Risultati finali
A systematic methodology will be investigated for reverse engineering: model selection and parameter identification using systematic model-based techniques. Validation studies
Researchers declaration of conformityResearchers declaration of conformity will be submitted on-line to the portal
Integrated experimental-modeling platform to tailor treatments in a patient-specificAn Integrated experimental-modeling platform will be developed to tailor treatments in a patient-specific and leukemia-specific chemotherapy schedule
Multi-scale models to capture heterogeneity in biological systemsNew multi-scale population balance models to capture heterogeneity in biological systems
Methodology for global dynamic optimization of cellular processesA new methodology for global dynamic optimization of cellular processes will be investigated. The methodology will be validated in several problems in collaboration with the partners..
Model-based dynamic optimization methods to explain (a posteriori use) or predictOptimal control formulations will be developed (using a mixed-integer dynamic optimization framework) to explain (a posteriori use) or predict (a priori use) the operating principles in metabolic and signaling pathways
Public dissemination of project resultsIn order to ensure that the project results are efficiently disseminated to scientific and industrial communities, the partners will implement specific measures. A dedicated work package has been defined to ensure the implementation of these measures as well as effective knowledge transfer among the partners. The partners will disseminate information about the goals of the project, ongoing activities, progress, results and the potential benefits and opportunities for Academia and the private sector. As first measure, the partners will use their own academic and industrial networks for dissemination. In addition, it is expected that at least 30 scientific papers (at least two per ESR), will be published in peer-reviewed journals. For each of the ESRs, one of the required publications will be submitted to a journal familiar to the biological systems engineering community (e.g. Biotechnology and Bioengineering, IEEE Transactions on Biomedical Engineering, Computers and Chemical Engineering, PLOS Computational Biology) and one publication will be submitted to a journal transcending the community (for more mathematical projects, relevant publications include: Journal of Global Optimization, INFORMS Journal of Computing, Optimization Methods and Software; for more biological projects, relevant publications include Proceedings of the National Academy of Sciences; Leukemia). Further dissemination activities will include: - Reporting software to facilitate exchange of data between the partners (Emdesk); - Presentations at scientific conferences; - Press-releases for the local and international media; - Organization of workshops with the participation of renowned scientists and external industrial leaders. The project partners will communicate and disseminate the results to several target sectors: scientific community (researchers and students), relevant industrial sectors, general public, potential investors/stakeholders. To ensure the access to the project results, all scientific publications will be made under the open-access concept – i.e. free of charge online access for the user. Both open access publishing and self-archiving options will be considered (also called ‚gold‛ or ‚green‛ open access model, respectively).
Development of an in silico leukemia modelA novel in silico leukemia model will be developed and solved using efficient computational; techniques.
Methodology for a more systematic model building, and subsequent modelA systematic methodology will be investigated for a more systematic model building, and subsequent model reduction for control and optimization purposes. Novel model-reduction techniques will be investigated and their accuracy will be assessed in example problems.
Kinetic model describing E.coli central metabolismA new kinet model describing E.coli central metabolism. The model will account for the underlying complexities and constraints
Methodology to model jointly signaling, regulatory and metabolic networksKinetic modeling of metabolic behavior including transcriptional regulation. The proposed modelling framework will integrate signal transduction, regulation and metabolism into dynamic mathematical models
Methodology to identify both structure and parameters of large signalling modelsA systematic methodology will be investigated to to identify both structure and parameters of large signalling models. Validation studies will be also performed.
Mathematical model-based strategy for the detection of drug targetsA novel mathematical model-based strategy will be investigated for the detection of drug targets
Final reportThe final report will be prepared and submitted according the contractual requirements and reporting rules.
Kinetic model of human metabolism derivedTo derive a new model of human metabolism. The model will account for uncertainty and incorporate stoichiometric, thermodynamic and physiological constraints
Mathematical model to describe regulation of metabolism by dynamic cellNew mathematical model to describe regulation of metabolism by dynamic cell signalling.
"Optimal operation profile capturing heterogeneity of ""high-fidelity"" bioprocess""To derive an optimal operation profile capturing heterogeneity of ""high-fidelity"" bioprocess models. A salient feature of the proposed approach is to develop model and techniques which are computationally tractable"
A SyMBioSys website will be set-up and maintained as an effective mean of communication between the participants and also for training and dissemination purposes.
Transferable skills coursesScientific publishing and dissemination.: Writing with a clear and direct style and plan, research, organize and compose a literature review; Practice skills on both sides of the camera and microphone, as well as gaining experience of effective scientific writing under real time pressure; Research Ethics, and Bioethics which will cover topics such as “The fabrication/falsification of Data”, “Professional and Personal Integrity”, “Plagiarism and Collusion”, and “Medical Research”; The relationship between communication, science and policymaking in both the developed and developing world. Entrepreneurship and IP management: Development of entrepreneurship skills including: idea generation; learning how to get investors excited; understanding marketing, design, and legal matters; Understanding of the technology behind the product. The students will have the opportunity to understand development processes and acquire project management skills. The students will also end up with an overview of White and Red Biotech market; Protection of intellectual property including: obtaining patents; licensing technology to established companies; copyrighting software; initiating start-ups
Doctoral degreesDoctoral degrees will be awarded to ESRs after succesfull completion of their Doctoral work.
