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TRANSMIT : TRANSlating the role of MItochondria in Tumorigenesis
- TRANSMIT is a multi-partner project that intends to mobilize the critical mass of expertise, by linking beneficiaries from 7 different countries and partners from the social field. Beneficiaries are 7 world-leading basic science labs and 3 private SMEs.
- Cancer is not only a genetic, but also a metabolic disease.
- The consolidation of the knowledge that cancer is not only a genetic, but also a metabolic disease, has led scientists to investigate the intricate metabolic plasticity that transformed cells must undergo to survive the adverse tumor microenvironment conditions, and the contribution of oncogenes and tumor suppressors in shaping metabolism. In this scenario, genetic, biochemical and clinical evidence places mitochondria as key actors in cancer metabolic restructuring, not only because these organelles play a crucial role in energy production and formation of biosynthetic intermediates, but also because occurrence of mutations in both nuclear and mtDNA encoding metabolic enzymes is associated with different types of cancer.
- TRANSMIT aims to dissect the metabolic remodeling in human cancers, placing the focus on the role of mitochondria and bridging basic research to the improvement/development of therapeutic strategies.
- TRANSMIT fosters the communication of this emerging field to the patients and their families. Accordingly, TRANSMIT will create a network of seven countries, including world-leading basic science and clinical centers of excellence, several industrial partners with up-to-date technologies, as well as non-profit foundations and associations who care for cancer patients.
- By creating the critical mass of scientific excellence, TRANSMIT will allow to transfer the current knowledge into the wide field of cancer research, translating scientific and technical advances to the education and training of eleven Early Stage Researchers. TRANSMIT will implement training-through-research dedicated to unravel the metabolic features of cancer, as well as to provide a full portfolio of complementary skills through the creation of a network of basic, translational and industrial laboratories, devoted to a multidisciplinary/multisectorial education of young scientists.
- TRANSMIT key methodologies and key objectives: The project is structured in three scientific WPs. For each WP, several ESRs are recruited as indicated below the WP title. Scientific WPs share the key methodologies indicated within the four sectors of the romboid in light grey. The implementation of key methodologies in pairs allows the achievement of the key objectives indicated by the dark grey arrowheads.
- Duration of the project: 01.01.2017 - 31.12.2020
- TRANSMIT PhD student at Oroboros: Ana Bastos
Early Stage Researchers
ESR Name Consortium Member Country Scientist in charge Project title 1 Saharnaz Sarlak University of Bordeaux France Rodrigue Rossignol Bioenergetics of lung tumors 2 Ana Carolina Bastos Sant'Anna Silva Oroboros Instruments Austria Erich Gnaiger Cell ergometry and mitochondrial metabolic biomarkers in cancer 3 Floriana Jessica Di Paola Justus-Liebig-University of Giessen Germany Sybille Mazurek Coordination of glutaminolysis and glycolysis in cancer cells 4 Christina Schmidt University of Cambridge England Christian Frezza Fumarase and fumarate: epigenetic modifications in FH-deficient tumors 5 Nikkitha Umesh Ganesh University of Bologna, DIMEC Italy Giuseppe Gasparre Mitochondrial complex I-driven regulation of the hypoxic response in cancer cells 6 Nicole Bezuidenhout Karolinska Institute Sweden Maria Shoshan Roles of mitochondrial biogenesis enzymes in regulation of chemoresistance 7 Maheshwor Thapa Biocrates Life Sciences AG Austria Guido Dallmann Quantitative analysis of coenzymes in cancer cells 8 Ana Catarina da Silva Almeida AvantiCell Science Ltd Scotland Colin Wilde Cancer cell models to test metabolic intervention strategies 9 Houda Abla University of Bologna, FaBiT Italy Anna Maria Porcelli Inducing pseudonormoxia as adjuvant therapeutic strategy for cancer 10 Luca Zampieri Université catholique de Louvain Belgium Pierre Sonveaux Targeting mtROS to prevent cancer metastasis 11 Daniela Weber Paracelsus Medical University Austria Barbara Kofler Impact of ketogenic diet on tumor behavior
Representative of Assembly of ESRs (AEs)
The AEs is an important body within the TRANSMIT management structure. It is composed by all ESRs recruited, in which web meetings will be held as well as during end-year meetings and compulsory training activities.
Through the AEs, the ESRs have the opportunity to discuss about your research and training activities. The AEs meetings are coordinated by a representative elected every six months by his/her own peers, for a maximum of two mandates.
Tasks of the representative:
- Reports to the TRANSMIT Supervisory Board (SB) and to the Project Coordination Team (PCT) ideas, issues and suggestions of the Assembly.
- Agendas and decisions of AEs meetings is filed in minutes and posted on the intranet.
Tasks of the AEs:
- Organisation of end-year meetings.
- Annual report on: assessment of quality and state of training; personal/social situations of ESRs; proposals for activities of individual PCDPs; proposal for activities to enhance career development; troubleshooting.
TRANSMIT Marie Skłodowska-Curie PhD Fellowship with Oroboros Instruments / Medical University Innsbruck (WP1/ESR2)
- Cell ergometry and mitochondrial metabolic biomarkers in cancer
- Compared to normal cells, cancer cells have been shown to display a reprogrammed metabolism resulting from the specific energy demands imposed by growth factor signaling. Furthermore, in the case of metastatic cells, migration and colonization of distant tissues also contribute to the extra energy burden . In this regard, mitochondrial respiratory competence is retained with a shift towards biosynthetic functions, enabling cells to survive in an otherwise incompatible microenvironment and increasing the expression of key enzymes that affect the metabolic flux and proliferative pathways as well as genes involved in the acquisition of resistance to anoikis through suppression of apoptotic programs .
