The presence of genotoxic impurities (GTIs) (e.g. reagents, intermediates, side-products) in active pharmaceutical ingredients (APIs) constitutes a high risk for human health. For this reason, regulatory authorities have established that the intake of these DNA reactive impurities should not exceed the threshold limit of 1.5 µg/day. In a recent study published in the journal Separation and Purification Technology, Teresa Esteves and Frederico Ferreira from BERG-iBB, in collaboration with researchers from Hovione and FCT-UNova, present a novel molecular imprinted polymer (MIP) that is able to efficiently remove the GTI 4-dimethylaminopyridine at concentrations as high as 1 g/L. Two case studies relevant for the pharmaceutical industry are evaluated, and a multistep configuration is proposed comprising a MIP-based step and organic solvent nanofiltration, that reduces GTI content below the limits imposed by law. Click on title to learn more.
Inês Pinto has received the 1st best poster award at the International Symposium ISPPP 2016 for her communication entitled "On chip chromatography for rapid screening of multimodal ligand-target interactions". This project arises from a collaboration between Ana Azevedo from BERG-iBB and João Pedro Conde from INESC-MN. Inês is currently in her 3rd year of doctoral studies in Biotechnology and Biosciences at Instituto Superior Técnico. Congratulations Inês!
Acetic acid accumulation inhibits yeast growth and fermentation, impairing many yeast-based biotechnological processes, in particular lignocellulosic biorefineries. A recent study published in Biochemical Journal, performed by BSRG-iBB researchers led by Prof. Isabel Sá-Correia and started in the framework of the PhD in Biotechnology and Bioscience of Joana Guerreiro, in collaboration with researchers from Jeremy Thorner´s Lab at University of California, Berkeley, demonstrated that acetic acid tolerance requires sphingolipid biosynthesis. This process is mediated by the TORC2-dependent Ypk1 kinase, a key regulator of the sphingolipid biosynthetic pathway. It was thus proposed the manipulation of the flux into the sphingolipid biosynthetic pathway as a novel rational way to increase acetic acid tolerance of industrial yeast strains.
"The PathoYeastract database, a repository of data on transcription regulation occurring in pathogenic yeasts responsible for the development of candidiasis in humans, has just been launched. The knowledge gathered therein by researchers from BSRG-iBB and INESC-ID was extracted from hundreds of publications. The database provides researchers in the field with computational tools that are crucial for the design of improved strategies for the diagnosis and treatment of life-threatening yeast infections. Click on title to learn more."
A team of researchers from BERG-iBB led by Joaquim Cabral and Pedro Fernandes is part of an international consortium awarded with an EraNet-Industrial Biotechnology grant to fund the multilateral research project "Polybugs - In vivo cascades for sustainable access to monomers of high volume polymers". The project aims at the development/improvement of a microbial cell factory platform for the biotechnological production of polymer precursors. It considers various aspects with regard to the expression of heterologous pathways, reaction and reactor engineering. The project combines systems biology and industrial biotechnology/process engineering. Apart from iBB, the consortium includes research groups from Helmholtz Center for Environmental Research (UFZ, team leader), ifu Hamburg GmbH, Norwegian University of Science and Technology (NTNU) and the industrial partner Evonik Creavis GmbH.
Photo: Cultures of Pseudomonas spp. by Howard F. Schwartz [CC BY 3.0], Colorado State University, Bugwood.org, via Wikimedia commons.
Carla da Conceição Caramujo Rocha de Carvalho, researcher and principal investigator from BERG-iBB, has received an honorable mention in the area of Biology, Biological Engineeering, Biochemistry and Biotechnology of the Universidade de Lisboa/Caixa Geral de Depósitos awards of 2016. Over the last year, Carla's research has focused on the areas of bacterial stress, lipidomics and marine biotechnology. The goal of the Universidade de Lisboa/Caixa Geral de Depósitos awards is to recognize scientific research activities and to promote the publication in high-quality international journals. The award was handed over on the 25th July, during the cerimonies of the third aniversary of the University of Lisbon.
Alachlor has been widely used as an herbicide worldwide. Concerns regarding current and legacy ecological risks, particularly in worst-case situations associated with accidental herbicide contamination, have been raised. In the EU, alachlor is in the list of priority substances in the field of water policy. A joint publication from Cristina A. Viegas and Fátima N. Gil (former PhD student) of BSRG-iBB and Gemma Bellí from the University of Lleida, Spain, in the journal Environmental Microbiology, contributes new information to better understand the potential deleterious short-term effects of alachlor in the S. cerevisiae eukaryotic model. Results point to possible links between alachlor toxicity and perturbations in metal and antioxidant homeostases, which may be relevant for environmental microbes and higher eukaryotes in situations of inadvertent high herbicide contamination. Click on title to learn more.
