april 2015 volume 3 issue 1

The results of the recent evaluation of the national scientific research and technological development units are out and the R&D unit coordinated by iBET - iNOVA4Health - was classified as Excellent with a total budget of over 4M€ for the upcoming 3 years (approx. 8M€ for the entire program, lasting 6 years).

iNOVA4Health is a translational medicine programme organizing the efforts of biomedical researchers involved in the biological understanding of disease, lead compounds and biopharmaceuticals “pre-discovery”, technological scientists involved in “preclinical development”, and clinicians involved in “early clinical and first in man clinical trials” from institutions within the NOVA University of Lisbon. The programme will have a strong emphasis on developing novel therapies for unmet medical needs to promote healthy ageing and in targeting chronic diseases that are responsible for two thirds of deaths worldwide and a major burden on health care systems for the future.

The programme is managed by iBET which is essentially responsible for the “preclinical development”; CEDOC - Center for Chronic Diseases - NOVA Medical School (NMS) will bring in most of the medical basic research; the IPOLFG, Portuguese Oncology Institute, will be involved in clinical and translational research in Oncobiology; finally ITQB-UNL will cover chemical and biochemical discovery/synthesis. Clinicians from 10 Hospitals where the NOVA Medical School carries out its clinical teaching duties will be responsible for the final translational steps. Some of the biopharmaceuticals for the translational work (phase I/phase II clinical trials), in particular Advanced Therapy Medicinal Products (ATMP’s) may be manufactured at GenIbet Biopharmaceuticals, an iBET spin off producing under cGMP certification.

By partnering with international key players, iNOVA4health will gain in excellence and professionalism, better understanding and anticipating new areas of unmet research needs; this effort will also become a key instrument for leveraging Portuguese medicine and pharma activities into new heights and intro-ducing precision medicine to the medical doctor students at NMS.

Besides coordinating iNOVA4Health, iBET participates in a second R&D unit - GreenIt - coordinated by ITQB-UNL and dedicated to research in Plant Science.

April 2015

VOLUME 3

ISSUE 1

SPECIAL POINTS OF INTEREST: iNOVA4Health

Conclusion of the EuBerry Project

DSM & iBET Collaboration

Stem Cells for Clinical Applications

3D Models for Pre-Clinical Assays

CARDIOSTEM Project

INSIDE THIS ISSUE: 1 Highlights 2 Internal Events 3 National Partnerships 4 International Partnerships 5 Research Highlights 8 New Projects 9 Honours & Awards 10 Science & Society

Instituto de Biologia

Experimental

e Tecnológica

IBET COORDINATES THE RECENTLY FUNDED INOVA4HEALTH PROGRAM IN TRANSLATIONAL MEDICINE

Highlights

FRUIT LOGISTICA 2015 - BERLIM

EVENTS WITH OUR PARTNERS

iBET accompanied its partner Vitacress to Fruit

Logistica 2015 an event that took place last

February in Berlin. FRUIT LOGISTICA covers

every single sector of the fresh produce

business and provides a complete picture of

the latest innovations, products and services

at every link in the international supply chain.

In the year that Portugal was a partnering

country, 44 Portuguese companies were

represented from global players to small and

medium-sized companies and organizations.

iBET FACTS & FIGURES / VOL. 3 ISSUE 1

for mobility and placement of students, teachers and researchers from Mozambique. This visit was a chance for the students to see in first hand state of the art laboratories and research centers. The mission to Portugal, coordinated by Biotrop / HCT was carried out under the project Advanced Training of Human Resources in the area of Biotechnology Applied to Management and Biological Resources Monitoring, financed by IP CAMÕES - Institute for Cooperation and Language.

INTERNAL EVENTS

BIOTECHNOLOGY MASTER STUDENTS FROM

MOZAMBIQUE ON STUDY VISIT TO IBET

A delegation from 3rd Master ' s ed i t ion i n Biotechnology from University Eduardo Mondlane (CB-UEM), visited iBET last December with a mission to identify o p p o r t u n i t i e s f o r collaboration. At iBET, the students learned about our research in biotechnology applied to biopharmaceuticals and novel therapies and also to the agro-forestry area. According to its Director, Eduardo Mondlane University needs to train its human resources for teaching and research, to enhance the capacity to provide services as well as training in scientific and technological areas. Such initiatives create opportunities

Internal Events

OUR

MISSION:

CREATING VALUE

FOR OUR

PARTNERS

LEVERAGING

SCIENTIFIC &

TECHNOLOGICAL

KNOWLEDGE IN

BIOLOGY AND

CHEMISTRY

OUR

VISION:

