iBB

Ana Melo delivered an oral presentation at the 1st ML4NGP Meeting on Machine Learning and Non-Globular Proteins, Bratislava- Slovakia (July 2023). Her presentation was focused on mapping the structural transitions of the flanking polyQ regions in huntingtin exon 1 upon membrane binding, and its implications in Huntington´s disease. 

AM Melo was also elected for co-Leader of Working Group 4 of this ML4NGP COST-action. This group aims to improve the functional characterization of non-globular proteins (NGPs) and to understand the major questions involving NGPs. They include “conformational heterogeneity, evolution, conserved motifs, protein-protein interactions, liquid–liquid phase separation (LLPS) and involvement in neurodegenerative diseases.”

Extracellular vesicles (EVs) are small membrane bound structures released by cells into the extracellular space. They have been shown to transport different molecules such as proteins, nucleic acids and lipids to other cells, serving as vehicles of intracellular communication. EVs have also been shown to play important roles during viral and bacterial infection. Viruses can hijack the biogenesis of EVs to promote viral spreading. Additionally, these EVs are also important mediators in inflammation and immune responses during both bacterial and viral infections. A recent publication in the journal Pharmaceutics, by Diogo Gonçalves, Sandra Pinto and Fábio Fernandes (from iBB/IST), reviews these mechanisms and described the impact of bacterial EVs in regulating immune. Finally, the review also focuses on the potential and challenges of using EVs to tackle infectious diseases.

Vasco Bonifácio (iBB-i4HB/DBE) is the new President of the Lisbon Regional Delegation of the Portuguese Chemical Society (SPQ). Elections took place on June 1, 2023, with a three-year term. The new team includes Doctor Sandra Pinto (iBB-i4HB) and Doctor Rita Pires (CEFEMA), both IST researchers. It is incumbent upon the Delegations to develop, on a regional scale, the scientific and administrative activities arising from the achievement of the Society's purposes.

The CryoEM-PT - National Advanced Electron Microscopy Network for Health and Life Sciences facility inauguration was held in February 2nd at the INL - International Iberian Nanotechnology Laboratory, in Braga. The inauguration took place in the presence of Interim INL Director General - Paulo Freitas, the Scientific Coordinator of AEMIS Facility - Paulo Ferreira, the Alderwoman of Braga - Olga Pereira, the FCT President - Madalena Alves and CCDR-N President - António Cunha, along with the representatives of the multiple nodes of this network. Profs. Berberan Santos (iBB President), Fábio Fernandes (IST Node) and Manuel Prieto (iBB) attended the inauguration. IST is one of the nodes of the network and iBB is the authorized user of the equipment on behalf of IST within this network.

Ana M Melo participated as secondary proposer in the grant application of the COST Action: Non-globular proteins in the era of Machine Learning (ML4NGP). The action was recently funded and started in October 2022. Ana M Melo was selected to be part of the Management Committee and the first meeting already took place with decisions on the budget allocation/organization and future meetings. This COST-action is focused on non-globular proteins that comprise “intrinsically disordered regions, repeats, low-complexity sequences, aggregation-prone and phase-separating sequences, and are implicated in a range of age-related diseases”. The network combines both experimentalists and computational researchers. 

Professor Martin Hof, director of the J. Heyrovský Institute of Physical Chemistry in Prague,  gave a talk on the topic "Protein hydration and dynamics seen by fluorescence: TDFS (Time-Dependent Fluorescence Shifts) and PET-FCS (Photo-induced Electron Transfer- Fluorescence Correlation Spectroscopy)” on November 4, 2022.

Professor Martin revisited some of the principles relevant for synthetic biology as well as the importance of TDFS and PET-FCS to study relaxation dynamics of polar solvents and to probe protein dynamics on short time scales, and their relevance for the elucidation of enzyme activity.

This talk was framed during Professor Martin´s scientific visit to iBB.

Ana Melo gave an invited talk during the XVII Meeting of the Portuguese Society for Neuroscience, at Coimbra, 1 - 3 December, 2021. She presented recent work focused on characterizing the distinct conformational dynamics of the flanking polyQ regions in the membrane-bound state of Huntington exon 1, and its role in Huntington´s disease. Her presentation was in the framework of the SPB Symposium: “A biophysical perspective on degenerative diseases: protein assembly and phase separation”, together with Sandra Macedo Ribeiro (IBMC- i3S) and Salvador Ventura (IBB-Universitat Autonoma de Barcelona).