The 6th International Conference on Physiology of Yeasts and Filamentous Fungi (PYFF6) took place from 11-14 July 2016 at Instituto Superior Técnico (IST), organized by BSRG-iBB team members and chaired by Professor Isabel Sá Correia. The Conference was organized under the auspices of the Section of Microbial Physiology of EFB (European Federation of Biotechnology) with the support of FEMS (Federation of the European Microbiology Societies) and SPM (Portuguese Society of Microbiology). The scientific program focused on the genome-wide approaches that are unveiling fascinating aspects of the physiology of yeasts and filamentous fungi and boosting the understanding of these systems. The 9 thematic sessions, with 27 keynote presentations and 27 oral presentations selected from the submitted abstracts, covered a broad scope of research topics and experimental approaches. The 150 posters presented provided the perfect platform for fruitful discussions and the establishment of collaborations. The conference program also included the Workshop “Starting New Companies in Yeast and Fungal Biotechnology”. Attendees came from 33 countries (22 EU countries) and more than 97 institutions were represented, including 16 international biotech companies. Around 100 students were actively present, 28 of them supported by meeting grants from FEMS and EFB. Click on title to learn more.
Enzymes are key ingredients in food and feed processing due to their ecofriendly nature and specificity of action. Accordingly, enzymes fulfill several roles, mostly as additives and food processing aids, but they are also used to provide new and green production processes and new products. In a book chapter recently published, Pedro Fernandes (BERG-IBB, IST, ULisboa) presents an updated perspective on the use of enzymes to promote novel biotransformations leading to a new range of compounds, goods and formulations with impact in the food and beverage industries.
Image: 3D structure of Alpha-glucosidase from Thermotoga maritima, an enzyme involved in breaking down complex carbohydrates.
Challenge: Can we implement systems and synthetic biology strategies, as well as metagenomic tools to gain full understanding of biological systems and enable their redesign and construction in order to display functions more suited to specific biotechnological applications?
Strategic Goal: Strengthening and consolidation of post-genomic technologies to support and leverage iBB research in biosciences and bioengineering.
Challenge: Can we improve the bioprocessing of human stem cells and their derivatives to streamline applications in Cell Therapies, Regenerative Medicine and Toxicology/Pharmacological testing?
Strategic Goal: To develop innovative engineering approaches to speed the translation of emerging stem cell science discoveries, tools and technologies into cellular and molecular therapies with significant impact on healthcare innovation and patient lifes.
A US Patent application (application number 14/817063) co-authored by Arsénio Fialho from BSRG-iBB and by researchers from the University of Illinois headed by Prof. Ananda Chakrabarty has just been published. The innvention relates to compositions and methods of use of cupredoxins, and variants, derivatives and structural equivalents of cupredoxins that interfere with the ephrin signaling system in mammalian cells. Specifically, the invention relates to uses of cupredoxins, such as azurin, rusticyanin and plastocyanin, and variants, derivatives and structural equivalents thereof, to treat cancer in mammals. Click on title to learn more.
Photo: 3D model of Rusticyanin from Thiobacillus ferrooxidans.
The Director of iBB, Professor Joaquim Cabral, will be giving a seminar entitled "Bioprocess Engineering Strategies for Stem Cell-based Therapies and Regenerative Medicine" at the Distinguished Seminar Series of Imperial College London. The Series, which is organised by the Department of Chemical Engineering, is aimed at exploring the views from distinguished academics from around the world in shaping the future of Chemical Engineering, the profession and its research agenda. The talk will be delivered at 9:30 on Monday 27th (Roderic Hill Building, room C616). Click on title to learn more.
Description: Microscopic structure of chromatographic paper (100 Xs), featured photo by Ana Rosa and Miguel Prazeres, Copyright BERG-iBB 2016.
Context: BERG researchers led by Miguel Prazeres are developing paper-based biosensors for molecular diagnostics by combining affinity-based anchoring of biomolecules with nanoparticle-based detection. The work is being performed in the context of iBB’s Strategic Area 2: Advanced Bioprocess Engineering.
iBB was recently represented at the International Symposium ISPPP 2016 by researchers from BERG's Bioseparation Engineering Lab, who presented 3 oral communications (Raquel Aires-Barrros, Ana Azevedo and Emanuel Capela) and 2 poster communications (Sara Rosa and Inês Pinto).
Mycolata form a group of Gram-positive bacteria, which includes Rhodococcus and Mycobacterium strains, containing long chain α-alkyl-β-hydroxy fatty acids. These cells are known for their high tolerance against antibiotics and both aromatic and aliphatic hydrocarbons. In a recent publication in the journal AMB Express, Dr. Carla CCR de Carvalho (BERG-iBB) and a team of researchers led by Dr. Hermann Heipieper (UFZ, Leipzig) have shown that R. opacus PWD4 cells respond to toxic concentrations of salt and 4-chlorophenol by changing their mycolic acid composition. The study further demonstrates the relation between mycolic acid and phospholipid synthesis and their contribution to the surface properties of these cells. Click on title to learn more.