PROVIDING

BIOTECH

SOLUTIONS

GLOBALLY

OUR

VALUES:

AMBITION,

COMMITMENT,

INTEGRITY,

SEARCH FOR

KNOWLEDGE,

INNOVATION,

SERVICE


NATIONAL PARTNERSHIPS

The main objective of the EUBerry project was to provide the necessary knowledge and tools to facilitate development of high quality, consumer-desirable fresh berry fruits of high nutritional quality optimal for human health at a competitive cost. A second objective was the development and validation of a set of tools to improve competitiveness of European berry production and consumer accessibility to berry fruits. The EUBerry platform was developed and validated by using strawberry, raspberry and blueberry as model crop species. Additionally, specific critical points related to the improvement of berry fruit quality and reduction of production costs were considered also for currants and blackberries. The team involved 10 European Institutions and 4 SMEs and was awarded €3 million by the European Commission (total budget 4 mil-lion). From Portugal, INIAV was involved in “Production technologies”, while iBET evaluated the consumption of berries in Portugal and ex-plored the bioactive potential of berries for human health. In this Seminar, some of the major results were presented both in the areas of berry technology production and in berry consumption impact in health. An intervention study carried out in humans, showed that the bioactive compounds present in berries are differentially absorbed and metabo-lized. Some of these metabolites were identified and are currently un-der study. New projects were also briefly presented by iBET as the ongo-ing bets for future applications of berry fruits for human health. The seminar attended by 150 participants from R&D institutions and

from the agro-food industry, concluded with a round table discussing

the future of berries in Portugal, from research to the field and the im-

portance of information transfer between researchers and fruit produc-

ers.

INTERNAL EVENTS

iBET HOSTED THE FINAL SEMINAR OF THE EUBERRY PROJECT

IBET IS A FOUNDING MEMBER OF THE “CENTRO DE COMPETÊNCIAS DO PINHEIRO BRAVO”

The protocol for the establishment of the “Centro de Competências do Pinheiro Bravo” (CCPB), was signed on the 27th February at the Ministério da Agricultura e do Mar, with the presence of the Minister Assunção Cristas and representatives of the 33 founding member Institutions, including iBET. Due to the high economic, social and environmental importance of maritime pine in Portugal, the CCPB aims at increasing the cooperation among the economic stakeholders, the scientific research centers and public administration, to find and implement solutions to address the main challenges and bottlenecks for the sustainability of the maritime pine cluster in Portugal.

National Patnerships

INTERNATIONAL PARTNERSHIPS

DSM NUTRITIONAL PRODUCTS


DSM Nutritional Products, a global leader in nutritional ingredients, hosted the second Innovation Partnering Conference, “Connecting Bright Innovations II” on the past 15-17 December 2014 in Kaiseraugst, Switzerland. The conference connected talented entrepreneurs, scientists and product developers with key DSM executives, and affirmed DSM’s commitment to partner with small businesses and to engage with innovators in nutrition and health. The conference included a half-day Learning Academy, designed to open a dialogue with attendees and share DSM’s collaborations and product innovations, and was followed by a 20 minute presentation from each invited institution. Each presenter was assigned a mentor from Nutrition Capital Network (NCN) and DSM to help develop their presentation prior to the conference. The Nutraceuticals & Delivery group´s presentation was very well received by all

members of the jury. Following this event, DSM Nutritional Products showed interest in

moving forward with the presented project which lies in the topic of natural colorants

and natural antioxidants. DSM and iBET are finalizing the last details towards signing

the collaboration protocol. The project aims at developing and optimizing an extraction

process for the recovery of a new and high-added value natural ingredient with

application in food, pharma or cosmetic industries and, besides DSM, also involves the

participation of the High-Pressure Process Engineering Group from the University of

Valladolid.

DSM AND IBET JOIN EFFORTS IN DEVELOPING NEW NATURAL COLORANTS

FF GROUP & IBET

iBET, through its Food & Health Unit, and GrupoFF - Angola have started a new collaboration aiming at optimizing the production process for a fermented beverage. The project which includes developmental work from lab to pilot scale and Technical and Economic Analysis, involves several groups at iBET namely the Microbiology group, the Nutraceuticals & Delivery group and the Membrane Processes group. This one year project is expected, at the end, to deliver a detailed description of the industrial process as well as product samples for sensory analysis and market research (the product will be produced under appropriate conditions to be considered suitable for human consumption). GrupoFF - Angola is part of the Efes & Costa Group, a multinational conglomerate with businesses in the areas of agroindustry, health and wellbeing, pharmaceuticals, oil and environment amongst others.

