Difference between revisions of "TRACT"

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TRACT

TRACT - Training in Cancer Mechanisms and Therapeutics

TRACT: Call H2020-MSCA-ITN-2016

Marie Skłodowska-Curie Innovative Training Networks, Grant Agreement No. 721906
Duration: 48 months
Start: 2016-10-01
Web: TRACT Website and Twitter: TRACT_ITN

About TRACT

TRACT supports eleven PhD fellows to complete research projects in the three critical areas: biomarker discovery, molecular resistance mechanisms and metabolic transformation mechanisms. This will allow for the discovery of novel insights into the molecular and cellular basis of oral and oesophageal cancer and generate new diagnostic tools and therapeutics that will improve patient response and survival.

Aims

In 2012, 8.2 million people worldwide died of cancer, of which 5.3% or over half a million deaths were accounted for by oral and oesophageal cancer (OOC)

The European community requires early stage researchers (ESRs) trained in next-generation technologies for improved detection and treatment of oral and oesophageal cancers. The number of oral cancers diagnosed in the EU has increased by over 75% in the last 30 years, with long-term survival rates of only 50%. This is typically due to the late diagnosis of the disease and resistance to current therapies. Through the collaborative expertise of clinicians, biochemists, immunologists, and chemists TRACT will enable ESRs to discover novel insights into the molecular and cellular basis of these cancers and generate new diagnostic tools and therapeutics that improve patient response and survival. Each Institution brings unique but complementary expertise in cancer metabolism, metabolomics, high-resolution imaging, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development and translational medicine. Industrial placements in five European countries will ensure ESRs receive specialised training in the development of next-generation technologies in such areas as whole genome sequencing, CRISPR technology, drug screening, exosome isolation and analysis, cancer imaging, metabolism and metabolite analysis in addition to the unique employment experience of working in the private sector. Courses in commercialisation, project management and presentation skills will ensure ESRs will have the ability to present their results to the entire cross-section of the European community, through public engagement.

Objectives

TRACT provides ESRs with exposure to a collaborative network of European academic and industrial experts working in the complementary domains of cancer metabolism, metabolomics, high-resolution imaging, bioinformatics, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development, nanotechnology and translational medicine. Although there are many researchers working on OOC in the relevant domains listed above, there is a lack of integration between domains - through a programme of integrative training and research, TRACT will bring together relevant domains to deliver better diagnostics and therapeutics for OOC with the overall aim of improving patient response and survival.

TRACT delivers a cohort of internationally mobile cancer researchers with interdisciplinary skills who will have enhanced career prospects and be in a position to have an impact on the European and global research stage by providing new technologies that can drive entrepreneurship into the European economy and improved diagnostics and treatment options for cancer patients in Europe and beyond.

The overall aim of the research programme is to integrate basic and applied research in three related themes in order to deliver new diagnostic & prognostic tools and therapeutic approaches for patients with OOC.

During the project, TRACT ESRs undertake novel research to:

1) Determine novel biomarkers at the protein, glycan and molecular level to enable early detection of OOC and to predict patient response to therapy.

2) Uncover the molecular basis of drug resistance in OOC leading to the identification of new drug targets and the development of novel cancer therapeutics.

3) Enhance knowledge of metabolic transformation in OOC leading to the identification of novel targets for therapeutic intervention.

Coordinator

TRACT project manager: Catherine McPartlin - Trinity College Dublin - IE

TRACT project coordinator: Dr Daniela Zisterer - Trinity College Dublin - IE

Network

Project partners

Further partner organisations

Agilent Technologies - UK
Almac Diagnostics - UK
Andor Technology PLC - UK
Fraunhofer-Gesellschaft - DE
Horn international - Exosomics Siena S.p.A. - IT
National Institute for Bioprocessing Research and Training - IE
Opsona Therapeutics - IE

PhD Fellows and Supervisors

Total applications received for TRACT PhD Positions: 150

Countries represented: 44

Application profiles: 34% were EU, 4% are candidate EU countries and 62% are non-EU applicants.

Gender balance: 59% women, 41 % men.

11 appointed PhD students started in March 2017.

