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== TRANSMIT | == About TRANSMIT == | ||
[[Image:European_commission_logo.png|right|150px|European commission]] | |||
'''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. | |||
:::: | |||
:::: [[Image:TRANSMIT key methodologies and key objectives.jpg|750px|Key methodologies and key objectives]] | |||
::::* TRANSMIT website: [[www.transmit-project.eu]] | |||
:::: | |||
== TRANSMIT Marie Skłodowska-Curie PhD Fellowship with Oroboros Instruments / Medical University Innsbruck == | |||
'''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 [1]. 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 [2]. | |||
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 [3]. 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 FluoRespirometry (HRFR) and cell ergometry [4]. In addition, the improvement of the extension of HRFR 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. | |||
The aim of this PhD thesis is to identify mitochondrial metabolic biomarkers for characterizing the transformation from normal to malignant cells. At the end of year 1, the ESR will have gained satisfactory knowledge in overall prostate cancer metabolism, O2k-FluoRespirometry and protocol design. | |||
:: | [1] 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. | ||
[2] 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. | |||
[3] 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. | |||
[4] D. Pesta and E. Gnaiger, “High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle,” Methods Mol. Biol., vol. 810, pp. 25–58, 2012. | |||
Revision as of 13:02, 4 January 2018
TRANSMIT
- TRANSMIT - TRANSlating the role of MItochondria in Tumorigenesis
About TRANSMIT
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.
- TRANSMIT website: www.transmit-project.eu
TRANSMIT Marie Skłodowska-Curie PhD Fellowship with Oroboros Instruments / Medical University Innsbruck
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 [1]. 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 [2]. 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 [3]. 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 FluoRespirometry (HRFR) and cell ergometry [4]. In addition, the improvement of the extension of HRFR 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. The aim of this PhD thesis is to identify mitochondrial metabolic biomarkers for characterizing the transformation from normal to malignant cells. At the end of year 1, the ESR will have gained satisfactory knowledge in overall prostate cancer metabolism, O2k-FluoRespirometry and protocol design.
[1] 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. [2] 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. [3] 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. [4] D. Pesta and E. Gnaiger, “High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle,” Methods Mol. Biol., vol. 810, pp. 25–58, 2012.
Events
| When | Where | |
|---|---|---|
| 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). |
| 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 |
| Course in Science Communication and Dissemination for TRANSMIT 2019 Milan IT | 2019-05-02 | |
| European public and private opportunities for R&D, Innovation and Technology Transfer for TRANSMIT 2019 Rome 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. |
| TRANSMIT Symposium 2020 Brussels BE | 2020-01-17 | |
| The Minerva – Gentner Symposium on Cancer Immunometabolism 2020 Rehovot IL | 2020-09-12 | Rehovot , IL, 2020 Sep 12-14. The Minerva – Gentner Symposium on Cancer Immunometabolism 2020. |
| Long Night of Research 2020 Virtual Event | 2020-10-09 | |
| TRANSMIT Open Access Course Virtual 2020 | 2020-10-15 | Virtual, 2020 Oct 15. Open Access and Open Science |
| ISCaM 2020 Virtual Event | 2020-10-20 | Virtual Event, 2020 Oct 20-Nov 24. ISCaM2020 - 7th Annual Meeting. |
| TRANSMIT School 2021 Virtual | 2021-03-22 | |
| TRANSMIT final meeting 2021 Virtual | 2021-06-19 | |
Coordinator
- TRANSMIT project coordinator in Bologna:
- TRANSMIT project manager:
- TRANSMIT dissemination assistant:
- Oroboros project manager:
Project partners
- 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