IBET TO DEVELOP AN OPTIMIZED PRODUCTION PROCESS FOR A FERMENTED BAVERAGE

“SINCE ITS INCEPTION, IBET HAS BEEN BUILT ON THE IDEA OF CREATING A FIRST GRADE

BIOTECHNOLOGY DEVELOPMENT CENTER WITH EXCELLENT CAPABILITIES, AND TO PROVIDE

SERVICES TO BOTH ACADEMIC AND INDUSTRIAL BIOPHARMA CLIENTS. IT’S SUCCESS OVER

THE YEARS HAS BEEN THE FRUIT OF COMBINING A VERY TALENTED SCIENTIFIC TRAINING

ORGANIZATION WITH A STRONG MINDSET IN RELEVANT INDUSTRIAL APPLICATIONS, THUS

PROVIDING THE BEST OF BOTH WORLDS.”

Luís Maranga, General Manager at Bristol-Myers-Squibb

STEM CELLS:

Undifferentiated cellsthat can differentiate into specialized cells. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. Adult stem cells are frequently used in medical therapies, for example in bone marrow transplantation. Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves for cell therapy applications.

RESEARCH HIGHLIGHTS

DEVELOPING INTEGRATED STRATEGIES FOR THE PURIFICATION OF HUMAN STEM CELLS TOWARDS CLINICAL APPLICATIONS

Given the particular immunomodulatory characteristics and the capacity to secrete bioactive molecules with anti-inflammatory and regenerative features, human mesenchymal stem cells (hMSC) have become key candidates for autologous and allogeneic therapies. Currently, over 400 clinical trials are taking place using hMSC for a variety of therapies, including bone/cartilage, car-diovascular, neurodegenerative and gastrointestinal diseases as well as in diabetes, and for the treatment of graft-versus-host disease. Since therapies require high doses (from 105 to 109 cells per patient), and given that these cells have a low abundance in vivo, methods that can success-fully expand hMSC are compulsory. Ultimately, the increase in cell numbers will also raise the harvest volumes depending on the therapy type (autologous or allogeneic). Large culture volumes will need to be concentrated and washed, in order to ensure the efficient removal of impurities (e.g. protein and DNA), without compromising the cells’ characteristics in terms of identity, po-tency and viability. Within the scope of two projects funded by Fundação para a Ciência e Tecnologia, iBET research-ers developed an integrated bioprocess for the expansion and purification of hMSC, which can enable the delivery of high numbers of pure cells at low volumes, for therapy applications. The work focused on implementing strategies that could enhance hMSC expansion and understand the impact that several process parameters of tangential flow filtration (e.g. membrane material and pore size, shear rate, permeate flux) and two operation modes (continuous and discontinu-ous) have on hMSC’s quality (i.e. cell morphology, viability, identity and potency) and recovery yield during the purification and concentration process. Furthermore, in collaboration with Asahi Kasei (Japan), Corning Inc. and Repligen Corporation, the researchers could increase cell expan-sion ratio, using a continuous perfusion operation mode, which led to a shift in cell metabolism, therefore increasing their growth capability. This process was then integrated with a tangential flow filtration system, which enabled the concentration and washing of hMSC. Cells could be suc-cessfully concentrated (20-fold), with high cell recovery (>80%) and viability (>95%) and more than 98% purity. Overall, an integrated process allowed for a shorter process time, recovering 70% of viable hMSC (> 95%), with no changes in terms of morphology, immunophenotype, proliferation capacity and multipotent differentiation potential. This newly described process will have applicability for both autologous and allogeneic therapies, fulfilling the particular needs for both scale-up and scale-out in the biomanufacturing workflow of cell-based therapies.

ORIGINAL ARTICLES

Journal of Biotechnology (2015), in press Exploring continuous and integrated strategies for the up- and downstream processing of hu-man mesenchymal stem cells Cunha B, Aguiar T, Silva MM, Silva R, Sousa MF, Peixoto C, Serra M, Carrondo MJT, Alves PM

Journal of Membrane Science (2015), 478: 117–129 Filtration methodologies for the clarification and concentration of human mesenchymal stem cells

