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Institute for Bioengineering and Biosciences
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Quantitative FRET Microscopy Reveals a Crucial Role of Cytoskeleton in Promoting PI(4,5)P2 Confinement

Quantitative FRET Microscopy Reveals a Crucial Role of Cytoskeleton in Promoting PI(4,5)P2 Confinement | iBB | Scoop.it

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is crucial to many cellular processes in eukaryotes, including membrane trafficking, signal transduction, ion channel function  and cytoskeleton dynamics. This function multiplicity is partially achieved through a dynamic spatiotemporal organization of PI(4,5)P2 within the membrane. In a recent paper published in IJMS, an IBB team (Maria J. Sarmento, Luís Borges-Araújo, Sandra N.Pinto, Nuno Bernardes, Joana Ricardo, Ana Coutinho, Manuel Prieto and Fábio Fernandes) was able to quantify PI(4,5)P2 confinement in living cells making use of FRET imaging measurements. PI(4,5)P2 was found to be significantly compartmentalized at the plasma membrane of HeLa cells. These PI(4,5)P2 enriched domains were shown to not depend on cholesterol content, ruling out an association with lipid rafts. On the other hand, upon inhibition of actin polymerization, compartmentalization of PI(4,5)P2 was almost entirely eliminated, confirming that the cytoskeleton network is the critical component responsible for the formation of nanoscale PI(4,5)P2 domains.

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iBB Researcher Nuno Bernardes is a Fulbright Visiting Scholar at the University of Pennsylvania

iBB Researcher Nuno Bernardes is a Fulbright Visiting Scholar at the University of Pennsylvania | iBB | Scoop.it

In cancer cells, the glycome is distinct from that on non-cancer cells, affecting the functionality of many overexpressed membrane oncogenes. In the scope of a visit to the laboratory of Prof. Elizabeth Rhoades at the University of Pennsylvania, Nuno Bernardes from BSRG-iBB will use advanced microscopy-based biophysical approaches to determine and quantify the molecular determinants involved in protein-glycan interactions between azurin(s)-derived peptides and cancer cells. This will make use of giant plasma membrane vesicles (GPMVs) originated from cell lines and primary tumor cells. The characterization of these interactions will foster the development nano-delivery systems like nanoparticles and exosomes engineered to surface display azurins-derived peptides to improve tumor treatments. The project and visit is supported by the Fulbright program, as described here. 

mesrallonges's comment, September 10, 2021 9:01 AM
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Burkholderia cenocepacia BCAM2418-induced Antibody Inhibits Bacterial Adhesion

Burkholderia cenocepacia BCAM2418-induced Antibody Inhibits Bacterial Adhesion | iBB | Scoop.it

B. cenocepacia is a contact-dependent bacterium known for its capacity of causing respiratory infections. Among a panel of adhesins used by B. cenocepacia to contact with host cells, trimeric autotransporter adhesins (TAAs) are of particular interest. In a recent paper published in Cellular Microbiology, a BSRG-iBB team (Andreia Pimenta, Nuno Bernardes, Dalila Mil-Homens and Arsénio M Fialho) together with Michelle Kilcoyne and Lokesh Joshi from the National University of Ireland Galway, Galway, Ireland, were able to uncover the roles of the TAA BCAM2418, as an adhesin and the type of host glycans that serve as recognition targets. This work reveals the importance of BCAM2418 as a mediator of early host-bacteria crosstalk.

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Production of Extracellular Vesicles Derived from Mesenchymal Stromal Cells in Bioreactors

Production of Extracellular Vesicles Derived from Mesenchymal Stromal Cells in Bioreactors | iBB | Scoop.it

Cell-based therapies have been showing unprecedented therapeutic potential, already changing the landscape of medical care. Extracellular vesicles are nanoparticles naturally secreted by cells, which are important mediators of intercellular communication in our organism and are able to mediate therapeutic effects from their cells of origin. These vesicles can also be used as drug delivery vehicles to target multiple diseases. In a paper recently published in Frontiers in Cell and Developmental Biology, iBB researchers in collaboration with iMM Lisboa, CQE-IST and the companies PBS Biotech and AventaCell Biomedical, developed a new strategy for the robust and scalable production of extracellular vesicles from mesenchymal stromal cells, using bioreactors and an animal serum-free cell culture supplement. This strategy, developed within the frame of the PhD Program in Bioengineering of Miguel de Almeida Fuzeta, is a relevant step towards the large scale production of extracellular vesicles form different human tissue sources, which are promising tools for the development of new therapies against a variety of diseases, from cardiovascular diseases to cancer.

