Newsletter March 2017

In memory of René Thomas (14/05/1928 – 09/01/2017)

By Em. Prof. Dr. Max Mergeay , Belgian Nuclear Research Center (SCK•CEN)

René Thomas was born on May 14th, 1928, in Brussels, Belgium. His parents were the poet Lucien-Paul Thomas and Marieke Vandenbergh.  After he earned his high school diploma from the Athénée Royal d’ Ixelles (Brussels), he studied chemistry at the Université Libre de Bruxelles (ULB). There, he attended Jean Brachet‘s  lectures. Under the supervision of this pioneer in the field of nucleic acids and their function in heredity and protein synthesis, R. Thomas prepared a thesis on the denaturation of DNA, which he defended in 1954. His outstanding scientific carrier is attested by a number of awards, including the Francqui prize in 1975, the Prix Quinquennal from the Fonds National de la Recherche Scientifique in 1985 (for his discoveries on DNA, gene transfer in  bacteria and genetic regulation) and the Golden Medal from the Institut de France in 1999. He was elected as a member of the Royal Academy of Sciences of Belgium in 1986.

Numerous past and present BSM members have been his students and feel deeply privileged to have enjoyed his teaching, his scientific rigour, openness, clever mind, warm friendship and deep rooted humanism.

The research work of R. Thomas was conducted at ULB, where he was Professor of Genetics. It covered a wide range of topics, all of them united by the conviction that it will not be possible to understand complex systems without understanding the logic of simpler systems.

Main scientific discoveries

  1. DNA denaturation
  2. Positive control of gene expression (using the model E.coli phage, Lambda).
  3. Logical description, analysis and synthesis of complex networks via Boolean algebra.
  4. Crucial role of positive and negative regulations in the dynamics of biological systems.
  5. From the logical viewpoint back to the differential equations viewpoint: the study of deterministic chaos and symmetric attractors.

From biochemistry to phage genetics, and later to mathematical biology and dynamical systems, R. Thomas addressed more and more complex theoretical questions, moving from wet experiments to computational simulations, always with the same experimental mind frame. His contributions were and still are authoritative, in particular in the recent context of systems biology.

Thanks to Ariane Toussaint for providing the information about Prof. em. René Thomas.

Subterranean Pharmacy:

Diversity, Ecology and Therapeutical Potential of Antibiotic Makers of Cave Moonmilk Deposits

By Dr. Sébastien Rigali, InBios – Center for Protein Engineering, Liège University (ULg)

Streptomyces and other filamentous Actinobacteria offered us most of bioactive compounds currently used in human therapy (antibacterial, antifungal, and anticancer agents… amongst many others). As bacterial resistance to antibiotics is on the rise and a return to the ‘pre-antibiotic’ era has become a frightening possible scenario, there is a renewed interest at isolating novel Actinobacteria from extreme and still poorly investigated environments. Bioprospecting the ‘extremobiosphere’, including the subterranean ecosystems such as caves, revealed a great abundance and diversity of members of the phylum Actinobacteria, raising a series of questions about their adaptations and ecological functions in these inorganic and highly oligotrophic habitats, and at the same time, providing great hope for the identification of novel compounds with therapeutical properties. Secondary cave carbonate deposits known as moonmilk, have been reported to host rich and diverse microbial populations, including Actinobacteria, which are believed to participate in their genesis via constructive (precipitation) and destructive (dissolution) calcium carbonate (CaCO3) processes. Interestingly, ancient medical texts also reported that moonmilk had therapeutical properties, thereby suggesting that its filamentous endemic actinobacterial population might be a source of natural products useful against human infection disease.

With this purpose in mind, the ‘Strepto’ group at the University of Liège undertook a screening approach in order to isolate cultivable Actinobacteria from moonmilk of the “Grotte des Collemboles” located in Comblain-au-Pont in Belgium (Figure 1A). Marta Maciejewska (Figure 1B), who is defending her thesis on March 31st 2017, evaluated the taxonomic profile of moonmilk-dwelling Actinobacteria (Figure 1C), and assessed their putative role in the genesis of this carbonate deposits and their potential in biosynthesis of antimicrobials. Genome mining and in vitro assays suggested that cave-dwelling bacteria could participate to CaCO3 precipitation by a wide spectrum of biomineralization processes supporting the hypothesis that filamentous Actinobacteria could indeed be key protagonists in moonmilk genesis. Phylogenetic analysis revealed that all moonmilk culturable isolates (Figure 1D) were exclusively affiliated to the genus Streptomyces among which the novel species Streptomyces lunaelactis1, and clustered into phylotypes distant from their soil-dwelling counterparts. The fact that the newly isolated Streptomyces are distantly related to already known species suggests that their specialized metabolism could be adapted to the specific cave environment and therefore possibly producing unique bioactive compounds. The moonmilk Streptomyces collection was found to display strong inhibitory activities against a wide range of human pathogens (Figure 1E), as 94, 71, and 94% of the isolates inhibited or impaired the growth of Gram-positive, Gram-negative bacteria, and fungi, respectively2. Attempts to identify the products of their ‘secondary metabolism’ are currently in progress and they already highlighted that numerous bioactive compounds have masses that do not match with the thousands of molecules already listed in natural compounds catalogues. Mining the genomes of the Streptomyces isolates also identified unique predispositions for natural products biosynthesis, giving hope for future identification of novel and useful antibiotics.

References

1Maciejewska et al. 2015. Streptomyces lunaelactis sp. nov., a novel ferroverdin A-producing Streptomyces species isolated from a moonmilk speleothem. Antonie Van Leeuwenhoek. 107(2):519-31.

2Maciejewska and Adam et al., 2016. A Phenotypic and Genotypic Analysis of the Antimicrobial Potential of Cultivable Streptomyces Isolated from Cave Moonmilk Deposits. Front Microbiol. 7:1455.

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