Cunha B, Peixoto C, Silva MM, Carrondo MJT, Serra M, Alves PM



IBET RESEARCHERS MIMIC THE CELLULAR COMPLEXITY OF THE HUMAN

BRAIN IN IN VITRO MODELS FOR PRE-CLINICAL RESEARCH

Neurological disorders represent a significant economic and social burden on our society nowadays and cur-rent treatments do not stop disease progression. Advances in the study of mechanisms responsible for the onset and progression of human neurological disorders and development of novel therapeutic approaches have been hindered by the lack of adequate and predictable disease models. One of the focus of Advanced Cell Models Laboratory of the Animal Cell Technology Unit is to develop tri-dimensional (3D) in vitro models that, by better mimicking the cellular microenvironment of human brain, will facilitate the integration of data for brain research, pre-clinical drug screening and toxicology, contributing to the fast approval and release of new therapeutics into the market. Researchers used a culture strategy based on scalable stirred suspension culture systems to establish novel long-term human brain 3D cell models from stem cells. Within the scope of the European project BrainCAV, the team developed a model mimicking the midbrain, enriched in dopa-minergic neurons, which are the main cell type and region affected in Parkinson’s disease. With this model researchers were able to recapitulate in the lab important brain features as cell functionality, ECM composition and metabolic signature. In collaboration with the Portuguese pharmaceutical company Tecnimede Group, the focus has been on the efficient produc-tion of large numbers of human 3D neural models in which neurons and astrocytes are present to mimic the cellular complexity of human brain and attain higher relevance in drug screening campaigns. Moreover, an extensive toolbox of molecular and phenotypic analytical methodologies has been adapted to 3D neural cell models. In collaboration with IGC (Instituto Gulbenkian de Ciência), the potential of state-of-the-art light sheet fluorescence microscopy (LSFM) for imaging of human neurospheres was explored, opening the door to more challenging experiments involving drug testing as well as a better understanding of relevant biological processes in an environment closer to the human brain. Through the collaboration with Dr. Uwe Marx’s group from the Technische Universität of Berlin, the neurospheres developed at iBET were distributed into a multi-organ chip (MOC) platform and co-cultured with human artificial liver tissues, which will allow long-term cultures in miniaturized controlled environments for studies involving repeated dose toxicity testing and mimic compound metabolization and systemic toxicity. Overall, the 3D human neural cell models developed at iBET are enhancing the biological relevance of the in vitro models used in the preclinical stages of the drug discovery process and can contribute to gain new insights in neurological diseases onset and progression.

ORIGINAL ARTICLES

Frontiers in Cellular Neuroscience (2014), 8:221 Imaging of human differentiated 3D neural aggregates using light sheet fluorescence microscopy Gualda E., Simão D., Pinto C., Alves P.M., Brito C.

Journal of Biotechnology – 3D Cell Culture Special Issue (2015), in press A multi-organ chip co-culture of neurospheres and liver equivalents for long-term substance testing

Materne E.M., Ramme A.P., Terrasso A.P., Serra M., Alves P.M., Brito C., Sakharov D.A., Tonevitsky A.G., Lauster R., Marx U. Tissue Engineering – Part A (2015), 21:3-4:654-68 Modelling human neural functionality in vitro: 3D culture for dopaminergic differentiation

Simão D., Pinto C., Piersanti S., Weston A., Peddie C.J., Bastos A.E.P., Licursi V., Schwarz S.C., Collison L.M., Salinas S., Serra M., Teixeira A.P., Saggio I., Lima P.A., Kremer E.J., Schiavo G., Brito C., Alves P.M.

Journal of Biotechnology – 3D Cell Culture Special Issue (2015), in press Novel scalable 3D cell based-model for in vitro neurotoxicity testing: combining human differentiated neurospheres with gene expression and functional endpoints

Terrasso A.P., Pinto C., Serra M., Filipe A., Almeida S., Ferreiral A.L., Predroso P., Brito C., Alves P.M.

Caption: Neuronal aggregates. The image to the left shows a neurosfere by scanning EM. The image to the right results of the fusion of 8 stacks recorded by sheet fluorescence microscopy (LSFM) and shows tyrosine hydroxylase as dopa-minergic neurons marker and βIII-tubulin as neuronal marker (Gualda, Simão et al, 2015)

Research Highlights


(POLY)PHENOLS AS PROMISING CYTOPROTECTANTS AGAINST PARKINSON

A work developed through a collaboration between iBET, ITQB and IMM opened new insights into the potential of (poly)phenols in neurodegenerative diseases. The study, published in Human Molecular Genetics, focuses on the protection of plant (poly)phenol extracts on alpha-synuclein (aSyn) toxicity and aggregation, the main hallmark of Parkinson’s disease. Parkinson’s disease is the second most common age-related neurodegenerative disease, after Alzheimer’s disease. Despite intensive studies on the molecular basis of this disorder, we still lack a comprehensive understanding of the underlying mechanisms, compromising the development of effective therapeutic strategies. Parkinson’s disease is deeply associated with the misfolding and aggregation of alpha-synuclein (αSyn). Corema album (camarinheira) leaves were characterized for the first time,

a work developed in collaboration with the James Hutton Institute in UK. This Portuguese endemic species revealed great potential, its (poly)phenols protected cells from aSyn toxicity, reduced oxidative stress and aSyn aggregation. Interestingly, (poly)phenols promoted the clearance of aSyn through autophagy, one of the cell quality control systems. Moreover, (poly)phenols interacted with aSyn in vitro, reducing its fibrillization and promoting the formation of stable oligomeric species. Importantly, these oligomers are non toxic to human neuroglioma cells and evidence suggests that they are non-propagating oligomers.

