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User talk:Kammerhofer Sylvia/My sandbox

TRANSMIT - TRANSlating the role of MITochondria in Tumorigenesis

‎

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 evidences place mitochondria as key actors in cancer metabolic restructuring, not only because these organelles have a crucial role in the energy and biosynthetic intermediates production but also because occurrence of mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA has been associated to 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.

Further, TRANSMIT fosters the communication of this emerging field to the patients and their families. To these aims, TRANSMIT will create a network of seven different countries, among which world-leading basic science and clinical centers of excellence, several industrial partners with up-to-date omics 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 into 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 proposal envisions 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.

Coordinator

Alma Mater Studiorum – Università di Bologna - IT

Submitted by Anna-Maria Porcelli and Serena Paterlini (University of Bologna)

List of Participants

TRANSMIT is a multi-partner project that intends to mobilize the critical mass of expertise, by linking partners from 7 different countries, among which world-leading basic science and clinical centers of excellence, 4 SMEs as full partners, as well as non-profit foundations with a long-lasting history of dealing with the societal consequences of cancer in patients and their families.

Partner organisations

Fondazione Umberto Veronesi - IT
Innova SRL - IT
CEUB Il Centro Residenziale Universitario di Bertinoro (Ce.U.B.) - IT
Dynamo Academy srl Impresa Sociale – IT

