Download April 2015

Instituto de Biologia
Experimental
e Tecnológica
April 2015
VOLUME 3
ISSUE 1
SPECIAL POINTS
OF INTEREST:
 iNOVA4Health
IBET COORDINATES THE RECENTLY FUNDED
INOVA4HEALTH PROGRAM IN TRANSLATIONAL MEDICINE
Highlights
 Conclusion of the
EuBerry Project
 DSM & iBET
Collaboration
 Stem Cells for Clinical
Applications
 3D Models for PreClinical Assays
 CARDIOSTEM Project
INSIDE
THIS ISSUE:
1
Highlights
2
Internal Events
3
National Partnerships
4
International Partnerships
5
Research Highlights
8
New Projects
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 “prediscovery”, 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.
9
Honours & Awards
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 introducing precision medicine to the medical doctor students at NMS.
10
Besides coordinating iNOVA4Health, iBET participates in a second R&D unit - GreenIt - coordinated by
ITQB-UNL and dedicated to research in Plant Science.
Science & Society
Page 2
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
EVENTS WITH OUR PARTNERS
OUR
VISION:
PROVIDING
BIOTECH
SOLUTIONS
GLOBALLY
OUR
MISSION:
CREATING VALUE
FOR OUR
PARTNERS
LEVERAGING
SCIENTIFIC &
TECHNOLOGICAL
KNOWLEDGE IN
BIOLOGY AND
CHEMISTRY
OUR
VALUES:
AMBITION,
COMMITMENT,
INTEGRITY,
SEARCH FOR
KNOWLEDGE,
INNOVATION,
SERVICE
FRUIT LOGISTICA 2015 - BERLIM
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.
INTERNAL EVENTS
BIOTECHNOLOGY MASTER STUDENTS FROM
MOZAMBIQUE ON STUDY VISIT TO IBET
A delegation from 3rd
Master's
edition
in
Biotechnology from University
Eduardo Mondlane (CB-UEM),
visited iBET last December
with a mission to identify
opportunities
for
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
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.
Page 3
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
INTERNAL EVENTS
iBET HOSTED THE FINAL SEMINAR OF THE EUBERRY PROJECT
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 million). From Portugal, INIAV was involved in “Production technologies”,
while iBET evaluated the consumption of berries in Portugal and explored 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 metabolized. Some of these metabolites were identified and are currently under study. New projects were also briefly presented by iBET as the ongoing 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 importance of information transfer between researchers and fruit producers.
National
Patnerships
NATIONAL PARTNERSHIPS
IBET IS A
FOUNDING MEMBER
PINHEIRO BRAVO”
OF THE
“CENTRO
DE
COMPETÊNCIAS
DO
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.
Page 4
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
INTERNATIONAL PARTNERSHIPS
DSM NUTRITIONAL PRODUCTS
DSM AND IBET
JOIN EFFORTS IN
DEVELOPING
NEW NATURAL
COLORANTS
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.
FF GROUP & IBET
IBET TO DEVELOP
AN OPTIMIZED
PRODUCTION
PROCESS FOR A
FERMENTED
BAVERAGE
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.
“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
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iBET FACTS & FIGURES / VOL. 3 ISSUE 1
RESEARCH HIGHLIGHTS
STEM CELLS:
DEVELOPING INTEGRATED STRATEGIES FOR THE PURIFICATION OF
HUMAN STEM CELLS TOWARDS CLINICAL APPLICATIONS
Undifferentiated cells
that 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.
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, cardiovascular, 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 successfully 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, potency and viability.
Within the scope of two projects funded by Fundação para a Ciência e Tecnologia, iBET researchers 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 discontinuous) 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 expansion 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 successfully 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 human 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
Page 6
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
IBET RESEARCHERS MIMIC THE CELLULAR COMPLEXITY OF THE HUMAN
BRAIN IN IN VITRO MODELS FOR PRE-CLINICAL RESEARCH
Research
Highlights
Neurological disorders represent a significant economic and social burden on our society nowadays and current 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 dopaminergic 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 production 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.
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 dopaminergic neurons marker and βIII-tubulin as
neuronal marker (Gualda, Simão et al, 2015)
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.
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
Page 7
CAREMI PROJECT - REGENERATING THE INJURED HEART USING STEM CELLS
FIRST-IN-HUMAN CLINICAL TRIAL PHASE USING MULTIPOTENT CARDIAC CELLS
TO TREAT ACUTE MYOCARDIAL INFARCTION WAS COMPLETED WITH SUCCESS
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.
(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.
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.
Page 8
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
NEW RESEARCH PROJECT
Research
Projects
CARDIOSTEM— ENGINEERED CARDIAC TISSUES AND STEM CELLBASED 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 preclinical 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.
Two FCT Investigator Starting grants secured by iBET researchers
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.
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
Page 9
HONOURS AND AWARDS
RESEARCHERS FROM IMM, IBET, ITQB AND IGC WERE AWARDED THE 2014 PFIZER AWARD IN
CLINICAL RESEARCH
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.
SANTANDER TOTTA / NOVA UNIVERSITY OF LISBON AWARD DISTINGUISHES NMS|FCM
(CEDOC), iBET and ITQB COLLABORATIVE PROJECT
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
The winner of the 8th edition of the Prémio de Investigação factors, allowing for the first time the recreation in a laboratory
Colaborativa Santander Totta NOVA University of Lisbon (Life environment of the pathological aspects present in neural tissue
Sciences) was the collaborative project between Cláudia of Alzheimer's patients.