SyMBioSys vacancies publishedVacancies will be published simultaneously through various media: European and world-wide read journals (e.g. Nature Jobs, jobs.ac.uk) for academic-related job adverts, the EU portal for jobs advert, the Commission’s own pages for the Marie Skłodowska-Curie Actions, SyMBioSys project website, beneficiaries’ graduate recruiting procedures, and informal approaches to colleagues both in academia and industry. The aim is to have a shortlist of candidates, with CVs and references available before the contracts are signed to ensure that prompt interviews would take place and researchers could be recruited on time.
Science-based coursesSelected Science-based courses include network-wide workshops and seminars to be attended by all recruited research. These includ: (i) Introduction to biological systems and bioprocesses model definition (ii) Fundamental Experimental Techniques for Biological Systems (iii) Kinetic model building in biological systems engineering (iv)Optimality principles in biological systems (v) Model-based metabolic engineering (vi) Informatics for Biological Systems
Conference organizationOrganization of an open conference on “Systematic Models for Biological Systems Engineering”
Pubblicazioni
Autori:
Sara Barbosa, Bastian Niebel, Sebastian Wolf, Klaus Mauch, Ralf Takors
Pubblicato in:
Biosystems, Numero 174, 2018, Pagina/e 37-48, ISSN 0303-2647
Editore:
Elsevier BV
DOI:
10.1016/j.biosystems.2018.10.008
Autori:
Jake Alan Pitt, Julio R. Banga
Pubblicato in:
BMC Bioinformatics, Numero 20/1, 2019, ISSN 1471-2105
Editore:
BioMed Central
DOI:
10.1186/s12859-019-2630-y
Autori:
Jake Alan Pitt, Lucian Gomoescu, Constantinos C. Pantelides, Benoît Chachuat, Julio R. Banga
Pubblicato in:
IFAC-PapersOnLine, Numero 51/19, 2018, Pagina/e 72-75, ISSN 2405-8963
Editore:
Elsevier
DOI:
10.1016/j.ifacol.2018.09.040
Autori:
Nikolaos Tsiantis, Eva Balsa-Canto, Julio R Banga
Pubblicato in:
Bioinformatics, Numero 34/14, 2018, Pagina/e 2433-2440, ISSN 1367-4803
Editore:
Oxford University Press
DOI:
10.1093/bioinformatics/bty139
Autori:
Chris Fotis, Asier Antoranz, Dimitris Hatziavramidis, Theodore Sakellaropoulos, Leonidas G. Alexopoulos
Pubblicato in:
Drug Discovery Today, Numero 23/3, 2018, Pagina/e 626-635, ISSN 1359-6446
Editore:
Elsevier BV
DOI:
10.1016/j.drudis.2017.12.001
Autori:
Michail E. Klontzas, Supachai Reakasame, Raquel Silva, Jose C.F. Morais, Spyros Vernardis, Robert J. MacFarlane, Manolis Heliotis, Eleftherios Tsiridis, Nicki Panoskaltsis, Aldo R. Boccaccini, Athanasios Mantalaris
Pubblicato in:
Acta Biomaterialia, Numero 88, 2019, Pagina/e 224-240, ISSN 1742-7061
Editore:
Elsevier BV
DOI:
10.1016/j.actbio.2019.02.017
Autori:
Osvaldo D. Kim, Miguel Rocha, Paulo Maia
Pubblicato in:
Frontiers in Microbiology, Numero 9, 2018, ISSN 1664-302X
Editore:
Frontiers Media
DOI:
10.3389/fmicb.2018.01690
Autori:
Alejandro F. Villaverde, Nikolaos Tsiantis, Julio R. Banga
Pubblicato in:
Journal of The Royal Society Interface, Numero 16/156, 2019, Pagina/e 20190043, ISSN 1742-5689
Editore:
The Royal Society
DOI:
10.1098/rsif.2019.0043
Autori:
Edoardo Gaude, Christina Schmidt, Payam A. Gammage, Aurelien Dugourd, Thomas Blacker, Sew Peak Chew, Julio Saez-Rodriguez, John S. O’Neill, Gyorgy Szabadkai, Michal Minczuk, Christian Frezza
Pubblicato in:
Molecular Cell, Numero 69/4, 2018, Pagina/e 581-593.e7, ISSN 1097-2765
