El grupo de Nanobiotecnología del IBB-MRB, se complace en comunicar que NANOLIGENTE ha sido escogida por la Associació d’Empreses de Cerdanyola del Vallès-Cerdanyola Empresarial   para recibir el Reconocimiento a la Innovación del 2013. Este fue recogido por la CEO de la empresa, Dª. Montserrat Cano, el 23 de noviembre de 2023 a las 20 h en el Hotel Campus de la UAB, en el marco de la X Noche de Cerdanyola Empresarial. Este Reconocimiento premia las actividades de Nanoligent en el desarrollo de nuevos fármacos antimetastásicos que llevamos a cabo a través del proyecto RETOS COLABORACIÓN que está actualmente activo (New protein-based nanodrugs for the development of targeted tumor-agnostic therapy, con referencia CPP2026-00). Este proyecto involucra a nuestro grupo y al grupo dirigido por el Prof. Ramón Mangues en el Hospital de Sant Pau.

The Nanobiotechnology group of the IBB-MRB is pleased to announce that NANOLIGENT has been chosen by the  l’Associació d’Empreses de Cerdanyola del Vallès-Cerdanyola Empresarial  to receive the Innovation Award for 2013. The Award was given to the CEO of the company, Ms. Montserrat Cano, on November 23, 2023 at 8 p.m. at the UAB Campus Hotel, as part of the X Cerdanyola Business Night. This recognition rewards the activities of the company in the development of new anti-metastatic drugs that we carry out through the RETOS COLABORACIÓN project that is currently active (New protein-based nanodrugs for the development of targeted tumor-agnostic therapy, with reference CPP2021-008946). This project involves our group and the group led by Prof. Ramón Mangues at the Sant Pau Hospital.

Nanoplastics (NPs) are currently a main concern for environmental, animal and human health due to their potential to accumulate in different environmental compartments and provoke effects in living organisms. Nevertheless, neither these effects nor the interaction of NPs with the cellular machinery are well characterized, and only scattered information is available. In the present work, we focused on the interaction between NPs and fish cells, both intestinal cells and macrophages, in order to understand which cell organelles are targeted by polystyrene (PS)-NPs and how this could impact cell function. PS-NPs can pass through phospholipid membranes, entering cells via endocytosis, phagocytosis or passive transport. Once internalized, we found that PS-NPs co-localize with lysosomes but not with mitochondria. Moreover, using two types of fluorescent probe (H₂DCFDA and DHE) we demonstrated that NPs did not trigger the production of reactive oxygen species (ROS), which was corroborated by the fact that neither the oxidative consumption ratio (OCR) nor the extracellular acidification rate (ECAR) in mitochondrial respiration were altered. RNASeq data revealed clear interference by PS-NPs with lipid metabolism, peroxisomes and PPAR signaling. The M1/M2 balance critically determines tissue homeostasis when exposed to exogenous agents such as microorganisms or pollutants. Thus, the expression of different genes (il1β, tnfα, il6, il10, il12, cox2, mmp9, ppar a, b and g) was further assessed to characterize the macrophage phenotype M1 or M2, induced by PS-NPs. Overall, in this study we demonstrate that PS-NPs co-localize within lysosomes, both in macrophages and in intestinal cells of rainbow trout, but do not trigger ROS production nor alter mitochondrial respiration. In macrophages, PS-NPs modulate polarization towards the M2-like phenotype.

