2012-01-17

One of DIVINOCELL partners, Evolva, appeared in this month’s online version of The Scientist, in an article called Bioterrorist Battles, regarding a new drug they are developing, the EV-077, financed by a 5-year grant from the Pentagon’s Defense Threat Reduction Agency (DTRA).

EV-077 is a drug with a wide variety of uses, including possible future use as a treatment for diabetes, influenza and, what interests the DTRA most, Ebola virus.

2011-06-09

György Kéri, from Vichem, was invited by the European Commission to present a talk on how the participation in the FP7 impacts SMEs.

2011-06-01

The results from the publishable summary of the First Periodic Report of DIVINOCELL have been published in CORDIS Technology Marketplace.

MT.

2011-05-23

In parallel to the Molecular Dynamics simulation of the mechanical elements of the bacterial divisome polymers (FtZ, FtsA, etc.), a series of MD simulations were performed to study the role of protein interacting to evolutionary related cytoskeleton polymers. Cadherins form a large family of calcium-dependent cell-cell adhesion receptors involved in development, morphogenesis, synaptogenesis, differentiation and carcinogenesis through signal mechanotransduction using an adaptor complex that connects them to the cytoskeleton. However, the molecular mechanisms underlying mechanotransduction through cadherins remain unknown, although their extracellular region (ectodomain) is thought to be critical in this process. In order to access the atomic details of the structural changes taking place in the process, we performed MD simulations of the stretching of the entire ectodomain. By single-molecule force spectroscopy, molecular dynamics simulations and protein engineering, here we have directly examined the nanomechanics of the C-cadherin ectodomain and found it to be strongly dependent on the calcium concentration.

* Oroz J, Valbuena A, Vera AM, Mendieta J, Gómez-Puertas P, Carrión-Vázquez M. 2011. Nanomechanics of the cadherin ectodomain "canalization" by Ca2+ binding results in a new mechanical element. Journal of Biological Chemistry 286: 9405-9418.

PGP.

2011-04-30

Organised by György Kéry and Gábor Németh from Vichem Chémie Research Ltd., Budapest, the Second DIVINOCELL Annual Meeting was held at Hotel Budapest, Budapest, Hungary, from 14 to 15 April 2011.

35 scientists from the 11 project partners participated in this meeting. A total of 19 scientific talks reviewed the progress achieved since the first annual meeting (Cambridge, 2010). A special session dealt with the administrative and coordination tasks of the project.

MT.

2010-10-25

A summary of the DIVINOCELL project was presented on October 1, 2010 by Tanneke den Blaauwen at the European Inter-network meeting on antibiotic resistance. Representatives of the Aeropath, AntiPathoGN, Divinocell, EU-INTAFAR, Nabativi, PAR, Pneumopath and UC BACWAN were present. The meeting was organized by the Centre of Protein Engineering and the Doctoral School of Sciences (EDT: Structure and Function of Biological Macromolecules, Modelling and Bioinformatics) of the university of Liege and was held in the Chateau de Harze in Belgium. TdB.

2010-09-30

Nine out of the ten putative L. monocytogenes PBP genes were shown to encode proteins that bind derivatives of β-lactam antibiotics, thus enabling their positive identification. PBPD2 (Lmo2812) was not visualized in whole cell extracts, most probably due to its low abundance, but it was shown to bind Boc-FL after recombinant overexpression and purification. Mutants lacking Lmo2812 and another low molecular mass (LMM) PBP, PBP5 (PBPD1) - both with DD-carboxypeptidase activity - displayed only slight morphological alterations, demonstrating that they are dispensable for cell survival and probably participate in the latter stages of peptidoglycan synthesis. Since Lmo2812 preferentially degrades low-molecular- mass substrates, this may indicate a role in cell wall turnover.

*Korsak D, Markiewicz Z, Gutkind GO, Ayala JA. 2010. Identification of the full set of Listeria monocytogenes penicillin-binding proteins and characterization of PBPD2 (Lmo2812). Bmc Microbiology 10: 239.

J.A.

2010-08-18

Having a crucial role in bacterial cell division, FtsZ is a GTPase whose biochemical and structural properties are widely studied. The interest in FtsZ is justified both by its interesting functions, among them the constriction of the division ring is perhaps the most evident, and by its potential use as a tool to obtain new antimicrobials. Both aspects are part of the objectives investigated by several DIVINOCELL participants. A review on the FtsZ-directed mechanisms to constrict bacteria, authored by the DIVINOCELL researchers working at the CSIC and BioMol, together with one colleage from Hospital Universitario La Paz, has been published in Trends in Microbiology (1). The authors have summarized the knowledge on the FtsZ polymerization process and the GTPase activity. Recent results derived from mathematical modelling and reconstruction of the Zring outside the living cell are also discusssed.

1) J. Mingorance, G. Rivas, M. Velez, P. Gomez-Puertas, and M. Vicente. 2010. Strong FtsZ is with the force: mechanisms to constrict bacteria. Trends Microbiol. 18: 348-356.

2010-08-17

Piotr Szwedziak (from Jan Lowe's team, at MRC- Laboratory of Molecular Biology, Cambridge), has been awarded the prize sponsored by Molecular Microbiology for his poster "Biochemical and structural studies of the FtsZ/FtsA complex" presented at the 2010 Gordon Conference on Bacterial Cell Surfaces (New London, NH, USA. June 27- July 2, 2010). These results have been obtained within the framework of DIVINOCELL. MV.

2010-06-18

The DIVINOCELL team at the Spanish Centro Nacional de Biotecnología (CSIC) has published evidence showing that deprivation of FtsN, the last essential bacterial division protein in the hierarchy of divisome assembly, causes the disassembly of other elements from the division ring, even extending to already assembled proto-ring proteins (1). Up to now, it was assumed that the stability of the already assembled proto-ring, containing the essential division proteins FtsZ, FtsA and ZipA, should not be affected by division proteins that joined the divisome later. However, tracking the fate of the divisome components by fluorescence microscopy in the absence of FtsN, this study shows that divisome stability is not guaranteed until FtsN is recruited. The authors find that, as the FtsN level drops, each component from the already formed ring is dislodged following an inverse sequential pathway relative to the sequence of assembly. Restoration of FtsN levels allows for a quick reassembly of proto-rings. They have also found that in filaments in which FtsZ, instead of FtsN, has been depleted, the reassembly is even faster when its levels are restored. As FtsZ is the first protein in joining the proto-ring, they suggest that the recruitment of ZipA into incomplete FtsZ-FtsA proto-rings present in the FtsN-deprived filaments may require a period for the reversal of these partial assemblies before new active rings are assembled, while the assembly de novo in FtsZ-deprived filaments does not need any previous rearrangement of these proteins.

(1) Rico AI, García-Ovalle M, Palacios P, Casanova M, and Vicente M. 2010. Role of Escherichia coli FtsN protein in the assembly and stability of the cell division ring. Mol. Microbiol. 76(3), 760-771.