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Fellermann H.,Northumbria University | Fellermann H.,Barcelona Biomedical Research Park | Krasnogor N.,Northumbria University | Krasnogor N.,European Center for Living Technology
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2014

Biological systems employ compartmentalisation in order to orchestrate a multitude of biochemical processes by simultaneously enabling "data hiding" and modularisation. In this paper, we present recent research projects that embrace compartmentalisation as an organisational programmatic principle in synthetic biological and biomimetic systems. In these systems, artificial vesicles and synthetic minimal cells are envisioned as nanoscale reactors for programmable biochemical synthesis and as chassis for molecular information processing. We present P systems, brane calculi, and the recently developed chemtainer calculus as formal frameworks providing data hiding and modularisation and thus enabling the representation of highly complicated hierarchically organised compartmentalised reaction systems. We demonstrate how compartmentalisation can greatly reduce the complexity required to implement computational functionality, and how addressable compartments permit the scaling-up of programmable chemical synthesis. © 2014 Springer International Publishing.


Farres J.,Hospital del Mar Medical Research Institute | Martin-Caballero J.,Barcelona Biomedical Research Park | Martinez C.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas | Lozano J.J.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas | And 9 more authors.
Blood | Year: 2013

Hematopoietic stem cells self-renew for life to guarantee the continuous supply of all blood cell lineages. Here we show that Poly(ADP-ribose) polymerase-2 (Parp-2) plays an essential role in hematopoietic stem/progenitor cells (HSPC) survival under steady-state conditions and in response to stress. Increased levels of cell death were observed in HSPC from untreated Parp-2 -/- mice, but this deficit was compensated by increased rates of self-renewal, associated with impaired reconstitution of hematopoiesis upon serial bone marrow transplantation. Cell death after γ-irradiation correlated with an impaired capacity to repair DNA damage in the absence of Parp-2. Upon exposure to sublethal doses of γ-irradiation, Parp-2 -/- mice exhibited bone marrow failure that correlated with reduced long-term repopulation potential of irradiated Parp-2-/- HSPC under competitive conditions. In line with a protective role of Parp-2 against irradiation-induced apoptosis, loss of p53 or the pro-apoptotic BH3-only protein Puma restored survival of irradiated Parp-2-/- mice, whereas loss of Noxa had no such effect. Our results show that Parp-2 plays essential roles in the surveillance of genome integrity of HSPC by orchestrating DNA repair and restraining p53-induced and Puma-mediated apoptosis. The data may affect the design of drugs targeting Parp proteins and the improvement of radiotherapy-based therapeutic strategies. © 2013 by The American Society of Hematology.


Nicolas L.,Barcelona Biomedical Research Park PRBB | Nicolas L.,University of Murcia | Martinez C.,University of Murcia | Baro C.,Barcelona Biomedical Research Park | And 9 more authors.
Oncogene | Year: 2010

Poly(ADP-ribose) polymerase-2 (Parp-2) belongs to a family of enzymes that catalyse poly(ADP-ribosyl)ation of proteins. Parp-2 deficiency in mice (Parp-2-/-) results in reduced thymic cellularity associated with increased apoptosis in thymocytes, defining Parp-2 as an important mediator of T-cell survival during thymopoiesis. To determine whether there is a link between Parp-2 and the p53 DNA-damage-dependent apoptotic response, we have generated Parp-2/p53-double-null mutant mice. We found that p53-/- backgrounds completely restored the survival and development of Parp-2 -/- thymocytes. However, Parp-2-deficient thymocytes accumulated high levels of DNA double-strand breaks (DSB), independently of the p53 status, in line with a function of Parp-2 as a caretaker promoting genomic stability during thymocytes development. Although Parp-2-/- mice do not have spontaneous tumours, Parp-2 deficiency accelerated spontaneous tumour development in p53-null mice, mainly T-cell lymphomas. These data suggest a synergistic interaction between Parp-2 and p53 in tumour suppression through the role of Parp-2 in DNA-damage response and genome integrity surveillance, and point to the potential importance of examining human tumours for the status of both genes. © 2010 Macmillan Publishers Limited All rights reserved.


Puga I.,Barcelona Biomedical Research Park | Cols M.,Mount Sinai School of Medicine | Cerutti A.,Barcelona Biomedical Research Park | Cerutti A.,Mount Sinai School of Medicine | Cerutti A.,Catalan Institution for Research and Advanced Studies
Journal of Allergy and Clinical Immunology | Year: 2010

The intestinal mucosa contains large communities of commensal bacteria that process otherwise indigestible food components, synthesize essential vitamins, stimulate the maturation of the immune system, and form an ecologic niche that prevents the growth of pathogenic species. Conversely, the intestine provides the commensals with a stable habitat rich in energy derived from the ingested food. A delicate homeostatic balance maintains this mutualistic relationship without triggering a destructive inflammatory response. Commensals orchestrate intestinal homeostasis by entertaining an intimate dialogue with epithelial cells and immune cells lodged in the mucosa. Such a dialogue generates finely tuned signaling programs that ensure a state of hyporesponsiveness against noninvasive commensals and a state of active readiness against invasive pathogens. In this dialogue epithelial cells function as " interpreters" that continuously translate microbial messages to "instruct" immune cells as to the antigenic composition of the intestinal lumen. This education process initiates sophisticated defensive strategies that comprise massive production of IgA, a noninflammatory mucosal antibody class that generates immunity while preserving homeostasis. © 2010 American Academy of Allergy, Asthma & Immunology.


Gutierrez-Gallego R.,Bio analysis Group | Gutierrez-Gallego R.,University Pompeu Fabra | Gutierrez-Gallego R.,Barcelona Biomedical Research Park | Llop E.,Bio analysis Group | And 7 more authors.
Analytical and Bioanalytical Chemistry | Year: 2011

Doping analysis relies on the determination of prohibited substances that should not be present in the body of an athlete or that should be below a threshold value. In the case of xenobiotics their mere presence is sufficient to establish a doping offence. However, in the case of human biotics the analytical method faces the difficulty of distinguishing between endogenous and exogenous origin. For this purpose ingenious strategies have been implemented, often aided by state-of-the-art technological advancements such as mass spectrometry in all its possible forms. For larger molecules, i.e. protein hormones, the innate structural complexity, the heterogeneous nature, and the extremely low levels in biological fluids have rendered the analytical procedures heavily dependent of immunological approaches. Although approaches these confer specificity and sensitivity to the applications, most rely on the use of two, or even three, antibody incubations with the consequent increment in assay variability. Moreover, the requirement for different antibodies that separately recognise different epitopes in screening and confirmation assays further contributes to differences encountered in either measurement. The development of analytical techniques to measure interactions directly, such as atomic force microscopy, quartz crystal microbalance or surface plasmon resonance, have greatly contributed to the accurate evaluation of molecular interactions in all fields of biology, and expectations are that this will only increase. Here, an overview is provided of surface plasmon resonance, and its particular value in application to the field of doping analysis. [Figure not available: see fulltext.] © 2011 Springer-Verlag.

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