ABSTRACT

The dual aquaporin (Aqp1ab1/Aqp1ab2)-mediated hydration of marine teleost eggs, which occurs during oocyte meiosis resumption (maturation), is considered a key adaptation underpinning their evolutionary success in the oceans. However, the endocrine signals controlling this mechanism are almost unknown. Here, we investigated whether the nonapeptides arginine vasopressin (Avp, formerly vasotocin) and oxytocin (Oxt, formerly isotocin) are involved in marine teleost oocyte hydration using the gilthead seabream (Sparus aurata) as a model. We show that concomitant with an increased systemic production of Avp and Oxt, the nonapeptides are also produced and accumulated locally in the ovarian follicles during oocyte maturation and hydration. Functional characterization of representative Avp and Oxt receptor subtypes indicates that Avpr1aa and Oxtrb, expressed in the postvitellogenic oocyte, activate phospholipase C and protein kinase C pathways, while Avpr2aa, which is highly expressed in the oocyte and in the follicular theca and granulosa cells, activates the cAMP-protein kinase A (PKA) cascade. Using ex vivo, in vitro and mutagenesis approaches, we determined that Avpr2aa plays a major role in the PKA-mediated phosphorylation of the aquaporin subdomains driving membrane insertion of Aqp1ab2 in the theca and granulosa cells, and of Aqp1ab1 and Aqp1ab2 in the distal and proximal regions of the oocyte microvilli, respectively. The data further indicate that luteinizing hormone, which surges during oocyte maturation, induces the synthesis of Avp in the granulosa cells via progestin production and the nuclear progestin receptor. Collectively, our data suggest that both the neurohypophysial and paracrine vasopressinergic systems integrate to differentially regulate the trafficking of the Aqp1ab-type paralogs via a common Avp-Avpr2aa-PKA pathway to avoid competitive occupancy of the same plasma membrane space and maximize water influx during oocyte hydration

Aquesta trobada va ser promoguda i encapçalada per la directora nacional del programa de Biociències del Tecnológico, Belinda del Carmen Carrión. A banda de l’IBB, també van reunir-se amb el coordinador del Grau de Ciències Biomèdiques i la Vicedegana de Mobilitat i Promoció, de la Facultat de Biociències de la UAB, juntament amb una visita a l’Institut de Neurociències de la UAB.

L’interès de l’entitat se centrava en conèixer el nostre institut i cercar possibles acords amb grups de recerca de l’IBB, afins a l’àmbit biomèdic, per rebre estudiants pre-grau en pràctiques de la carrera de Biociències del Tecnológico.

Durant la seva estada van realitzar una visita a les nostres instal·lacions i a alguns serveis UAB, acompanyats per direcció i promoció, i es van reunir amb un total de 4 grups de recerca de l’IBB: (1) Enginyeria de Proteïnes i Nanomedicina, (2) Plegament de Proteïnes i Malalties Conformacionals, (3) Biosensors i Bioanàlisi, i (4) Integritat i Inestabilitat del Genoma.

A banda de les possibles estades d’estudiants pre-grau, també es van explorar potencials col·laboracions de recerca entre aquests grups de l’IBB i grups de recerca afins del Tecnológico de Monterrey, amb la possibilitat de buscar finançament bilateral en ment.

El Parc de Recerca de la UAB i la Universitat Autònoma de Barcelona, organitzen enguany la Fira de la Innovació, que tindrà lloc el proper 17 d’octubre de 2023 a les 9h a l’Hotel EXE Campus.

Aquest esdeveniment té per objectiu presentar la tecnologia, idees innovadores o capacitats tecnològiques de grups de recerca de la UAB, per tal de facilitar-ne la seva transferència al teixit empresarial. D’altra banda, també pretén generar xarxes de col·laboració dins i fora del Campus UAB.

Serà per tant un espai de trobada entre personal investigador, empreses, emprenedors, inversors i curiosos de la innovació, que es trobarà emmarcat dins de la #SetmanadelaInnovació de la UAB que neix amb l’objectiu d’apropar a la societat les tecnologies i coneixement innovador de la Universitat.

Cinc dels nostres grups de recerca de l’IBB tindran estand propi:

– Biologia Molecular de Llevats
– Nanobiotecnologia
– Plegament de Proteïnes i Malalties Conformacionals
– Biosensors i Bioanàlisi
– Bioinformàtica de la Diversitat Genòmica

A més a més també assistirà la Plataforma de Producció de Proteïnes, ubicada a l’IBB.

Si us interessa la recerca que fan i voleu saber més sobre el que us podrien oferir, registreu-vos a l’esdeveniment i passeu-los a veure pel seu estand o concerteu una reunió bilateral amb ells mitjançant la plataforma. Si doneu un cop d’ull a l’agenda de la jornada veureu que hi ha moltes més activitats previstes.

