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Cell Physiology & NMR

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Research at the Cell Physiology & NMR Lab is focused on beneficial microbes, i.e., microorganisms that promote human health or well-being, or are sources of new metabolites and enzymes with potential application in biotechnology..

 

Helena Santos
Professor Catedrático
PhD 1984 in Biophysics, Universidade Nova de Lisboa

Phone (+351) 214469541 | Extension 1541
santos@itqb.unl.pt

 

Research Interests

Our research has two ultimate goals:

  • understanding the molecular basis of adaptation to thermophily in marine microorganisms adapted to grow at temperatures near 100°C;
  • understanding the principles that govern cell biology so that Metabolic Engineering strategies for the production of desirable end-products can be efficiently implemented (Systems Metabolic Engineering).

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 two research lines that are active today: the role of low-molecular organic compounds in the thermoprotection of cellular components of microbes adapted to hot environments, and Metabolic Engineering of industrial bacteria.

Hyper/thermophiles isolated from seawater sources accumulate organic solutes (thermolytes) not only . In response to an increase in salinity, but also in response to heat stress. These solutes are different from those used by mesophilic microorganisms for osmoadaptation. Our team characterised a number of thermolytes and demonstrated their superior efficacy on the stabilization of different biomaterials such as proteins. Therefore, we gathered evidence supporting a link between solute accumulation by (hyper)thermophiles and structural protection against heat damage. We continue our effort to screen for novel thermolytes and to answer the following questions: What novel pathways and enzymes are used in the synthesis of thermolytes? What is the total molecular and regulatory network, from sensing the stress to synthesising the solute? What are the molecular mechanisms underlying protein protection by thermolytes? Are they effective in the cell milieu? We believe that the answers will allow for the design of useful tailor-made stabilizers and to new knowledge on the physiology supporting Life at high temperature.

In another line, we use in vivo NMR coupled with 13C-labelling to measure on line the dynamics of intracellular metabolites to provide useful guidelines for metabolic engineering strategies. The team collaborates with USA and EU groups with expertise in mathematical modelling for the integration of the data at multi-level organization. Target organisms: Lactococcus lactis for the production of nutraceuticals and Corynebacterium glutamicum for the production of reagents for the chemical industry from renewable resources.

 

Group Members

    • Nuno Miguel Borges, Auxiliary Investigator
    • Pedro Miguel Lamosa (25%), Auxiliary Investigator and Manager of CERMAX
    • Luís Gafeira Gonçalves, Post-Doc
    • Carla Alexandra Jorge, Post-Doc (Cosupervisor: Júlia Costa)
    • Marta Viseu Rodrigues, Post-Doc (Cosupervisor: C. Arraiano)
    • Gonçalo Graça, Post-Doc
    • Dušica Radoš, PhD Student (Cosupervisor:B. Eikmanns & A. R. Neves)
    • Ana Maria Esteves, PhD Student (Cosupervisor: N. Borges)
    • Cristiana Faria, PhD Student (Cosupervisor: I. Rocha e N. Borges)
    • Inês Torcato, Research Student
    • Dário Neves, Research Student
    • Joana Sousa, Master Student
    • Sara Rebelo, Technical Assistant

Subgroup on “Haemproteins”

    • David L. Turner, Invited Professor
    • Teresa Catarino, Assistant Professor
    • Andreia Cepeda, Research Student

 

Selected Publications

  1. MANNOSYLGLYCERATE STABILIZES STAPHYLOCOCCAL NUCLEASE WITH RESTRICTION OF SLOW β-SHEET MOTIONS T. M. Pais, P. Lamosa, M. Matzapetakis, D. L. Turner & H. Santos. Protein Science, 21, 1126-1137 (2012).
  2. EVOLUTION OF THE BIOSYNTHESIS OF DI-MYO-INOSITOL PHOSPHATE, A MARKER OF ADAPTATION TO HOT MARINE ENVIRONMENTS L. G. Gonçalves, N. Borges, F. Serra, P. L. Fernandes, H. Dopazo & H. Santos Environmental Microbiology, 14, 691-701 (2012).
  3. HIGH YIELDS OF 2,3 BUTANEDIOL AND MANNITOL IN Lactococcus lactis THROUGH ENGINEERING NAD+ COFACTOR RECYCLING P. Gaspar, A. R. Neves, M. J. Gasson, C. A. Shearman & H. Santos Applied and Environmental Microbiology, 77, 6826-6835 (2011). 

 

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, permitir-nos-á manipular os microrganismos de modo racional e dirigido, e forçá-los a produzirem compostos com interesse prático. Estudamos 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.

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