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Twin Seminars on Dysfunctional Disordered Proteins and Anticancer Activity of Azurins

Twin Seminars on Dysfunctional Disordered Proteins and Anticancer Activity of Azurins | iBB | Scoop.it

The 3rd Edition of iBB seminars will continue on the 24th June with short talks from Ana Melo - "Untangling the role of dysfunctional disordered proteins in neurodegeneration at single molecule level" and Nuno Bernardes - "Exploring plasma membrane components' organization and dynamics as targets for azurins: their role in anticancer activity and selective uptake of therapeutics". Join us next monday (13h00 h, room 1.38, IST-Tagus Park) to learn more about Ana's and Nuno's research.

 

Photo details: 3D-model of oxidized Pseudomonas aeruginosa azurin (pdb 4AZU)

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Nuno Bernardes Wins Poster Prize at 3rd ASPIC Congress

Nuno Bernardes Wins Poster Prize at 3rd ASPIC Congress | iBB | Scoop.it

iBB researcher Nuno Bernardes was awarded one of the Poster Prizes sponsored by the European Association for Cancer Research at the 3rd Congress of ASPIC - Associação Portuguesa de Investigação em Cancro. The work entitled “Modulation of membrane properties and interaction with lipid rafts components GM-1 and caveolin-1 in cancer cells by azurin increases membrane fluidity and sensitivity to anti-cancer drugs” was developed at BSRG-iBB, led by Prof. Arsénio Fialho in collaboration with colleagues from the CQFM-IST, Sandra N Pinto and Fábio Fernandes.

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Azurin Modulates the Biophysical Properties of the Cancer Cells’ Plasma Membranes

Azurin Modulates the Biophysical Properties of the Cancer Cells’ Plasma Membranes | iBB | Scoop.it

In a recent paper published in Cell Cycle, a BSRG-iBB team led by Arsénio Fialho shows how the bacterial protein azurin modulates the plasma membranes’ biophysical properties of the lung adenocarcinoma A549 cancer cells. In collaboration with the group of Nuno Santos at IMM, and Fábio Fernandes (CQFM- IST), changes are detected through the nanoindentation of cells detected by Atomic Force Microscopy (AFM). AFM is a technique with increased importance in detecting and quantifying these changes, namely on elasticity and deformability which are then related to several cell processes such as adherence, signaling, invasion and proliferation. By causing such changes, azurin contributes to the sensitization of A549 cells to EGFR-targeted therapies, to which they are resistant, possibly improving the outcome of these clinical therapies in patients that may develop resistance.

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The Azurin-Derived Peptide CT-p19LC Exhibits Membrane-Active Properties and Induces Cancer Cell Death

The Azurin-Derived Peptide CT-p19LC Exhibits Membrane-Active Properties and Induces Cancer Cell Death | iBB | Scoop.it

The bacterial protein azurin shows an unexpected therapeutic effect against various types of cancer. This property seems to result from its unique structural and surface features. A 28-residue peptide (named p28) derived from the middle part of azurin has been subjected to various studies and reached two clinical trials phase I in US. In a recent paper published in Biomedicines, a iBB team (Ana Rita Garizo, Lígia Coelho, Sandra Pinto, Tiago Dias, Fábio Fernandes, Nuno Bernardes and Arsénio M Fialho) were able to identified another anticancer bioactive peptide (CT-p19LC) derived from the C-terminal of azurin. CT-p19LC proved to interact preferentially with cancer cells, causing a significative inhibition of cell proliferation in a dose dependent manner. Moreover, it is proposed that the mode of action of CT-p19LC involves perturbation or disruption of cancer cell membranes. Overall this study highlights the relevance of azurin as a source of bioactive peptides with potential application in cancer therapies.

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Gefitinib-Loaded p28-PLGA Nanoparticles Reduce Tumor Burden and Metastases in Lung Cancer

Gefitinib-Loaded p28-PLGA Nanoparticles Reduce Tumor Burden and Metastases in Lung Cancer | iBB | Scoop.it

p28 is a 28 amino acids peptide derived from the bacterial protein azurin. It possesses cell-penetrating capabilities showing preferential enter in cancer cells. Moreover it has been subject in US to two phase I clinical trials as a anticancer agent. In a recent paper published in Journal of Controlled Release, a iBB team (Garizo AR, Dias TP, Fernandes F, Bernardes N, Fialho AM) together with a i3S/UP team (Castro F, Martins C, Almeida A, Barrias CC, Sarmento B) were able for the first time to fabricate p28-functionalized PLGA nanoparticles (NPs) loaded with the EGFR tyrosine kinase inhibitor gefitinib. The results obtained indicate that these NPs interact preferentially with lung cancer cells due to their decoration with p28 peptide. In vitro cytotoxicity assays demonstrate biological activity of the NPs against lung cancer cancer cells. Finally, in vivo studies demonstrated a great potential of the p28-NPs in enhancing the therapeutic effects of gefitinib.