Us animem també a consultar la nostra pàgina web i en cas que detecteu alguna altra recerca de l’IBB o tecnologia associada que us pogués interessar, us poseu en contacte amb nosaltres escrivint-nos a promocio.ibb@uab.cat i així poder també concertar una trobada amb vosaltres durant la fira.

Us hi esperem a tots i a totes!

El passat divendres 30 de juny ens van visitar 25 estudiants d’instituts de Catalunya, que van participar al curs d’estiu que organitza el grup de Genètica Molecular Bacteriana dins del Programa Argó de l’Institut de Ciències de la Educació de la UAB:

“Què podem fer per reduir les resistències als antibiòtics?”

Durant aquest curs d’una setmana, els investigadors Daniel Yero, Andromeda Celeste, Marc Bravo i Isidre Gibert els han format a la Facultat de Biociències de la UAB i aquest divendres han vingut a l’IBB per conèixer les línies d’investigació que tenen centrades en la resistència dels antibiòtics. A més a més, els estudiants van preparar uns materials divulgatius molt macos per fomentar l’ús correcte dels antibiòtics, que es vanexposar en el nostre pati per tal que tots els investigadors i investigadores de l’institut els poguessin veure.

Appl Environ Microbiol. 2023 May 17:e0031723. doi: 10.1128/aem.00317-23. PMID: 37195181. 

ABSTRACT

Fluorescently labeled bacterial cells have become indispensable for many aspects of microbiological research, including studies on biofilm formation as an important virulence factor of various opportunistic bacteria of environmental origin such as Stenotrophomonas maltophilia. Using a Tn7-based genomic integration system, we report the construction of improved mini-Tn7 delivery plasmids for labeling of S. maltophilia with sfGFP, mCherry, tdTomato and mKate2 by expressing their codon-optimized genes from a strong, constitutive promoter and an optimized ribosomal binding site. Transposition of the mini-Tn7 transposons into single neutral sites located on average 25 nucleotides downstream of the 3′-end of the conserved glmS gene of different S. maltophilia wild-type strains did not have any adverse effects on the fitness of their fluorescently labeled derivatives. This was demonstrated by comparative analyses of growth, resistance profiles against 18 antibiotics of different classes, the ability to form biofilms on abiotic and biotic surfaces, also independent of the fluorescent protein expressed, and virulence in Galleria mellonella. It is also shown that the mini-Tn7 elements remained stably integrated in the genome of S. maltophilia over a prolonged period of time in the absence of antibiotic selection pressure. Overall, we provide evidence that the new improved mini-Tn7 delivery plasmids are valuable tools for generating fluorescently labeled S. maltophilia strains that are indistinguishable in their properties from their parental wild-type strains.

IMPORTANCE The bacterium S. maltophilia is an important opportunistic nosocomial pathogen that can cause bacteremia and pneumonia in immunocompromised patients with a high rate of mortality. It is now considered as a clinically relevant and notorious pathogen in cystic fibrosis patients but has also been isolated from lung specimen of healthy donors. The high intrinsic resistance to a wide range of antibiotics complicates treatment and most likely contributes to the increasing incidence of S. maltophilia infections worldwide. One important virulence-related trait of S. maltophilia is the ability to form biofilms on any surface, which may result in the development of increased transient phenotypic resistance to antimicrobials. The significance of our work is to provide a mini-Tn7-based labeling system for S. maltophilia to study the mechanisms of biofilm formation or host-pathogen interactions with live bacteria under non-destructive conditions.