@@ Line 1: / Line 1: @@
-{{TRANSMIT page name}}
+{{Template:OROBOROS header page name}}
-:::: <big><big>TRANSlating the role of MITochondria in Tumorigenesis</big></big>
+:::: <big><big>TRANSMIT - TRANSlating the role of MITochondria in Tumorigenesis</big></big>
+[[Image:Horizon2020_logo_jpg.jpg‎|right|150px|Horizon 2020]]
-[[Image:Logo MitoFit-OROBOROS.jpg|right|300px|MitoFit]]
+‎
-'''Diagnosis of mitochondrial functions and mitochondrial injuries'''
-:::: Diagnosis of mitochondrial functions and mitochondrial injuries represents a current challenge for biomedical research and development. We address these challenges by introducing and extending the approach of '''[[cell ergometry]]''' as the state-of-the-art functional test of mitochondrial competence.  ''MitoFit'' establishes an inter-university Network in Mitochondrial Physiology and Comprehensive Exercise Testing, supporting translational research on mitochondrial competence in close collaboration with the local industry and other networks, e.g. Oncotyrol. '''''Mitochondrial fitness''''' will play an increasing role in therapeutic and preventive medicine, with exercise and caloric balance providing the most effective measures for the reduction of several age-related health risks and degenerative diseases. MitoFit is a gateway and milestone to better diagnose, support and treat patients in our modern, rapidly ageing society.
-::::» [[K-Regio MitoFit |K-Regio project MitoFit]]
+[[Image:European_commission_logo.png‎|right|150px|European commission]]
-::::» [[OROBOROS MitoFit Laboratory]]
+'''Cancer is not only a genetic, but also a metabolic disease'''
-::::» [[MitoFit news]]
+:::: 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 evidences place mitochondria as key actors in cancer metabolic restructuring, not only because these organelles have a crucial role in the energy and biosynthetic intermediates production but also because occurrence of mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA has been associated to different types of cancer.
-== MitoFit - hot topics ==
+== Objectives ==
-::::» [[MitoFit Science Camp 2016 Kuehtai AT]]
-::::» [[MITOEAGLE |COST Action approved: MITOEAGLE]]
+:::: '''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.
-::::* MitoFit quality control - new on MitoPedia
+:::: Further, '''TRANSMIT fosters the communication''' of this emerging field to the patients and their families. To these aims, TRANSMIT will create a network of seven different countries, among which world-leading basic science and clinical centers of excellence, several industrial partners with up-to-date omics technologies, as well as non-profit foundations and associations who care for cancer patients.
-::::# [[MitoPedia: Sample preparations]]
-::::# [[MitoPedia: SUIT]]
-::::» [https://www.nia.nih.gov/research/blog/2015/12/making-molecular-map-exercise Making a molecular map of exercise - NIH Common Fund]
+:::: 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 into 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.
-== Concept ==
-:::: A physically active and nutritionally healthy life style induces regulatory mechanisms that maintain aerobic performance and support functional mitochondrial competence. Even in advancing age, exercise increases aerobic fitness and maintains muscle mitochondrial density above the sedentary benchmark, contributing to the high quality of life characteristic of alpine regions such as Tyrol. Functional mitochondrial competence and aerobic fitness reduce several age-related health risks, including cardiovascular and degenerative diseases, such as type 2 diabetes, neurodegenerative diseases (Alzheimer’s, Parkinson’s, Huntington’s), and several types of cancer. As a result of a sedentary life style and progression to obesity, the decline of muscle mitochondrial capacity may contribute to accelerated ageing processes and development of degenerative diseases. Diagnostic evaluation of '''functional mitochondrial competence''' requires '''scientific and technological mitochondrial competence'''. '''MitoFit fit&well''' will combine the specialized scientific focus on mitochondrial research and exercise testing with the expertise of local companies of world-wide leadership in this expanding field. Beyond the added value emanating from the combination and coordination of these diagnostic elements, the consortium will collaborate on the implementation of refined and novel diagnostic protocols as a milestone towards an internationally recognized centre of excellence, with an explicit focus on sport and clinical perspectives to address mitochondrial health and disease.
+:::: '''TRANSMIT key methodologies and key objectives'''
+::::The proposal envisions 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.
-=== Objectives ===
+:::: [[Image:TRANSMIT key methodologies and key objectives.jpg|750px|Key methodologies and key objectives]]
-:::: MitoFit combines the expertise of experienced partners in a unique corporate framework. MitoFit will establish a research and diagnostic laboratory network to form a '''Centre of Excellence in Mitochondrial Physiology, Pathology, Comprehensive Exercise Testing, and Genetic Fingerprinting'''. Diagnostic analyses include cardiopulmonary (VO2max; CPX) and metabolic (31P-NMR; Ergospect) exercise testing, evaluation of mitochondrial performance (high-resolution respirometry; OROBOROS INSTRUMENTS), and genetic screening (mtDNA haplotypes, relevant nuclear encoded genes). Refined state-of-the-art diagnostic protocols are extended and evaluated in a training programme under acute high-altitude hypoxia versus normoxic conditions with healthy control subjects. Exposure to acute hypoxia represents a typical condition for millions of individuals annually skiing or mountaineering in Austria and particularly in Tyrol. Comprehensive mitochondrial and exercise testing protocols will be developed and validated in these studies. Case studies will translate the scientific expertise into the clinical setting. As a result, MitoFit will offer and apply these diagnostic services for (i) monitoring of training programmes in competitive athletes, (ii) life style analyses of the general population, (iii) exercise interventions for preventive and therapeutic medicine, and (iv) clinical diagnosis of individual patients.