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Burkholderia cenocepacia Transcriptome During the Early Contacts with Giant Plasma Membrane Vesicles

Burkholderia cenocepacia Transcriptome During the Early Contacts with Giant Plasma Membrane Vesicles | iBB | Scoop.it

Burkholderia cenocepacia is a human contact-dependent pathogenic bacterium known for its capacity of causing severe opportunistic respiratory infections. B. cenocepacia uses a complex machinery for primary adherence with host cells. In a recent paper published in Scientific Reports, a BSRG-iBB team (Andreia Pimenta, Nuno Bernardes, Dalila Mil-Homens and Arsénio M Fialho) together with Marta M Alves from CQE, IST, have developed a RNASeq-based approach that led to identify adhesion candidate genes that were not previously reported in the context of a B. cenocepacia infection. This study presents a innovative technique in which their use Giant Plasma Membrane Vesicles (GPMVs) from a bronchial epithelial cell line as a cell-like alternative to investigate the steps involved in the adhesion process of B. cenocepacia.

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Conditioned Medium from Azurin-expressing MSC Demonstrates Anti-tumor Activity

Conditioned Medium from Azurin-expressing MSC Demonstrates Anti-tumor Activity | iBB | Scoop.it

Cell-based therapies can enhance the specificity of anti-cancer therapeutic agents. In this context, human mesenchymal stromal cells (MSC) hold a promising future as cell delivery systems for anti-cancer proteins due to their innate tropism for tumors. iBB researchers Marília Silva, Gabriel Monteiro, Arsénio Fialho, Nuno Bernardes and Cláudia Lobato da Silva, engineered human MSC through non-viral methods to secrete a human codon-optimized version of azurin (hazu), a bacterial protein with demonstrated anti-cancer activity towards different cancer models in vitro and in vivo. Upon treatment with conditioned media (CM) from these engineered cells, a decrease in cancer cell proliferation, migration and invasion was seen, and an increase in cell death was observed for breast and lung cancer cell models. The results achieved by SCERG- and BSRG-iBB researchers were published in Frontiers in Cell and Developmental Biology, Stem Cell Research section.

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Perturbing the Dynamics and Organization of Cell Membrane Components: A New Paradigm for Cancer-Targeted Therapies

Perturbing the Dynamics and Organization of Cell Membrane Components: A New Paradigm for Cancer-Targeted Therapies | iBB | Scoop.it

https://www.scoop.it/t/ibb/?&tag=Ars%C3%A9nio+FialhoUnlike the current paradigm of “one drug one target”, nowadays multiple-target approaches taking place at the cancer cell membrane are gaining much more relevance. The rational is based on the use of a new class of molecules that can exert significant changes in the dynamics and organization of cell membranes thereby affecting growth factor signaling, invasiveness and drug resistance. In a review published in a Special Issue “Receptor-Targeted Cancer Therapy” of the International Journal of Molecular Sciences, BSRG-iBB team members Nuno Bernardes and Arsenio M Fialho present and discuss novel approaches for cancer therapy, including the anticancer bacterial protein azurin.

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The Modulation of Membrane Biophysical Properties in Cancer Cells by Azurin and its Relation to Anti-cancer Drug Resistance

The Modulation of Membrane Biophysical Properties in Cancer Cells by Azurin and its Relation to Anti-cancer Drug Resistance | iBB | Scoop.it
Nuno Bernardes, will be giving a talk entitled “The modulation of membrane biophysical properties in cancer cells by azurin and its relation to anti-cancer drug resistance”, Monday the 17th April, at 12h30m, in room QA1.3, South Tower, IST (Alameda). The seminar will highlight progress made on the anti-cancer activity of the bacterial-derived protein azurin, particularly the modulation of membrane biophysical properties of cancer cells and the abrogation of drug resistance. Nuno Bernardes is currently a Post-Doctoral Fellow at BSRG-iBB. His research has focused on the understanding of how bacterial-derived proteins, or derived peptides, may have an impact in the management of human diseases, namely cancer, aiming at their therapeutic use. The talk is included in the 2nd Edition of iBB seminars.
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Molecular Profiling of Breast Cancer Model Reveals New Targets for the Anti-Cancer Protein Azurin

Molecular Profiling of Breast Cancer Model Reveals New Targets for the Anti-Cancer Protein Azurin | iBB | Scoop.it

BSRG researchers have unveiled new targets for the anti-cancer protein azurin using a breast cancer model. In a paper published jointly with colleagues from IPATIMUP in The International Journal of Biochemistry and Cell Biology, the team led by Arsénio Fialho describes the use of DNA microarrays to understand the effects of azurin in invasive breast cancer cells overexpressing P-cadherin. The gene transcription data gathered shows that apoptosis is induced and endocytosis is up-regulated to mediate the controlled process of azurin entry in cells. A number of genes coding for membrane receptors frequently overexpressed in breast cancer are down-regulated, suggesting that these new targets could be exploited in the future. Click on title to learn more.

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