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.

Polyurea oxide (PURO) biodendrimers are a class of dendrimers that can trigger osteogenic differentiation of human mesenchymal stem cells (hMSCs). The effect of PURO biodendrimers in the differentiation of hMSCs was found by the single addition to a standard growth medium for MSCs differentiation (without differentiation inducers, e.g. dexamethasone, ascorbic acid, and β-glycerophosphate). These results, published in ACS Applied Bio Materials by Rita Pires and Vasco Bonifácio from BSIRG-iBB and with colleague João Conde from NOVA Medical School, constitute the first report of in vitro osteodifferentiation fully regulated by synthetic soft polymers. The outstanding role of dendrimers in nanomedicine, under clinic translation, combined with this feature is envisaged to foster PURO dendrimers as an important strategy in cell therapy and regenerative medicine.

Sandra Pinto and Vasco Bonifácio (iBB-i4HB/IST) were invited to carry out hands-on science activities for 1st cycle students at EB/JI Quinta da Cevadeira School on May 31, 2023. At the “Clube Ciência Viva – Cientistas de Palmo e Meio” they performed several experiences based on fluorescence and phosphorescence. The “little scientists” were surprised by the luminescent properties of different materials used in everyday life (emergency signs, honey, olive oil, gummy bears, vitamins, among others), learned how to make fluorescent slime and also discovered the fireflies chemistry.

Vasco Bonifácio (iBB-i4HB/DBE) was one of the guest speakers at the Workshop “Design and trends in presentations” that took place at Academia das Ciências on May 26, 2023, as part of the 5th Edition of CQE Days, Researchers Meeting from Centro Estrutural de Química (CQE) at IST. His talk “Design or redesign?” focused on strategies to improve the graphic quality of science communication. Based on his experience as an Editor of scientific journals, Researcher and Professor, he used several case studies, where he approached the construction of figures and graphical abstracts for articles, and the elaboration of posters and slides for oral presentations.

Fluorescence microscopy and spectroscopy are routine tools in basic and applied biological sciences. An expanding library of organic fluorophores and fluorescent proteins with radically different properties are available, offering great flexibility to the user of fluorescence methods. Still, a considerable fraction of casual users of fluorescence tools do not follow rational considerations when selecting a probe. In a recently published book chapter, Fábio Fernandes (iBB) and Maria Sarmento (IMM) provide an overview of the most important factors to weight when selecting a fluorophore. A list of different fluorophores and a summary of their properties and labeling strategies is presented as a tool to assist in the process of choosing a fluorescent probe.

A pandemic can turn the world upside down. We recently had this hard experience, which made us reflect (a lot) on the importance of science and how it is the stronghold of our survival as a species (we have persisted for at least 200 thousand years!). Resistance to antibiotics and antifungals is nothing new and seems to have become commonplace (or despised). It is too serious a problem to be reassured, for several reasons. The evolution of multidrug resistance in bacteria and fungi (proven by genetic sequencing), associated with the disinvestment in new drugs by large pharmaceutical multinationals, converges in a (next) pandemic scenario of hypervirulent bacteria and fungi. Antimicrobial resistance is fundamentally based on the ability that bacteria and fungi have acquired to escape the action of available drugs, using mainly three strategies: enzymatic degradation of drugs, alteration of drug target proteins, and alteration of membrane permeability (expression of efflux pumps). Bearing in mind these strategies, a team of researchers from iBB-IST (led by Prof. Vasco Bonifácio) in collaboration with researchers from CQE-IST and ITQB-NOVA, designed, and produced antimicrobial polyurea pharmadendrimers, a new class of antibiotics and antifungals. These pharmadendrimers have excellent activity (in vitro and in vivo) against multidrug-resistant bacteria and fungi from clinical isolates collected in Portuguese hospitals and clinics. Their administration is safe as they have a very wide therapeutic window, in which they are not cytotoxic and do not cause hemolysis (the main problems of other analogues under investigation, such as antimicrobial peptides). On the other hand, its mechanism of action prevents the development of resistance, an almost impossible mission for bacteria and fungi because it requires a restructuring of their membrane. Antimicrobial pharmadendrimers have been patented, and an international patent application is pending. In an interview to the RTP TV channel, on the program “O Desafio do Superior em Portugal”, Dr. Rita Pires, a researcher on the team, talks about this invention (video). The research work was recently published in a high impact international journal.

