Helena Santos Lab
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Research at the Cell Physiology & NMR Lab is focused primarily on beneficial microorganisms that are sources of metabolites and enzymes with potential application in Biotechnology. Additionally, we study phospholipid biosynthesis in mycobacteria to identify novel anti-tuberculosis drug targets. |
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Helena Santos Phone (+351) 214469527
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Research Interests
Our research has two ultimate goals:
- understanding the principles that govern microbial physiology so that Metabolic Engineering strategies for the production of desirable end-products, e.g, biofuels, can be efficiently implemented;
- characterising the pathways for the synthesis of glycolipids derived from phosphatidylinositol to identify novel anti-tuberculosis drug targets.
This research group started in 1986, working in a topic that, at the time, was very challenging: NMR methods to study metabolism of living cells in a non-invasive way. It was this practice of examining whole cells, instead of breaking them, that led us to the current research line of Metabolic Engineering of Industrial Microorganisms. In parallel, since 1993, and for two decades, the team directed a great effort to understanding the molecular basis of thermophily in marine microorganisms able to grow at temperatures near 100°C. We focused on the role of low-molecular organic compounds in thermoprotection of cells and proteins; in particular, the biosynthesis of di-myo-inositol phosphate (DIP), a marker of adaptation to hot marine environments, was elucidated, and the respective biosynthetic enzymes fully characterized. Its biosynthesis involves CDP-inositol, a rare metabolite thus far restricted to the synthesis of DIP and of an inositol-phospholipid of the bacterium Rhodothermus marinus. Interestingly, the DIP synthase is an integral membrane protein despite the high polarity of reagents and products. Then, it became apparent that the synthesis of DIP evolved from the synthesis of phosphatidylinositol, the precursor of important virulence factors in the pathogenic bacterium Mycobacterium tuberculosis. This finding, along with the essentiality of phosphatidylinositol biosynthesis for growth of mycobacteria led us to the current effort to identifying efficient inhibitors of phosphatidylinositol synthesis as well as alternative promising targets for the development of novel anti-tuberculosis drugs.
Group Members
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Nuno Miguel Formiga Borges, Associate Research Scientist
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Maria José Leandro, Associate Research Scientist
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Pedro Miguel Lamosa, Associate Research
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Sara Rebelo, Research Technician
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Rodrigo Nobre, Research Fellow
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Alexandra Cabrita, Research Fellow
Subgroup on “Haemproteins”
David L. Turner, Invited Professor
Selected Publications
- A NEW PATHWAY FOR MANNITOL METABOLISM IN YEASTS SUGGESTS A LINK TO THE EVOLUTION OF ALCOHOLIC FERMENTATION C. Gonçalves, C. Ferreira, L. G. Gonçalves, D. L. Turner, M. J. Leandro, M. Salema-Oom, H. Santos & P. Gonçalves Frontiers in Microbiology 10, (2019); DOI: 10.339/fmicb.2019.02510.
- STRUCTURAL BASIS FOR PHOSPHOINOSITIDE BIOSYNTHESIS O. B. Clarke, D. Tomasek, C. D. Jorge, M. Kim, M. B. Dufrisne, S. Banerjee, K. R. Rajashankar, L. Shapiro, W. A. Hendrickson, H. Santos & F. Mancia Nature Communications, 6, 8505 (2015); DOI:10.1038/ncomms9505.
- A NOVEL PATHWAY FOR THE SYNTHESIS OF INOSITOL PHOSPHOLIPIDS USES CDP-INOSITOL AS DONOR OF THE POLAR HEAD GROUP C. Jorge, N. Borges & H. Santos Environmental Microbiology, (2014); doi: 10.1111/1462-2920.12734
Laboratory's Website
For further information please visit the laboratory's website
Fisiologia Celular e Ressonância Magnética (PT)
O nosso objectivo é esclarecer o conjunto de processos que permite que os microrganismos utilizem compostos orgânicos para sobreviverem, proliferarem e resistirem a stress ambiental, nomeadamente temperatura elevada, alta salinidade, ou valores de acidez elevados. O conhecimento da rede de processos que vai dos nutrientes aos produtos, permitirá manipular os microrganismos de modo racional e dirigido, e forçá-los a produzirem compostos com interesse prático. Estudámos principalmente bactérias usadas na indústria dos lacticínios e microrganismos que preferem temperaturas próximas de 100 graus. O conhecimento das estratégias que permitem a estas células proliferar em condições tão adversas permitir-nos-á obter agentes protectores de materiais biológicos, ou proteínas robustas que têm aplicação em processos industriais mais eficientes e amigos do ambiente. A técnica mais usada é a Ressonância Magnética Nuclear que permite estudar os processos metabólicos sem destruir as células, bem como caracterizar as moléculas novas que extraímos das células. Recentemente, foi iniciada uma nova linha de investigação que tem por objetivo último a identificação de novos alvos terapêuticos contra a tuberculose.