ESR	Project title	ESR name	Host institution	Supervisor(s)	Workpackage
1	Inflammatory response elements and glycan profiles as salivary biomarkers for the early diagnosis of OSCC	Valentina Dikova	UVEG (Valencia, Spain)	Prof. Jose Bagan	Biomarker Discovery (WP2)
2	Identification of novel molecular biomarkers predictive of benefit to neo-adjuvant chemotherapy in OAC	Eilis Sutton	QUB (Belfast, United Kingdom)	Dr. Richard Turkington & Prof. Richard Kennedy	Biomarker Discovery (WP2)
3	Modulation of salivary inflammatory markers in patients undergoing radiotherapy for OSCC	Sara Principe	UVEG (Valencia, Spain)	Prof. Jose Bagan	Biomarker Discovery (WP2)
4	A pathways-based approach to identify determinants of drug resistance in OAC	Niamh McCabe	QUB (Belfast, United Kingdom)	Dr. Richard Turkington & Prof. Richard Kennedy	Resistance Mechanisms (WP3)
5	Inflammatory caspases as biomarkers for OAC? Determining the role of inflammatory caspases in OAC development and resistance	Ewelina Flis	TCD (Dublin, Ireland)	Prof. Emma Creagh & Dr. James Murray	Resistance Mechanisms (WP3)
6	Mcl-1 inhibitors for the treatment of OSCC	Prashant Saraswati	UNISI (Siena, Italy)	Prof. Giuseppe Campiani & Stefania Butini	Resistance Mechanisms (WP3)
7	HAMLET derivatives as a pre-operative therapy in OAC	Magda Ghanim	TCD (Dublin, Ireland)	Prof. Ken Hun Mok & Dr. Vincent Kelly	Resistance Mechanisms (WP3)
8	Development of novel autophagy modulators to improve sensitivity of OSCC to chemotherapy	Tuhina Kahn	UNISI (Siena, Italy)	Prof. Giuseppe Campiani & Stefania Butini	Resistance Mechanisms (WP3)
9	Pre-clinical evaluation of targeting autophagy for the treatment of OSCC	Stefania Magnano	TCD (Dublin, Ireland)	Prof. Daniela Zisterer & Dr. Jeff O’Sullivan	Resistance Mechanisms (WP3)
10	Metabolic profiles in normal, dysplastic and cancerous oral cells	Enis Garipi	Oroboros Instruments (Innsbruck, Austria)	Prof. Erich Gnaiger	Metabolic Transformation (WP4)
11	Mitochondrial function linked to metabolic differences in normal, dysplastic and cancerous oral cells	Marilena Karavyraki	TCD (Dublin, Ireland)	Prof. Richard Porter	Metabolic Transformation (WP4)

Oroboros involvement

WP4: Metabolic transformation

High-resolution respirometry to assay real time bioenergetics and metabolism in oral cancer cells
Metabolic profiles of normal, dysplastic and cancerous oral cells
Comparison of oxygen consumption and extracellular proton flux, as metrics of metabolic flux in different cell types under normoxic and hypoxic conditions; correlate with chemotherapy sensitivity
Identify differential novel drug targets in the cancer cells

TRACT examines metabolic transformation mechanisms in OOC with the aim of identifying new drug targets for future therapeutic development. Metabolic transformation is a universal property of tumour formation and is a rich source of targets for development of therapeutic interventions. ESR 10 (Oroboros recruit; TCD secondment) will further characterise the bioenergetic and metabolic differences in normal, dysplastic and cancerous oral cancer cells using the Oroboros O2k-MultiSensor system. This approach will identify differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells. Factors that control mitochondrial dynamics in cancer cells have also emerged as possible therapeutic targets.

The dynamic structure of the mitochondria in mammalian cells is defined by the opposing forces of fission and fusion, but the regulation of these mitochondrial processes is poorly understood. This is an emerging area in cancer research where cutting-edge imaging technologies are merging with molecular and cellular biology techniques. Pilot studies performed by Porter in TCD have identified a key molecule involved in controlling mitochondrial abundance (namely SIRT3) as a determinant of drug resistance in some solid cancers. ESR 11 (TCD recruit; Oroboros secondment) will establish the relationship between mitochondrial abundance, morphology, functional proteins involved in mitochondrial dynamics and metabolic differences in normal, dysplastic and oral cancer cells. This new knowledge will lead to the identification of novel therapeutic targets.

