is a whole new entry not only for us, but also within the Portuguese context, where it is still an under-explored field. Collaboration was started first with Dr. José Teixeira and Dr. Jean-Marc Zanotti, Laboratoire Léon Brillouin, Saclay, France. We recently published a paper on the study of the dynamics of an antimicrobial peptide at low hydration and low temperatures by neutron scattering and adiabatic low temperature calorimetry (experients performed by Prof Yuji Miyazaki and Prof Inaba at their lab in Osaka, Japan) addressing the old but still unanswered and relevant issue concerning the vibrational contribution to the heat capacity of proteins.
Finally in 2009 I started using a new biophysics tool in my studies on antimicrobial peptides/membranes, SAXD (Small Angle X-Ray Diffraction), which represented a pioneer work in Portugal. The work started in collaboration with Prof. Daniela Uhrikóva (Faculty of Pharmacy, J. A. Comenius University, Slovakia) and Dr. Sérgio S. Funari (HASYLAB, Desy, Hamburg, Germany). This technique is providing unique structural data on these systems that was not available through the techniques I used previously. We published a Letter in Biophysics Journal on the occurrence of a micellar cubic phase in he context of AMP/membrane systems and a paper in BBA (Biomembranes) on the structural diversity and mode of action of three lactoferrin antimicrobial peptides active against C. albicans, later another in Langmuir, 2018, where we propose the occurence of a Lγ phase induced in PE/PG memranes by the presence of the peptide, unsing a wide variety of biophyscal techniqes, including SAX and SANS. Finaly since 2017 we added the use of Molecular Dynamic simulations (MD) to address antimicrobial peptides interaaction with lipid model membranes, in a collabotaration with Dr. Rebeca Garcia-Fandino, Santiago de Compostela, Spain.
Particularly as regarding antimicrobial peptides and their interactions with model membranes, I started the research in this area in Portugal. In order to do it in a competitive and innovative way, I successfully launched efforts to bring together collaboration with scientists from different areas - Peptide Chemistry (Prof. Paula Gomes, University of Porto, Portugal and Prof. David Andreu, Barcelona, Spain), Fluorescence spectroscopy (Prof. Manuel Prieto, IST, Lisboa, Portugal), gathering Biophysics and Microbiology, through a collaboration with Prof. Salomé Gomes, IBMC, Porto, Portugal, a microbiologist specialized in avium and M. tuberculosis and a project with Prof Luis Rivas, CSIC, Madrid, on the interaction of AMP with Leishmania, FT Infrared Spectroscopy (Prof. Erik Goormaghtigh, Université Libre de Bruxelles, Belgium), Peptide Synthesis and Biological Activity Assays (Prof. Jan Bolscher, Free University of Amsterdam, The Netherlands), Neutron Scattering (Dr. Jean-Marc Zanotti, Laboratoire Léon Brillouin, Saclay, France and Dr. Dieter Middendorf, Clarendon Laboratory, UK), Low Temperature Heat Capacity Calorimetry (Dr. Yuji Myiazaki (Osaka University, Osaka, Japan) and Small Angle X-Ray Diffraction (Prof. Daniela Uhrikóva Faculty of Pharmacy, J. A. Comenius University, Slovakia) and Sérgio S. Funari (HASYLAB, Desy, Hamburg, Germany), ITC data treatment and interpretation for partition to lipid mambranes (Prof Sandro Keller, Kaiserlautern University, Germany, a specialist in ITC treatment of studies involving partition to membranes, that has proposed innovative approaches in this area), and in recently focusing on the interactions of antimicrobial D,L-α-Cyclic peptides (in collaboration with Prof.. Juan Granja, Santiago de Compostela, Spain) with bacterial model membranes by our biophysics techniques and also using MD, (in a collabotaration with Dr. Rebeca Garcia-Fandino, Santiago de Compostela, Spain).
Being always concerned about standardization and data reporting, she was co-leader of WG4 (Optimization of data quality ) of the COST action MOBIEU (Molecular Biophysics in Europe). There she lead together with Adrian Velasquez-Campoy (a renowned specialis in ITC, with emphasis in protein ligand binding studies) a benchmark ITC study where a wide comparispn is made between results for two test reactions, using different instruments and different data treatment programs. The study involved 5 Labs in Europe and 4 in USA, 18 ITC instruments and 4 data treatment programs. The results were published in 2021 in European Biophysics Journal, together with another paper poviding an SOP (standard Operation Procedure) for ITC measurements..