ABSTRACT

Stenotrophomonas maltophilia is an environmental bacterium as well as an emerging opportunistic multidrug-resistant pathogen. They use the endogenous diffusible signal factor (DSF) quorum sensing (QS) system to coordinate population behavior and regulate virulence processes but can also respond to exogenous N-acyl-homoserine lactone (AHL) signals produced by neighboring bacteria. The effect of these QS signals on the global gene expression of this species remains, however, unknown. Whole-transcriptome sequencing analyses were performed for exponential cultures of S. maltophilia K279a treated with exogenous DSF or AHLs. Addition of DSF and AHLs signals resulted in changes in expression of at least 2-fold for 28 and 82 genes, respectively. Interestingly, 22 of these genes were found upregulated by both QS signals, 14 of which were shown to also be induced during the stationary phase. Gene functions regulated by all conditions included lipid and amino acid metabolism, stress response and signal transduction, nitrogen and iron metabolism, and adaptation to microoxic conditions. Among the common top upregulated QS core genes, a putative TetR-like regulator (locus tag SMLT2053) was selected for functional characterization. This regulator controls its own β-oxidation operon (Smlt2053–Smlt2051), and it is found to sense long-chain fatty acids (FAs), including the QS signal DSF. Gene knockout experiments reveal that operon Smlt2053–Smlt2051 is involved in biofilm formation. Overall, our findings provide clues on the effect that QS signals have in S. maltophilia QS-related phenotypes and the transition from the exponential to the stationary phase and bacterial fitness under high-density growth.IMPORTANCE The quorum sensing system in Stenotrophomonas maltophilia, in addition to coordinating the bacterial population, controls virulence-associated phenotypes, such as biofilm formation, motility, protease production, and antibiotic resistance mechanisms. Biofilm formation is frequently associated with the persistence and chronic nature of nosocomial infections. In addition, biofilms exhibit high resistance to antibiotics, making treatment of these infections extremely difficult. The importance of studying the metabolic and regulatory systems controlled by quorum sensing autoinducers will make it possible to discover new targets to control pathogenicity mechanisms in S. maltophilia.

Volume 164, August 2023, 114976

https://doi.org/10.1016/j.biopha.2023.114976

Abstract

Two human proteins involved in the inflammatory cell death, namely Gasdermin D (GSDMD) and the Mixed Lineage Kinase Domain-Like (MLKL) protein have been engineered to accommodate an efficient ligand of the tumoral cell marker CXCR4, and a set of additional peptide agents that allow their spontaneous self-assembling. Upon production in bacterial cells and further purification, both proteins organized as stable nanoparticles of 46 and 54 nm respectively, that show, in this form, a moderate but dose-dependent cytotoxicity in cell culture. In vivo, and when administered in mouse models of colorectal cancer through repeated doses, the nanoscale forms of tumor-targeted GSDMD and, at a lesser extent, of MLKL promoted CD8⁺ and CD20⁺ lymphocyte infiltration in the tumor and an important reduction of tumor size, in absence of systemic toxicity. The potential of these novel pharmacological agents as anticancer drugs is discussed in the context of synergistic approaches to more effective cancer treatments.

El passat dimecres 31 de maig de 2023, de la 1 a les 3 del migdia, es va celebrar un Taller de presentació de pòsters relacionats amb la genòmica de poblacions de les malalties infeccioses bacterianes a l’Aula Rosalind Franklin de l’IBB. 

En aquesta activitat van participar-hi un total de 28 alumnes de quart curs dels Graus de Genètica i Microbiologia, de la Facultat de Biociències de la UAB, que estan cursant l’assignatura optativa de Genòmica Bacteriana. Aquesta assignatura està coordinada per Daniel Yero, docent a la Facultat de Biociències i investigador del grup de Genètica Molecular Bacteriana de l’IBB.  

Es van presentar un total de 6 pòsters realitzats pels alumnes, que es van visualitzar durant l’esdeveniment i es van avaluar posteriorment, tot plegat acompanyat de cafè i pastes, com si es tractés d’una sessió de pòsters pròpiament d’un congrés científic.  

A banda de la sessió de pòsters, els estudiants van conèixer també les tecnologies de seqüenciació disponibles a l’IBB.  

Aquesta activitat ha estat una prova pilot de cara a poder-la implementar en cursos posteriors com un projecte d’innovació docent per facilitar que els alumnes s’apropin d’una forma real al món de la ciència.