CAREMI PROJECT - REGENERATING THE INJURED HEART USING STEM CELLS

Results from the first study to evaluate clinical use of multipotent cells isolated from donor hearts (multipotent cardiac cells, CMC) to treat acute myocardial infarction were recently presented. Launch of the second study phase has been announced by the coordinator of the CAREMI project (Cardio Repair European Multidisciplinary Initiative), Dr. Antonio Bernad (Centro Nacional de Biotecnología of the Consejo Superior de Investigaciones Científicas (CNB-CSIC). This new phase will add 49 patients to the six already treated, who to date have shown "no adverse effects". Acute myocardial infarction is one of the major challenges facing health care systems in developed countries. Although prompt, effective treatment has considerably reduced mortality, infarction is responsible for a large proportion of cases of chronic cardiac insufficiency. In the last five years, CAREMI has developed a new approach to limit tissue damage caused by infarction, based on the activation of the heart’s natural repair mechanisms in response to damage. The project, coordinated through the Centro Nacional de Investigaciones Cardiovasculares (CNIC), is funded by the European Commission. The developed product is allogeneic CMC, which are administered easily and safely via the intracoronary route. Using this scheme, the medical team has validated batches of CMC for use when they will be most therapeutically effective. Preclinical results indicate that CMC administration during the first week post-infarction, once the clinical situation has stabilized, promotes major cardiac regeneration. In parallel, the CAREMI consortium is developing complementary therapies that include generation of microparticles loaded with therapeutic molecules that can act on cardiac tissue. CAREMI comprises renowned specialists in various basic research, preclinical and medical disciplines. The biotechnology company Coretherapix (Madrid), promoted this initiative and leads the technical and logistic development of the clinical trial and preclinical evaluation. The Centro de Cirugía de Mínima Invasión Jesús Usón (Cáceres) developed validation procedures in large animals. Two Spanish companies, Vivotecnia (Madrid) and Farmacros (Albacete), collaborated in biosafety and biodistribution studies in distinct phases of the project, and a third, 3P Biopharmaceuticals (Pamplona), produced the clinical quality CMC. The CNIC/CNB research centers, together with iBET and Coretherapix, carried out exhaustive molecular and cellular characterization of the human CMC population, their response to various stimuli, as well as characterization of the equivalent mouse cell populations. Characterization of the potential immune response to administered CMC was conducted at the Saint Louis Hospital in Paris. iBET and Coretherapix are currently developing a new cell production platform, which will allow the boost required for a more advanced clinical stage.

FIRST-IN-HUMAN CLINICAL TRIAL PHASE USING MULTIPOTENT CARDIAC CELLS TO TREAT ACUTE MYOCARDIAL INFARCTION WAS COMPLETED WITH SUCCESS

ORIGINAL ARTICLE

Hum Mol Genet. (2014), 24(6):1717-32

(Poly)phenols protect from α-synucleintoxicity by reducing oxidative stress and promoting autophagy Macedo D, Tavares L, McDougall GJ, Vicente Miranda H, Stewart D, Ferreira RB, Tenreiro S, Outeiro TF, Santos CN.


NEW RESEARCH PROJECT

iBET has secured two positions in this competitive program for the recruitment of researchers to Portugal’s R&D centers. The scientists awarded FCT Investigator Starting grants at iBET in 2014 are: António Roldão (Animal Cell Technology Unit) and Ana Matias (Food & Health Unit). Established in 2012, the FCT Investigator Programme provides 5-year funding to both post-doctoral researchers who wish to make the transition to independent researchers (Starting Grant), already independent researchers, with a proven track record, who wish to consolidate their research skills and establish leadership in their research fields (Developmental Grant), and established independent researchers, with an outstanding curriculum and proof of leadership (Consolidation Grant). The main focus of A. Matias research will be the intensification of green solid-liquid adsorption processes for the concentration and separation/purification (downstream) of bioactive natural entities (e.g novel anti-inflammatory agents) from agri-food waste streams and by-products. These processes may be further integrated with other novel “greener” strategies and easier scalable for the industry. The main focus of A. Roldao research will be (1) the development of a “universal” Influenza vaccine based on VLPs and produced in the insect cell-baculovirus system that doesn’t require an annual update, annual production campaign or annual immunisation programme, and (2) the development

of a large-scale VLP-based production platform for seasonal Influenza vaccine capable of, in the event of a pandemic, manufacturing high quantities of vaccine. The technologies therein developed can be readily applied to the production of other added-value biologics.