+== Coordinator ==
-=== Technological and scientific innovation ===
+:::: [http://www.unibo.it/en/ Alma Mater Studiorum – Università di Bologna] - IT
+:::: Submitted by Anna-Maria Porcelli and Serena Paterlini (University of Bologna)
-:::: Diagnosis of mitochondrial function has advanced to a new technological level by the introduction of high-resolution respirometry, and on a scientific level of innovation by multiple substrate-uncoupler-inhibitor titration protocols with permeabilized fibres from small muscle biopsies. Nevertheless, compared to the small needle biopsy, functional mt-diagnosis on far less invasive blood samples (thrombocytes) might provide a '''new perspective for large-scale screening''' of individual athletes, extended cohorts in clinical studies, and application for individual patients. Simultaneous measurement of mitochondrial respiration and additional parameters (mt-membrane potential by ion selective electrodes, hydrogen peroxide production by spectrofluorimetry coupled to the O2k) requires the development of new diagnostic protocols that can be applied to permeabilized muscle fibres and/or intact and permeabilized thrombocytes. Although conventional cardiopulmonary exercise testing (CPX) provides insights into the coupling of external to cellular respiration, it mirrors insufficiently the metabolic processes in the contracting and recovering muscle. Thus, combining CPX and techniques assessing bioenergetic processes in the working muscles will undoubtedly increase the conclusiveness of exercise testing in athletes and patients. These diagnostic MultiSensor protocols in combination with comprehensive exercise testing and genetic fingerprinting will generate an '''innovative repertoire of diagnostic tests''' that can be offered in the context of sports and mitochondrial diseases.
+== List of Participants ==
-== From ''MitoCom'' to '''MitoFit''' – 2020 m and above ==
-[[File:Lemawork Kuehtai-MitoFit.jpg |left|520px|Lemawork Katema training in Kuehtai]]
-:::: Join those who seek the special recreational and adventurous experience with physical exercise in the alps. Your exercise is the gateway to your mitochondrial fitness.
-:::: '''MitoFit''' evolves as a unique network of practitioners in the high-end sector of recreation, sport and protective medicine, in collaboration with experts on mitochondrial physiology and mitochondrial medicine.
+::::TRANSMIT is a multi-partner project that intends to mobilize the critical mass of expertise, by linking partners from 7 different countries, among which world-leading basic science and clinical centers of excellence, 4 SMEs as full partners, as well as non-profit foundations with a long-lasting history of dealing with the societal consequences of cancer in patients and their families.
-::::» [http://www.hoehentraining-kuehtai.at altitude training in Kuehtai - 2020 m and more].
+::::*	[http://www.unibo.it/en/ Alma Mater Studiorum – Università di Bologna] - IT
+::::*	[http://www.uclouvain.be/index.html/ Universite Catholique de Louvain] - BE
+::::*	[http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS/ OROBOROS INSTRUMENTS GmbH] - AT
+::::*	[https://www.uni-giessen.de/welcome/ Justus Liebig Universität Giessen] - DE
+::::*	[https://www.salk.at/ Gemeinnützige Salzburger Landeskliniken Betriebsgesellschaft]  - AT
+::::*	[http://ki.se/start/ Karolinska Institutet]  - SE
+::::*	[https://www.cam.ac.uk/ The Chancellor, Masters and Scholars of the University of Cambridge] - UK
+::::*	[http://www.adera.fr/ Association pour le développement de l'enseignement et des recherches aupres des universities et des enterprises d’aquitaine] - FR
+::::*	[http://www.biocrates.com/ Biocrates Life Sciences AG] - AT
+::::*	[http://www.avanticell.com/ AvantiCell Science Ltd] - UK
-:::: We all know that feeling of being well from head to toe – or from muscle to brain – up in the mountains. Scientists want to get to the basis of this wellbeing, to gain insights into invisible molecular functions:  is it caused by the ’good air‘ we breathe, even though air gets very thin high up in the Alps? How do the lungs, blood, heart, brain, arms and legs – all organs and all somatic cells – react to altitude and relaxation in nature, to challenges in sport or to a short period of life on a mountain pasture?
-:::: Mitochondria are responsible for the energy supply in human and animal tissues; this is [[cell ergometry]], cell respiration – mitochondrial oxygen consumption. With the [[Oxygraph-2k |OROBOROS O2k]], we determine energy turnover of carbohydrates and fatty acids and quantify the efficiency of mitochondria in maintaining the vital body functions. In order to determine cellular fitness, parameters for oxidative stress and stress resistance are measured along with mitochondrial oxygen consumption. Biomedical research all over the world applies this method for the diagnosis of mitochondrial competence, especially in sports medicine and gerontology. The O2k, developed by the company OROBOROS INSTRUMENTS, is the world-wide leading instrument for diagnosing the aerobic capacity of mitochondria with the help of small samples of tissue or blood. OROBOROS INSTRUMENTS is located in Innsbruck, Austria. In the Mitochondrial Research Laboratory, the company tests the newest developments and develops standard protocols in cell ergometry.