In a recent study led by Pedro Gois´s team (Faculdade Farmácia da Universidade de Lisboa), with collaboration from researchers Hovione FarmaCiencia SA and iBB (Sandra Pinto), a novel multivalent platform of NHS-activated acrylates was developed for the site-selective chemical appendage of multiple functionalities on native peptides. The results were published in Chem Commun and were included in the 2022 issue of Pioneering Investigators.

Ana M. Melo was a recipient of a 2022 Biophysical Travel Award for Scientists within 10-years after completing the PhD. She was honored during the Travel Awardee Reception by the Society’s Committees for Inclusion/Diversity and Professional Opportunities for Women. This highly competitive award covered her travel expenses to San Francisco, California (US).

A new strategy to modify cellulose with the short antimicrobial hexapeptide MP196 (RWRWRW-NH2) is proposed by BERG and BSIRG researchers that uses fusions of Cys-terminated derivatives of MP196 and a carbohydrate binding module (CBM). CBM3-MP196-modified cellulose hydrogels displayed antibacterial activity that was significantly higher when compared with controls. This versatile concept offers a toolbox for the functionalization of different cellulose materials with a broad choice in peptides. the paper was published in Acta Biomaterialia. The work was funded by project CBM-X.

Lipid hydroperoxides have recently been recognized as key mediators of diseases (such as neurodegenerative disorders or Type II diabetes) and cell death. In a recent work, structural and dynamic perturbations induced by the hydroperoxidized POPC lipid (POPC-OOH) in fluid POPC membranes were addressed using advanced small-angle X-ray scattering (SAXS) and fluorescence methodologies. Notably, this multidisciplinary approach revealed that the hydroperoxide group located at the membrane interface, promotes a higher membrane hydration and microviscosity, with a strikingly lower order and bending rigidity, an unusual trend in membrane biophysics, which ultimately compromises membrane structure organization. This international work co-led by Ana M. Melo (BSIRG-iBB) and Rosangela Itri (Institute of Physics, University of São Paulo) was recently published in Langmuir and involved other BSIRG-iBB researchers (Ana Coutinho, Alexander Fedorov and Manuel Prieto).

The role of the cell wall in yeast response and tolerance to stress is frequently neglected. A BSRG-iBB research paper just published in Scientific Reports, provides, for the first time, a comprehensive view of the alterations occurring at the cell wall in a yeast population adapting to sub-lethal stress induced by acetic acid. The results reveal changes to the cell wall polysaccharide composition and nanomechanical properties, as well as alterations in the transcript levels of key cell wall biosynthetic genes. This paper reinforces the notion that the adaptive yeast response to acetic acid involves coordinated alterations of the cell wall at the biophysical and molecular levels. The gathered knowledge is important for the design of superior industrial strains and for the efficient control of the deleterious activity of spoilage yeasts, particularly in the Food Industry. This research work is first-authored by the PhD student of the PhD programme in Biotechnology and Biosciences Ricardo Ribeiro (FCT_DP AEM fellowship), performed under the supervision of Isabel Sá-Correia. This collaborative study with Fábio Fernandes (BSIRG-iBB) and Mário S. Rodrigues and his team (BioISI, Faculty of Sciences, ULisboa), is also coauthored by Cláudia Godinho (posdoc researcher) and the PhD student Nuno Bourbon-Melo (FCT_DP BIOTECnico) from the BSRG-iBB team.

Vasco Bonifácio was invited to participate in the program “Explain me as if were 5 years old”, an IST initiative that consists of informal conversations about science for curious children and adults. In this program, which was broadcast live on Facebook on the afternoon of November 28, 2020, Vasco presented the session “Why do fireflies shine?”. In this session, chaired by Joana Lobo Antunes (Communication and Public Relations Office of IST), Vasco Bonifácio explained the phenomena of bioluminescence, chemiluminescence and phosphorescence and how these physical-chemical processes are related to research in the area of cancer treatment that he has been developing in recent years. There was also time to carry out live experiments, which delighted the young audience and to answer many questions! The program was recorded and is available on the program's website (Episode 12).