Two FCT Investigator Starting grants secured by iBET researchers

CARDIOSTEM— ENGINEERED CARDIAC TISSUES AND STEM CELL-BASED THERAPIES FOR CARDIOVASCULAR APPLICATIONS

Human stem cells are an important source of cells for regenerative medicine applications, in particular for the treatment of cardiovascular diseases (CVDs), a group of disorders of the heart and blood vessels. CVDs are the number one cause of death and morbidity globally. Several clinical trials are currently running to investigate their therapeutic effects. In addition, human stem cells are also an important source of cardiac cells for therapeutic drug screening and cardiotoxicity assessment. However, the use of stem cells for both applications is still limited due to several reasons. In the case of regenerative medicine,

there is a need for the (i) development of integrated processes for the expansion of stem cells or their progenies under GMP and xeno-free conditions (a topic already addressed in this issue), (ii) the study of the paracrine activity of stem cells and their delivery in the heart following infarction and (iii) the study of cellular and noncellular therapies in pre-clinical models following EMA/FDA guidelines. Conversly, for drug testing, there is a need to generate an in vitro heart for cardiotoxicity assessment. CARDIOSTEM is a new research project won under the scope of the MIT Portugal Call for Research Proposal for Testbed Oriented Research that aims at creating a scientific and technological platform based on stem cells for either the treatment of cardiovascular diseases or screening/toxicology assessment of new drugs to target the cardiovascular system. To do so the project has been organized in two work packages combining stem cell biology, bioengineering, biomaterials and animal testing and integrating a multi-disciplinary team formed by academic and industrial teams and a hospital, which have already running collaborations for more than 5 years. Work package 1 will focus in the development of stem cell-based therapeutics for cardiac regeneration and will have the contribution of 3 main Portuguese research centers with expertise in stem cell bioengineering: Center for Neuroscience and Cell Biology from Coimbra University, Instituto Superior Técnico and iBET, 2 satellite Portuguese research centers with expertise in animal testing, two stem cell-based companies (Crioestaminal and Cell2B), one team from the Massachussets Institute of Technology (MIT, Karp/Langer Lab) and an independent non-academic organization (Hospital de Santa Marta). The main goal of this work package is to study the therapeutic potential of two cellular-based therapies and one non-cellular-based therapy in pre-clinical models according to EMA/FDA guidelines. The second work package will focus in the development of stem cell–based assays for drug screening and toxicity assessment and will have the contribution of two main Portuguese research centers (CNC, iBET) and two MIT teams (Karp/Langer Lab and Doug Lauffenburger lab). Finally, CARDIOSTEM will train a generation of researchers/entrepreneurs in Regenerative Medicine/Drug screening and will host six MIT-Portugal PhD projects during the execution of the project.

Research Projects


Scale-up and Manufacturing of Cell-Based Therapies IV best student poster prize was awarded to Bárbara Cunha, PhD student from the Animal Cell Technology Unit. The work entitled “Filtration methodologies for the concentration and washing of human mesenchymal stem cells” describes the development of a scalable integrated strategy for the concentration and washing of human mesenchymal stem cells (hMSC) using tangential flow filtration (TFF) technology, a process that opens new venues for autologous and allogenic stem cell based treatments (see also article on page 5). Scale-up and Manufacturing of Cell-Based Therapies IV was held from 19 to 22 of January at San Diego, California, USA. This conference series aims to continue to play a central role in defining and refining the engineering sciences of cell-based therapies. This year, it focused mainly on process development, scale-up, and manufacturing of cell-based therapies and brought academics, clinicians, industry leaders, and regulators from all over the world together to discuss the most critical scientific and engineering challenges in this field.

SCALE-UP & MANUFACTURING OF CELL-BASED THERAPIES BEST STUDENT POSTER WAS AWARDED TO BÁRBARA CUNHA

HONOURS AND AWARDS

Researchers from IMM, iBET, ITQB and IGC were awarded the 2014 Pfizer Award in Clinical research for their work on a potential novel therapeutic alternative for the treatment of T-cell acute lymphoblastic leukemia, a very frequent type of leukemia in children. The research, published in the journal Oncogene, studied the role of a protein (CHK1) in patients and concluded that it is over expressed and hyperctivated, thus enabling the viability and proliferation of tumor cells of this disease. The Pfizer Awards are the oldest distinction in biomedical research in Portugal and result of a partnership between Pfizer and the Society of Medical Sciences of Lisbon with the aim to encourage and develop scientific research, covering all branches of medicine human.