Researchers at INESC MN and BERG-iBB recently published the development of a microfluidic device to simultaneously screen a panel of toxins in multiple samples. This interdisciplinary work combines biochemistry, physics and materials engineering to (1) generate a reproducible array of 9 discrete immunosensing regions in an area of 0.12 mm2, (2) achieve the required sensitivities and (3) integrate an array of microfabricated Si photoconductors to acquire the signal of each discrete region. This type of device holds promise towards the rapid screening of key harmful mycotoxins in foods and feeds, assuring an effective enforcement of EU regulations. Click on title to learn more.
Multimodal chromatography is based on the use of synthetic ligands that provide more than one type of interaction with target analytes in a mobile phase. This technique has been showing a great potential for the purification of different biopharmaceuticals within complex biological mixtures, particularly monoclonal antibodies (mAbs). However, multimodal chromatography requires extensive optimization in a case-by-case basis to address specific purification problems. In a recent publication in the prestigious journal Analytical Chemisrty, researchers from BERG-IBB and INESC-MN led by Ana Azevedo and João Pedro Conde, developed a microfluidic platform to expedite optimization of adsorption and elution conditions of mAbs to a multimodal ligand using low amounts of reagent in a rapid and simple manner. Click on title to learn more.
Description: Culture of hiPSC-derived astrocytes (green) and neurons (red), featured photo by Cláudia Miranda, Copyright BERG-iBB 2016.
Context: BERG researchers led by Joaquim Cabral, Margarida Diogo and Tiago Fernandes are developing new methodologies for neural differentiation of human induced pluripotent stem cells (hiPSC). The work is being performed in the context of iBB’s Strategic Area 1: Stem Cell Engineering.
To mark the 6th Conference on Physiology of Yeasts and Filamentous Fungi, PYFF6, some of the best representative papers from two FEMS journals (FEMS Yeast Research and FEMS Microbiology Letters) were collected in a joint virtual issue edited by Professor Isabel Sá-Correia from the BSRG-iBB who chaired the Organizing and Scientific Committees of the Conference. Click on title to access the joint virtual issue for free.
Photo: Microsporum gypseum, CDC/ Dr. Lucille K. Georg, 1964.
Rejection and colonization by microbes are two problematic issues that often require the surgical removal of medical implants with increased risks for patients. In a recent publication in J. Materials Chemistry B, a team of researchers from iBB-BSRG (Nuno Mira, Diana Cunha), IST and Instituto Politécnico de Setúbal have shown that functionalization of Zn surfaces with ZnO-nanostructured 'Anastacia' flowers (NAF) results in improved biomaterials that can potentially overcome these important drawbacks and further boost the use of Zn in biomedical implants. Colonization of the NAF-coated Zn surface by Candida parapsilosis and Candida albicans, two of the more relevant microbial species colonizing medical devices, was significantly reduced on the NAF-coated Zn surface. The ZnO-derived coating is an expeditious strategy to improve the resilience of Zn-based resorbable biomaterials towards Candida spp. colonization, paving the way for the design of bioactive ZnO-derived coatings with potential for clinical applications on bone. Click on title to learn more.
Challenge: Can we improve the performance of biotechnological processes, food preservation and crop protection actions and the control of drug resistance and microbial pathogenicity by uncovering the complexity of cellular responses to new situations (e.g. stress)?
Strategic goal: Understand the complexity of cellular responses to environmental alterations and insults in order to improve biotechnological processes and applications and the efficacy of drugs and pesticides.
Challenge: Can we solve current industrial bottlenecks associated with biologically based manufacturing and develop new bioprocess engineering methodologies to translate scientific developments into new products and processes?
Strategic Goal: Design and develop the tools, technologies and materials required to support the biologically based manufacturing of the future.
The mini-symposium Rede AGRO “Dos vinhos de excelência aos produtos químicos: impacto da investigação em leveduras numa economia baseada na biotecnologia” will be held on July 14, at 4 p.m. This mini-symposium will take place at the rectory of Universidade de Lisboa (ULisboa), and follows the PYFF6 – 6th Conference on Physiology of Yeast and Filamentous Fungi, organised by Instituto Superior Técnico (IST) from 11th to 14th July. The current challenges of wine and beer industries will be presented and discussed, as well as the production of biofuels and other chemical compounds made from oil, from renewable raw materials, aiming to a sustainable bio based economy.
Respiratory infections by bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among cystic fibrosis patients. In a paper recently published in AMB Express, Silvia A. Sousa and Jorge H. Leitão from BSRG-iBB, in collaboration with researchers from Helwan University (Cairo), and medical doctors from Hospitals Sta Maria and D. Estefânia (Lisbon), studied the B. cenocepacia protein BCAL2958, a member of the OmpA-like family of proteins, showing the presence of anti-BCAL2958 antibodies in sera from cystic fibrosis patients with a clinical record of respiratory infection by Bcc, and the ability of the purified protein to in vitro stimulate neutrophils. Results strongly suggest that the protein is a potential candidate for usage in preventive therapies of infections by Bcc.
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