Oroboros project manager: Mag. Verena Laner

TRACT PhD student (ESR10) at Oroboros Instruments / Medical University Innsbruck: Enis Garipi, MD - Metabolic profiles in normal, dysplastic and cancerous oral cells

Planned secondments: TCD (duration: 2x3 months, supervisor: Prof. Richard Porter) - measure metabolic flux through (a) glycolysis, (b) pentose phosphate pathway and (c) glutaminolysis using 2H/13C NMR.

Shao-Chiang Chang worked on this project successfully from 2017-Oct-01 to 2018-Jun-05.

Anja Bufe was selected as a PhD fellow and started her PhD project on 2017-03-01 with Oroboros Instruments at the Medical University of Innsbruck. Her appointmant ended prematurely on 2017-06-30.

TRACT Events

	When	Where
MiPNet22.03 IOC119 Innsbruck AT	2017-02-27	Innsbruck AT, 2017 Feb 28-Mar 03. MitoFit Coaching Days - Basic IOC119.
TRACT Kick-off meeting Dublin IE	2017-03-27	Dublin IE, 2017 Mar 27. TRACT Kick-off meeting.
MiPNet22.01 IOC122 Schroecken AT	2017-06-26	Schroecken AT, 2017 Jun 26-Jul 01 Oroboros O2k-Workshop on high-resolution respirometry (HRR), IOC122.
MiPschool Obergurgl 2017	2017-07-23	Obergurgl AT, 2017 Jul 23-30. 10^th MiPschool 2017 MitoEAGLE and MitoEAGLE Workshop WG1-4.
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.
MitoEAGLE Innsbruck 2018-01-29	2018-01-29	Innsbruck AT, 2018 Jan 29 - Feb 01. WG 4 blood cells workshop and retreat - COST Action MitoEAGLE.
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.
TRACT General assembly meeting Belfast UK	2018-04-16	Belfast UK, 2018 Apr 16. TRACT General Assembly meeting.
TRACT Training Belfast UK	2018-04-17	Belfast UK, 2018 Apr 17-19. TRACT training.
TRACT Mid-Term Review Meeting Dublin IE	2019-01-21	Dublin IE, 2019 Jan 21. TRACT Mid-Term Review Meeting.
TRACT Training 2019 Dublin IE	2019-01-22	Dublin IE, 2018 Jan 22-24. TRACT Training.
DSL Retreat 2019 Innsbruck AT	2019-02-21	Vill AT, 2019 Feb 21. Third retreat of the Daniel Swarovski Research Laboratory (DSL).

TRACT dissemination

Events

References

Schöpf B, Schäfer G, Weber A, Talasz H, Eder IE, Klocker H, Gnaiger E (2016) Oxidative phosphorylation and mitochondrial function differ between human prostate tissue and cultured cells. FEBS J. - »Bioblast link«
Makrecka-Kuka M, Krumschnabel G, Gnaiger E (2015) High-resolution respirometry for simultaneous measurement of oxygen and hydrogen peroxide fluxes in permeabilized cells, tissue homogenate and isolated mitochondria. Biomolecules 5:1319-38. - »Bioblast link«
Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E (2015) Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol 119:1210-8. - »Bioblast link«
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. - »Bioblast link«
Gnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. Scand J Med Sci Sports 25 (Suppl 4):126–34. - »Bioblast link«
Kristiansen G, Hu J, Wichmann D, Stiehl DP, Rose M, Gerhardt J, Bohnert A, ten Haaf A, Moch H, Raleigh J, Varia MA, Subarsky P, Scandurra FM, Gnaiger E, Gleixner E, Bicker A, Gassmann M, Hankeln T, Dahl E, Gorr TA (2011) Endogenous myoglobin in breast cancer is hypoxia-inducible by alternate transcription and functions to impair mitochondrial activity: a role in tumor suppression? J Biol Chem 286:43417-28. - »Bioblast link«
More than six

