TRANSMIT

TRANSMIT

TRANSMIT - TRANSlating the role of MItochondria in Tumorigenesis

‎

TRANSMIT Marie Skłodowska-Curie PhD Fellowship with Oroboros Instruments / Medical University Innsbruck

11 Phd student positions are open in the TRANSMIT project. Oroboros offers one PhD position in collaboration with the Medical University of Innsbruck
Find out more, see: TRANSMIT PhD position
Application deadline: May 15, 2017
Oroboros MitoFit_Laboratory
More open positions within the TRANSMIT project can be found here.
Website

WP1/ESR2: Cell ergometry and mitochondrial metabolic biomarkers in cancer

After a brief period of re-emergence of the Warburg effect in oncological research, the underlying concept has been shown to be ineffective for elucidating causal relationships between mitochondrial dysfunction and tumor progression. During metabolic re-programming in many cancers and actively dividing cells mitochondrial respiratory competence is retained with a shift towards biosynthetic functions (Tan AS et al. Cell Metab 21:81-94, 2015). Mitochondrial NADH-linked malic enzyme (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 (Jiang P, et al. Nature 493:689-93, 2013). Development, evaluation and application of new respiratory substrate-uncoupler-inhibitor-titration (SUIT) protocols are required to assess the role of ME2, which is allosterically controlled by fumarate, succinate and ATP, in mitochondrial respiratory control in cancer versus benign cells. SUIT protocols are a hallmark of the success of high-resolution respirometry and cell ergometry (Gnaiger E. 4th ed. Mitochondr Physiol Network 19.12, 2014; Pesta, D, Gnaiger E. Methods Mol Biol, 810:25-58, 2012). ESR2 will improve the extension of high-resolution respirometry 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). This approach will contribute to the identification of mitochondrial metabolic biomarkers for characterizing the transformation from benign to cancer cells. ESR2 will therefore develop and test such novel biomarker protocols initially on prostate cancer cells, in comparison with metabolic remodeling of non-cancer epithelial cells. One secondment will extend the study with proteomics and metabolite tracing. Another secondment will aim at a detailed analysis of the respiratory complexes in prostate cancer cells versus non-cancer epithelial cells.

Planned secondment: 1) CELLOMET (M25-M30, 6 months; analysis of proteomic and metabolomic profiles); 2) UNIBO (M35-M37, 3 months; analysis of respiratory complexes)

Spring school

At M29 (June 2019 and right after the compulsory course offered by Dynamo Academy in Italy), Oroboros will organize a Spring School entitled “The MitoFit Training Camp (MitoFit TC)” in Innsbruck (Austria) for all recruited fellows. The MitoFit Training Camp (MitoFit TC) will offer introductory and advanced lectures on experimental protocol design, development of standard operating procedures (SOPs), data analysis and reporting in mitochondrial bioenergetics and high-resolution respirometry. The MitoFit TC will provide a unique opportunity for networking with international experts in mitochondrial physiology and students. During five training days, the school will offer hands-on training in practical sessions with the O2k-Fluorometer, the state-of- the-art instrument for measuring mitochondrial respiration simultaneously with other parameters such as ROS production and mitochondrial membrane potential. The following topics will be covered specifically: laboratory standards for instrumental quality control: SOPs; reference sample for high-resolution respirometry – the MitoFit proficiency test; mitochondrial and cellular respiratory physiology; new challenges for high instrumental performance; mitochondrial respiratory coupling and substrate control. NADH and cytochrome redox states; measurement of mitochondrial membrane potential by TPP+, and fluorescent dyes; oxygen kinetics in transient states and steady-states; thermodynamic principles: flux-force relationships, power and efficiency; interpretation of diagnostic respiratory assays; comparative mitochondrial physiology: species, tissues and cell models.

Relevant publications

Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. Oroboros MiPNet Publications, Innsbruck: 80 pp. ISBN 978-3-9502399-8-0. »Bioblast link«
Jiang P, Du W, Mancuso A, Wellen KE, Yang X (2013) Reciprocal regulation of p53 and malic enzymes modulates metabolism and senescence. Nature 493:689-93. »Bioblast link«
Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopsies of human muscle. Methods Mol Biol 810:25-58. »Bioblast link«
Tan AS, Baty JW, Dong L, Bezawork-Geleta A, Endaya B, Goodwin J, Bajzikova M, Kovarova J, Peterka M, Yan B, Pesdar EA, Sobol M, Filimonenko A, Stuart S, Vondrusova M, Kluckova K, Sachaphibulkij K, Rohlena J, Hozak P, Truksa J, Eccles D, Haupt LM, Griffiths LR, Neuzil J, Berridge MV (2015) Mitochondrial genome acquisition restores respiratory function and tumorigenic potential of cancer cells without mitochondrial DNA. Cell Metab 21:81-94. »Bioblast link«

TRANSMIT Call H2020-MSCA-ITN-2016

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.

Objectives

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.

Events

	When	Where
TRANSMIT Kick-off meeting Bologna IT	2017-02-19	Bologna IT, 2017 Feb 19 - 20 TRANSMIT Kick-off meeting.
MiPNet22.07 IOC124 Schroecken AT	2017-10-03	Schroecken AT, 2017 Oct 03-08 Oroboros O2k-Workshop on high-resolution respirometry (HRR), IOC124.
MiPNet23.01 IOC126 Innsbruck AT	2018-01-24	Innsbruck AT, 2018 Jan 24-26. Oroboros advanced O2k-Workshop on mt-membrane potential: TPP+ and fluorescent dyes. IOC126.
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	Innsbruck AT, 2018 Apr 13. Oroboros at Long Night of Research, CCB. The diagnostic bioenergetic report – a milestone on the way to mitochondrial fitness and physical well-being.
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	Bologna, IT, 2018 Nov 28. TRANSMIT Mid-Term Review Meeting.
Course in Cancer Metabolism Bologna IT	2018-11-29	Bologna, IT, 2018 Nov 29-30. Course in Cancer Metabolism.
MiPNet23.11 IOC137 Innsbruck AT	2018-12-10	Innsbruck AT, 2018 Dec 10-12. MitoFit Coaching Days - Basic IOC137.
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
European public and private opportunities for R&D, Innovation and Technology Transfer for TRANSMIT 2019 Rome IT	2019-05-02	Rome, IT, 2019 September 30 - October 3. European public and private opportunities for R&D, Innovation and Technology Transfer for TRANSMIT.
Course in Science Communication and Dissemination for TRANSMIT 2019 Milan IT	2019-05-02	Milan, IT, 2019 May 2-4. Course in Science Communication and Dissemination for TRANSMIT.
Course in Social Entrepreneurship for TRANSMIT 2019 Milan IT	2019-05-06	Milan, IT, 2019 May 6-7. Dynamo Academy Social Entrepreneurship and managerial skills course for TRANSMIT.
Course in Bio-statistics 2019 Bologna IT	2019-05-08	Bologna, IT, 2019 May 8-9. Course in Bio-statistics.
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	Brussels, BE, 2020 Jan 17-18. TRANSMIT Symposium - Fostering applicative discoveries in cancer metabolism
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	Virtual Event, 2020 Oct 09. Oroboros at Long Night of Research, CCB. The diagnostic bioenergetic report – a milestone on the way to mitochondrial fitness and physical well-being.
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	Virtual Event, 2021 Mar 22-23 TRANSMIT School on respirometry and experimental protocol design, particularly related to cancer research.
TRANSMIT final meeting 2021 Virtual	2021-06-19	Virtual, 2021 Jun 19. TRANSMIT final meeting.