+[[Image:University_of_Bologna_logo.png‎|60px|University of Bologna]]
+[[Image:Universite_Catholique_de_Louvain_logo.jpg‎‎|80px|Universite Catholique de Louvain]]
+[[Image:Logo OROBOROS INSTRUMENTS.jpg|80px|link=http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS OROBOROS]]
+[[Image:Justus_Liebig_Universität_Giessen_logo.png‎‎‎|120px|Justus Liebig Universität Giessen]]
+[[Image:SALK_logo.png‎‎‎‎|140px|Salzburger Landeskliniken]]
+[[Image:Karolinska_Institutet_logo.jpg‎‎‎‎‎|140px|Karolinska Institutet]]
+[[Image:Adera_logo.png‎|110px|Adera]]
+[[Image:Biocrates_logo.png‎‎|130px|Biocrates Life Sciences AG]]
+[[Image:AvantiCell_Science_logo.png‎‎‎|130px|AvantiCell Science Ltd]]
+[[Image:University_of_Cambridge_logo.png‎‎‎‎‎‎|220px|University of Cambridge]]
+== Partner organisations ==
-[[Image:MitoCom Tyrol.jpg|left|80px|link=MitoCom O2k-Fluorometer|MitoCom]]
+::::*	[http://www.fondazioneveronesi.it/ Fondazione Umberto Veronesi] - IT
-:::: The logo of ''MitoCom Tyrol'' (now transformed to MitoFit) is based on ''MiPArt'' by [http://www.mipart.at/?Odra-Noel Odra Noel]. ''Further details:'' »[[MitoCom O2k-Fluorometer]].
+::::*	[http://www.innovasrl.net/ Innova SRL] - IT
+::::*	[http://www.ceub.it/ CEUB Il Centro Residenziale Universitario di Bertinoro (Ce.U.B.)] - IT
+::::*	[http://www.dynamoacademy.org/ Dynamo Academy srl Impresa Sociale] – IT
-[[Image:MitoCom-Kuehtai 3453-web.jpg|430px|link=MitoCom O2k-Fluorometer|MitoCom Tyrol]]
+[[Image:Fondazione_Umberto_Veronesi.png‎‎|110px|Fondazione Umberto Veronesi]]
+[[Image:Innova_srl.jpg‎ |150px|Innova srl]]
+[[Image:Centro_Residenziale_Universitario.png‎ |90px|Centro Residenziale Universitario die Bertinoro]]
-=== Impact on life style: Tyrol – a heart for sport ===
+[[Image:Dynamo_Academy.png‎|90px|Dynamo Academy]]
-:::: Mitochondrial knowledge will, with its innovative approach, arouse a new awareness of preventive medicine, to which a physically active and calorie-balanced lifestyle can contribute significantly. Of particular importance is “healthy aging”, a generally improved quality of life and a reduced risk of a multiplicity of degenerative diseases influenced by the mitochondria: e.g. obesity, diabetes 2, various forms of cancer and dementias. Mitochondrial competence will be made a reality to a larger proportion of the population and the regional identity strengthened both amongst our own population and amongst tourists through the offer of exercise-orientated leisure packages in the Alpine landscape of Tyrol.
-[[File:MitoFit-protective medicine.jpg|700px|right|Instrumental innovation and interdisciplinary cooperation in mitochondrial physiology lead to new perspectives of functional mitochondrial diagnosis. Check your mitochondrial health is conveyed to the public as a keyword for taking care of a physically active life style as an invaluable component of preventive and therapeutic medicine.]]
-:::: Linkages are being created by '''MitoFit''' between research and clinical/practical needs with regard to the very recently established Olympic centre at the Institute of Sport Science of the LFU in Innsbruck and the Altitude Training Centre in Kühtai near Innsbruck leading to optimization of diagnostic exercise testing and training strategies. Importantly, this project seeks to promote research on exercise effects at moderate altitude. Tyrol represents a unique location which is visited by several millions of skiers and mountaineers, annually. On the one hand, regular physical activity and probably also exposures to moderate altitudes up to about 2500 m may contribute to well-being and longevity. On the other hand, however, unaccustomed exercise and acute altitude exposure may trigger serious cardiovascular adverse events in subjects at risk. This initiative should contribute to a better understanding of mechanisms responsible for beneficial and adverse effects supporting the development of appropriate preventive measures.
-:::: Appreciation by politicians and communication with an aspirational general public are essential to benefit from world-class research, for comprehensive mitochondrial and exercise testing and implementation of exercise as a medicine, and the development of a scientific foundation that may allow us to translate the complex diagnostic results into a patient-related mitochondrial score. The MitoFit network will emphasize the connections to international mitochondrial networks, for exchange of expertise and standardization of diagnostic approaches, in a joint effort to helping mitochondrial patients, preventing numerous diseases and making a difference to society.
-[[Image:MitoFit.jpg|left|60px|link=http://www.mitofit.org/index.php/K-Regio MitoFit|K-Regio MitoFit]]
-'''See also'''
-:::* '''[[K-Regio MitoFit]]''' is the next step following the K-Regio project ''MitoCom'' (mitochondrial competence; [[MitoCom_O2k-Fluorometer|O2k-Fluorometer]]), extending our world-wide technological leadership in mitochondrial respirometry with the development of a quality control system, MitoFit-Knowledge Management Platform and applications in preventive medicine (K-Regio project MitoFit).
-:::* Health tourism: http://www.tt.com/wirtschaft/7750785-91/mehr-gesundheit-f%C3%BCr-tirol-urlauber.csp
-:::* [http://www.uibk.ac.at/ipoint/dossiers/forschung_im_fokus/983677.html Sport science in focus]