Editore:
Cell Press
DOI:
10.1016/j.molcel.2018.01.034
Autori:
Alexander Schäfer, Enio Gjerga, Richard WD Welford, Imke Renz, Francois Lehembre, Peter MA Groenen, Julio Saez-Rodriguez, Ruedi Aebersold, Matthias Gstaiger
Pubblicato in:
Molecular Systems Biology, Numero 15/8, 2019, Pagina/e e8828, ISSN 1744-4292
Editore:
Nature Publishing Group
DOI:
10.15252/msb.20198828
Autori:
Romuald Győrgy, Michail E. Klontzas, Margaritis Kostoglou, Nicki Panoskaltsis, Athanasios Mantalaris, Michael C. Georgiadis
Pubblicato in:
Industrial & Engineering Chemistry Research, Numero 58/31, 2019, Pagina/e 13900-13909, ISSN 0888-5885
Editore:
American Chemical Society
DOI:
10.1021/acs.iecr.9b01988
Autori:
Romuald Győrgy, Michail E. Klontzas, Margaritis Kostoglou, Nicki Panoskaltsis, Michael C. Georgiadis, Athanasios Mantalaris
Pubblicato in:
IFAC-PapersOnLine, Numero 50/1, 2017, Pagina/e 9877-9882, ISSN 2405-8963
Editore:
Elsevier
DOI:
10.1016/j.ifacol.2017.08.1603
Autori:
Jan Rožanc, Theodore Sakellaropoulos, Asier Antoranz, Cristiano Guttà, Biswajit Podder, Vesna Vetma, Nicole Rufo, Patrizia Agostinis, Vaia Pliaka, Thomas Sauter, Dagmar Kulms, Markus Rehm, Leonidas G. Alexopoulos
Pubblicato in:
Cell Death & Differentiation, Numero 26/8, 2019, Pagina/e 1365-1378, ISSN 1350-9047
Editore:
Nature Publishing Group
DOI:
10.1038/s41418-018-0210-8
Autori:
Michail E. Klontzas, Spyros I. Vernardis, Manolis Heliotis, Eleftherios Tsiridis, Athanasios Mantalaris
Pubblicato in:
Stem Cells and Development, Numero 26/10, 2017, Pagina/e 723-733, ISSN 1547-3287
Editore:
Mary Ann Liebert Inc.
DOI:
10.1089/scd.2016.0315
Autori:
Asier Antoranz, Theodore Sakellaropoulos, Julio Saez-Rodriguez, Leonidas G. Alexopoulos
Pubblicato in:
Drug Discovery Today, Numero 22/8, 2017, Pagina/e 1209-1215, ISSN 1359-6446
Editore:
Elsevier BV
DOI:
10.1016/j.drudis.2017.04.013
Autori:
Rebekka K. Schneider, Ann Mullally, Aurelien Dugourd, Fabian Peisker, Remco Hoogenboezem, Paulina M.H. Van Strien, Eric M. Bindels, Dirk Heckl, Guntram Büsche, David Fleck, Gerhard Müller-Newen, Janewit Wongboonsin, Monica Ventura Ferreira, Victor G. Puelles, Julio Saez-Rodriguez, Benjamin L. Ebert, Benjamin D. Humphreys, Rafael Kramann
Pubblicato in:
Cell Stem Cell, Numero 20/6, 2017, Pagina/e 785-800.e8, ISSN 1934-5909
Editore:
Cell Press
DOI:
10.1016/j.stem.2017.03.008
Autori:
Romuald Győrgy, Michail E. Klontzas, Margaritis Kostoglou, Nicki Panoskaltsis, Athanasios Mantalaris, Michael C. Georgiadis
Pubblicato in:
27th European Symposium on Computer Aided Process Engineering, Numero 40, 2017, Pagina/e 2761-2766, ISBN 9780-444639653
Editore:
Elsevier
DOI:
10.1016/b978-0-444-63965-3.50462-1
Autori:
Bosisio, F.M., Antoranz, A., Bolognesi, M.M., Chinello, C., Wouters, J., Magni, F., Alexopoulos, L., Cattoretti, G. and van den Oord, J.
Pubblicato in:
bioRxiv, 2018
Editore:
Cold Spring Harbor Laboratory
Autori:
Tajti, F., Antoranz, A., Ibrahim, M.M., Kim, H., Ceccarelli, F., Kuppe, C., Alexopoulos, L.G., Kramann, R. and Saez-Rodriguez, J
Pubblicato in:
bioRxiv, 2019
Editore:
Cold Spring Harbor Laboratory
Autori:
Anika Liu, Panuwat Trairatphisan, Enio Gjerga, Athanasios Didangelos, Jonathan Barrat, Julio-Saez Rodriguez
Pubblicato in:
biorxiv, 2019
Editore:
Cold Spring Harbor Laboratory
DOI:
10.1101/541888
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