RESEARCHERS FROM IMM, IBET, ITQB AND IGC WERE AWARDED THE 2014 PFIZER AWARD IN

CLINICAL RESEARCH

SANTANDER TOTTA / NOVA UNIVERSITY OF LISBON AWARD DISTINGUISHES NMS|FCM

(CEDOC), iBET and ITQB COLLABORATIVE PROJECT

The winner of the 8th edition of the Prémio de Investigação Colaborativa Santander Totta NOVA University of Lisbon (Life Sciences) was the collaborative project between Cláudia

Almeida (CEDOC-NMS|FCM-NOVA) and Catarina Brito (iBET, ITQB) - “Recapitulating late-onset Alzheimer’s disease in a three dimensional human neural cell model”. The project aims to develop an experimental a 3D cellular model of Alzheimers disease that can be used to study the disease induction mechanism and also for future testing of novel personalized therapeutic strategies. iBET has been developing 3D cellular models in order to recapitulate in the lab characteristics of neural tissue in terms of structure and function and tissue environment. In this project, researchers will apply these strategies to stem cells previously modified by genetic factors to recapitulate Alzheimer’s disease. The hypothesis is that by generating 3D models using these cells, researchers will be able to enhance the appearance and accumulation of the cellular changes triggered by these genetic factors, allowing for the first time the recreation in a laboratory environment of the pathological aspects present in neural tissue of Alzheimer's patients.


World Biotech Tour - Science Festival at Pavilhão do Conhecimento

During the next three years, 12 science centres from all over the world are going to host the WORLD BIOTECH TOUR. The WBT showcases the role of science centers in bringing together key stakeholders to promote understanding of a relevant societal issue: biotechnology. By involving students, teachers, science center professionals, and the general public in hands-on activities and discussions about key issues pertaining to biotechnology, the WBT’s objective is to demonstrate the relevance, excitement, and wonder of biotechnology. iBET participated in the first, 2-day science festival hosted this April by the Pavilhão do Conhecimento showcasing the several areas of research to which the institute is devoted in a total of 6 booths. From funghi to animal cells and their role in our day to day life, passing through the crystalization of proteins and the extraction of bioactive ingredients from fruit peel, over 2000 enthusiasts interacted with our researchers during the Festival in what was a fulfiling experience of sharing and fun.

World Biotech Tour - Biotechnology Meeting

Researchers Célia Miguel (Forest Biotech Lab) and Nelson Saibo (GPlantS), from iBET and ITQB, participated in the public

event “Biotechnology Meeting” organized by Ciência Viva in Pavilhão do Conhecimento, which took place last 10th January. The participation in the parallel session “Biotechnology applied to agriculture and forest” aimed at presenting to high school students examples demonstrating the importance and impact of Plant Biotechnology. This meeting is part of a series of initiatives of the WORLD BIOTECH TOUR (see bellow), an international project gathering science centres from all over the world with the same purpose: to demonstrate the relevance, excitement and wonder of biotechnology. The project is coordinated by ASTC (Association of Science-Technology Centers), with support of Biogen Idec Foundation.

Science & Society

http://worldbiotechtour.org/home

http://www.astc.org/index.htm

http://www.biogenidec.com/about.aspx?ID=5468


Meetings & Courses

iBET Av. República,

Qta. do Marquês Edificio IBET/ITQB 2780-157 Oeiras -

Portugal

Phone: +351 214421173 Fax: +351 214421161

E-mail: [email protected]

iBET’S MOST RECENT PUBLICATIONS

1. Almeida AM, Bassols A, Bendixen E, Bhide M, Ceciliani F, et al. (2015) Animal board invited review: advances in pro-teomics for animal and food sciences. Animal 9: 1-17.

2. Cunha B, Peixoto C, Silva MM, Carrondo MJT, Serra M, et al. (2015) Filtration methodologies for the clarification and concentration of human mesenchymal stem cells. Journal of Membrane Science 478: 117-129.

3. Diniz MS, Salgado R, Pereira VJ, Carvalho G, Oehmen A, et al. (2015) Ecotoxicity of ketoprofen, diclofenac, atenolol and their photolysis byproducts in zebrafish (Danio rerio). Science of the Total Environment 505: 282-289.