SCALE-UP & MANUFACTURING OF CELL-BASED THERAPIES BEST STUDENT POSTER
WAS AWARDED TO BÁRBARA CUNHA
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.
Page 10
Science &
Society
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
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.
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.
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
Page 11
Meetings &
Courses
Page 12
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
iBET FACTS & FIGURES / VOL. 3 ISSUE 1
Page 13
iBET’S MOST RECENT PUBLICATIONS
1. Almeida AM, Bassols A, Bendixen E, Bhide M, Ceciliani F, et 10. Queiroga CSF, Vercelli A, Vieira HLA (2015) Carbon monoxal. (2015) Animal board invited review: advances in proide and the CNS: challenges and achievements. British Jourteomics for animal and food sciences. Animal 9: 1-17.
nal of Pharmacology 172: 1533-1545.
2. Cunha B, Peixoto C, Silva MM, Carrondo MJT, Serra M, et al. 11. Santos JA, Carneiro MF, Alcoforado MJ, Leal S, Luz AL, et al.
(2015) Filtration methodologies for the clarification and
(2015) Calibration and multi-source consistency analysis of
concentration of human mesenchymal stem cells. Journal of
reconstructed precipitation series in Portugal since the early
Membrane Science 478: 117-129.
17th century. Holocene 25: 663-676.
3. Diniz MS, Salgado R, Pereira VJ, Carvalho G, Oehmen A, et 12. Seixas JD, Santos MFA, Mukhopadhyay A, Coelho AC, Reis
al. (2015) Ecotoxicity of ketoprofen, diclofenac, atenolol and
PM, et al. (2015) A contribution to the rational design of Ru
their photolysis byproducts in zebrafish (Danio rerio). Science
(CO)(3)Cl2L complexes for in vivo delivery of CO. Dalton
of the Total Environment 505: 282-289.
Transactions 44: 5058-5075.
4. Fernandes P, Almeida AI, Kremer EJ, Alves PM, Coroadinha 13. Silva S, Sepodes B, Rocha J, Direito R, Fernandes A, et al.
AS (2015) Canine helper-dependent vectors production:
(2015) Protective effects of hydroxytyrosol-supplemented
implications of Cre activity and co-infection on adenovirus
refined olive oil in animal models of acute inflammation and
propagation. Scientific Reports Mar 16;5:9135.
rheumatoid arthritis. The Journal of nutritional biochemistry
26: 360-368.
5. Fernandes P, Simao D, Guerreiro MR, Kremer EJ, Coroadinha AS, et al. (2015) Impact of adenovirus life cycle progres- 14. Simao D, Pinto C, Piersanti S, Weston A, Peddie CJ, et al.
sion on the generation of canine helper-dependent vectors.
(2015) Modeling Human Neural Functionality In Vitro: ThreeGene Therapy 22: 40-49.
Dimensional Culture for Dopaminergic Differentiation. Tissue
Engineering Part A 21: 654-668.
6. Fonseca C, Planchon S, Serra T, Chander S, Saibo NJM, et al.
(2015) In vitro culture may be the major contributing factor 15. Carmo CS, Nunes AN, Serra AT, Ferreira-Dias S, Nogueira I,
for transgenic versus nontransgenic proteomic plant differDuarte CMM. (2015) A way to prepare a liposoluble natural
ences. Proteomics 15: 124-134.
pink colourant. Green Chem.17:1510-18
iBET
Av. República,
Qta. do Marquês
Edificio IBET/ITQB
2780-157 Oeiras Portugal
Phone: +351 214421173
Fax: +351 214421161
E-mail: [email protected]
7. Gomes-Alves P, Serra M, Brito C, R-Borlado L, Lopez JA, et 16. Gonçalves, VSS, Rodríguez-Rojo, S, Matias, AA, Nunes,
al. (2015) Exploring analytical proteomics platforms toward
AVM, Nogueira, ID, Nunes D, Fortunato E, Alves de Matos
the definition of human cardiac stem cells receptome. ProAP, Cocero MJ, Duarte CMM. (2015) Development of
teomics 15: 1332-1337.
multicore hybrid particles for drug delivery through the
precipitation of CO2 saturated emulsions. International
8. Lamosa P, Lourenco EC, d'Avo F, Nobre A, Bandeiras TM, et
Journal of Pharmaceutics, 478 (1) 9-18
al. (2015) A unique glyceryl diglycoside identified in the
thermophilic, radiation-resistant bacterium Rubrobacter 17. Matias A, Nunes SL, Poejo J, Mecha E, Serra AT, Madeira PJ,
xylanophilus. Extremophiles 19: 373-382.
Bronze MR, Duarte CMM. (2015) Antioxidant and antiinflammatory activity of a flavonoid-rich concentrate
9. Mata AT, Ferreira JP, Oliveira BR, Batoreu MC, Crespo MTB,
recovered from Opuntia ficus-indica juice. Food Funct. 5 (12)
et al. (2015) Bottled water: Analysis of mycotoxins by LC-MS/
3269-80.
MS. Food Chemistry 176: 455-464.
iBET: GROWING IN COUNTERCURRENT
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.
VISIT US @
www.ibet.pt
EDITOR:
Gonçalo Real