- Mitochondrial NADH-linked malic enzyme 2 (ME2) does not only play a key role in glutaminolysis, but its enforced expression suppresses senescence, whereas downregulation of ME2 modulates the outcome of p53 activation, leading to strong induction of senescence but not apoptosis . To assess regulatory roles, the development and application of new respiratory substrate-uncoupler-inhibitor-titration (SUIT) protocols are required due to its success in high-resolution respirometry (HRR) and cell ergometry (Pesta 2012 Methods Mol Biol). In addition, the improvement of the extension of HRR to MultiSensor analysis for simultaneous evaluation of several mitochondrial functions (e.g. mitochondrial membrane potential, reactive oxygen species production, proton flux in comparison to aerobic lactate production, Ca2+/ dependency) may contribute to the identification of mitochondrial metabolic biomarkers for characterizing the transformation from benign to cancer cells.
- In this PhD project, the development and testing of novel biomarkers protocols will be performed initially on prostate cancer cells, in comparison with metabolic remodeling of non-cancer epithelial cells. Furthermore, the extension of the study with proteomics and metabolite tracing may contribute as a powerful tool towards metabolic flux and bioenergetics. Also, detailed analysis of the mitochondrial respiratory complexes in prostate cancer cells versus non-cancer epithelial cells as well as metastatic cells.
-  P. S. Ward and C. B. Thompson, “Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate,” Cancer Cell, vol. 21, no. 3. pp. 297–308, 2012.
-  R. J. DeBerardinis, J. J. Lum, G. Hatzivassiliou, and C. B. Thompson, “The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation,” Cell Metabolism, vol. 7, no. 1. pp. 11–20, 2008.
-  P. Jiang, W. Du, A. Mancuso, K. E. Wellen, and X. Yang, “Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence,” Nature, vol. 493, no. 7434, pp. 689–693, 2013.
Bastos Sant'Anna Silva AC, MSc was sellected to a Marie Skłodowska-Curie PhD Fellowship and enrolled her PhD at the Medical University of Innsbruck on the 1st of October, 2017, being part of Oroboros Instruments, supervised by Erich Gnaiger.
Main objective: To identify mitochondrial metabolic biomarkers for characterizing the transformation from benign to cancer cells.
- University of Bordeaux (M25-M30, 6 months): To this aim she will extend her studies through proteomics and metabolite tracing, since these are powerful tools towards metabolic flux and bioenergetics.
- Supervision: Rodrigue Rossignol
- University of Bologna, (M35-M37, 3 months): Detailed analysis of the mitochondrial respiratory complexes in prostate cancer cells versus non-cancer epithelial cells as well as metastatic cells.
- Supervision: Anna Maria Porcelli
|TRANSMIT Kick-off meeting Bologna IT||2017-02-19|
|MiPNet22.07 IOC124 Schroecken AT||2017-10-03|
|MiPNet23.01 IOC126 Innsbruck AT||2018-01-24|
|DSL retreat Innsbruck AT||2018-02-15||Vill AT, 2018 Feb 15. Second retreat of the Daniel Swarovski Research Laboratory (DSL).|
|Life Sciences Meeting 2018 Innsbruck AT||2018-04-05||Innsbruck AT, 2018 Apr 05-06.13th Life Sciences Meeting.|
|Long Night of Research 2018 Innsbruck AT||2018-04-13|
|Abcam 2018 Cambridge UK||2018-06-25||Cambridge, UK, 2018 Jun 25-27. Cancer and Metabolism conference.|
|TRANSMIT Mid-Term Review Meeting Bologna IT||2018-11-28|
|Course in Cancer Metabolism Bologna IT||2018-11-29|
|MiPNet23.11 IOC137 Innsbruck AT||2018-12-10|
|DSL Retreat 2019 Innsbruck AT||2019-02-21||Vill AT, 2019 Feb 21. Third retreat of the Daniel Swarovski Research Laboratory (DSL).|
|METABO & Cancer 2019 Marseille FR||2019-04-01||Marseille FR, 2019 Apr 1-2. 3rd edition - Metabolism and Cancer Meeting|
|Life Science PhD Meeting 2019 Innsbruck AT||2019-04-25||Innsbruck AT, 2019 Apr 25-26. Life Science PhD Meeting.|
|Course in Science Communication and Dissemination for TRANSMIT 2019 Milan IT||2019-05-02|
|Course in Social Entrepreneurship for TRANSMIT 2019 Milan IT||2019-05-06|
|Course in Bio-statistics 2019 Bologna IT||2019-05-08|
|UNIBO Workshop 2019 Bologna IT||2019-05-13||Bologna, IT, 2019 May 13-15. Technical workshop in Genetic and bioenergetic analysis of mitochondrial DNA mutations.|
|6th International Conference on Tumor Microenvironment and Cellular Stress 2019 Crete GR||2019-09-23||Chania, Crete, GR, 2019 Sep 23-28. 6th International Conference on Tumor Microenvironment and Cellular Stress: Signaling, Metabolism, Imaging and Therapeutic Targets.|
- Oroboros project manager:
- Alma Mater Studiorum – Università di Bologna - IT (lead partner)
- Universite Catholique de Louvain - BE
- Oroboros Instruments GmbH - AT
- Justus Liebig Universität Giessen - DE
- Gemeinnützige Salzburger Landeskliniken Betriebsgesellschaft - AT
- Karolinska Institutet - SE
- The Chancellor, Masters and Scholars of the University of Cambridge - UK
- Association pour le développement de l'enseignement et des recherches aupres des universities et des enterprises d’aquitaine - FR
- Biocrates Life Sciences AG - AT
- AvantiCell Science Ltd - UK
Further partner organisations
- Official announcement of the Marie-Curie Skłodowska Action TRANSMIT: http://cordis.europa.eu/project/rcn/205395_en.html