4. Fernandes P, Almeida AI, Kremer EJ, Alves PM, Coroadinha AS (2015) Canine helper-dependent vectors production: implications of Cre activity and co-infection on adenovirus propagation. Scientific Reports Mar 16;5:9135.

5. Fernandes P, Simao D, Guerreiro MR, Kremer EJ, Coroad-inha AS, et al. (2015) Impact of adenovirus life cycle progres-sion on the generation of canine helper-dependent vectors. Gene Therapy 22: 40-49.

6. Fonseca C, Planchon S, Serra T, Chander S, Saibo NJM, et al. (2015) In vitro culture may be the major contributing factor for transgenic versus nontransgenic proteomic plant differ-ences. Proteomics 15: 124-134.

7. Gomes-Alves P, Serra M, Brito C, R-Borlado L, Lopez JA, et al. (2015) Exploring analytical proteomics platforms toward the definition of human cardiac stem cells receptome. Pro-teomics 15: 1332-1337.

8. Lamosa P, Lourenco EC, d'Avo F, Nobre A, Bandeiras TM, et al. (2015) A unique glyceryl diglycoside identified in the thermophilic, radiation-resistant bacterium Rubrobacter xylanophilus. Extremophiles 19: 373-382.

9. Mata AT, Ferreira JP, Oliveira BR, Batoreu MC, Crespo MTB, et al. (2015) Bottled water: Analysis of mycotoxins by LC-MS/MS. Food Chemistry 176: 455-464.

10. Queiroga CSF, Vercelli A, Vieira HLA (2015) Carbon monox-ide and the CNS: challenges and achievements. British Jour-nal of Pharmacology 172: 1533-1545.

11. Santos JA, Carneiro MF, Alcoforado MJ, Leal S, Luz AL, et al. (2015) Calibration and multi-source consistency analysis of reconstructed precipitation series in Portugal since the early 17th century. Holocene 25: 663-676.

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14. Simao D, Pinto C, Piersanti S, Weston A, Peddie CJ, et al. (2015) Modeling Human Neural Functionality In Vitro: Three-Dimensional Culture for Dopaminergic Differentiation. Tissue Engineering Part A 21: 654-668.

15. Carmo CS, Nunes AN, Serra AT, Ferreira-Dias S, Nogueira I, Duarte CMM. (2015) A way to prepare a liposoluble natural pink colourant. Green Chem.17:1510-18

16. Gonçalves, VSS, Rodríguez-Rojo, S, Matias, AA, Nunes, AVM, Nogueira, ID, Nunes D, Fortunato E, Alves de Matos AP, Cocero MJ, Duarte CMM. (2015) Development of multicore hybrid particles for drug delivery through the precipitation of CO2 saturated emulsions. International Journal of Pharmaceutics, 478 (1) 9-18

17. Matias A, Nunes SL, Poejo J, Mecha E, Serra AT, Madeira PJ, Bronze MR, Duarte CMM. (2015) Antioxidant and anti-inflammatory activity of a flavonoid-rich concentrate recovered from Opuntia ficus-indica juice. Food Funct. 5 (12) 3269-80.

EDITOR: Gonçalo Real

VISIT US @ www.ibet.pt


Initially with a strong link to the Portuguese industry, iBET has now become a reference in international research, development and innovation working in synergy with top names of the international pharmaceutical industry. iBET’s research has become so relevant and so competitive that it has made the institute one of the main exporters of Portuguese knowledge. The fact that more than 60 multinational corporations have entrusted their research to iBET attests to the success of business generated at the institute. The volume of such business has increased yearly and in such a way that iBET has been able to create a vast number of qualified jobs hence contributing positively to the National economy at a time when a high percentage of qualified workers are migrating due to the lack of opportunities in Portugal. iBET currently employs as permanent staff 20 PhDs holders and 26 skilled technicians (graduates and masters). This corresponds to a 50% and 15% increase in PhD and Technician appointments respectively this year alone, confirming the trend already observed in the past couple of years. Moreover, iBET also hosts over a dozen PhD holders associated with National and International funding programs (Fundação para a Ciência e Tecnologia Investigator Program and Marie Curie Actions), more than 20 post-docs and 60 research fellows (including PhD students) all of which contribute to iBET’s scientific critical mass. In sum, iBET’s growth whether it is in science driven outputs, in contracts with industrial partners, or in R&D projects has been a constant over the last 10 years, far and foremost due to its people, their enthusiasm, dedication and effort to make iBET a leading reference in the world.

iBET: GROWING IN COUNTERCURRENT

april 2015 volume 3 issue 1

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