Support

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 721906

@@ Line 10: / Line 10: @@
 __TOC__
-== <big>Open PhD position at Oroboros Instruments in the Marie-Sklodlowska Curie Project TRACT  - deadline 2018 July 05</big> ==
-<br />
-:::: '''In the framework of the Marie Skłodowska-Curie action TRACT, Oroboros Instruments announces a vacant PhD position in cancer research with focus on mitochondrial function.'''
+== TRACT: Call H2020-MSCA-ITN-2016 ==
+::::* Marie Skłodowska-Curie Innovative Training Networks, Grant Agreement No. 721906
+::::* '''Duration''': 48 months
+::::* '''Start''': 2016-10-01
+::::* '''Web''': [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT Website] and [https://twitter.com/TRACT_ITN Twitter: TRACT_ITN]
-::::* '''Project background'''
-:::::: :[http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics '''TRACT'''] is an international, inter-sectoral, multi-disciplinary project providing Marie Skłodowska-Curie PhD Fellowships to early stage researchers (ESRs) with the potential to become the leaders of tomorrow in cancer research.
-:::::: TRACT is an international, inter-sectoral, multi-disciplinary project providing Marie Skłodowska-Curie PhD Fellowships to early stage researchers (ESRs) with the potential to become the leaders of tomorrow in cancer research. This project is funded by the European Union Horizon 2020 research & innovation programme under the Marie Skłodowska-Curie grant agreement No. 721906. TRACT enables ESRs to discover novel insights into the molecular and cellular basis of oral and oesophageal cancer and generate new diagnostic tools and therapeutics that will improve patient response and survival. ESRs trained through the TRACT network will be uniquely positioned for careers in academia, industry or as entrepreneurs.
+== About TRACT ==
-:::::: More information: [[TRACT]]
-::::* '''Criteria'''
+:::: '''TRACT''' supports eleven PhD fellows to complete research projects in the three critical areas: biomarker discovery, molecular resistance mechanisms and metabolic transformation mechanisms. This will allow for the discovery of novel insights into the molecular and cellular basis of oral and oesophageal cancer and generate new diagnostic tools and therapeutics that will improve patient response and survival.
-:::::: Applicants must hold the necessary qualifications entitling them to enroll in a PhD study in Austria: a MSc degree or equivalent, in natural sciences or related biomedical disciplines. You must be in the first four years of your career post primary degree, not yet holding a PhD degree. Relevant research experience is desirable. You are expected to possess a high standard of written and spoken English, with the following skills: team-player, self-organized, goal-oriented working style. Experience in methods of biochemistry, cell biology, bioenergetics and specifically in [[High-Resolution Respirometry |High-Resolution FluoRespirometry]] is of benefit.
-::::* '''Mobility'''
+=== Aims ===
-:::::: TRACT is a mobility-based EU project and ESRs are required to move country to commence their PhD training project. Applicants for this position must not have been resident in Austria for more than 12 months in the past 3 years.
-::::* '''Gross salary'''
-:::::: 35,476 EUR/year incl. mobility allowance, + 6,000 EUR/year family allowance, if applicable.
-::::* '''How to apply'''
-:::::: Please include a covering letter which specifies your reasons for applying and your suitability as a candidate, a copy of your CV which describes your relevant research training and experience and copies of your degree transcripts in English. Two independent letters of recommendation have to be provided. Send your application documents to [mailto:verena.laner@oroboros.at| verena.laner@oroboros.at]
-::::* <big>'''Application deadline: 2018 July 05.'''</big>
-=== Cancer metabolism ===
-::::* Intracellular pH plays a primary role in metabolic switching under anoxia (Hand and Gnaiger, 1988). In cancer metabolism, the importance of aerobic glycolysis and lactate accumulation is well established, and so is the pathophysiological relevance of hypoxia. Too little is known, however, about the '''effects of extracellular and intracellular pH on mitochondrial respiratory control'''. We have preliminary data that suggest opposite effects of pH on mitochondrial respiration in cancer versus benign cells, and the TRACT project should follow-up on this exciting topic.
-::::::::* Hand SC, Gnaiger E (1988) Anaerobic dormancy quantified in ''Artemia'' embryos: A calorimetric test of the control mechanism. Science 239:1425-7. - [[Hand 1988 Science |»Bioblast link«]]
-=== Unique research opportunities at Oroboros ===
-::::* We have two labs (Oroboros with '''17 O2k instruments''', and our lab at the Medical University with '''8 O2k instruments'''), all equipped with the newest '''[[O2k-FluoRespirometer |High-Resolution FluoRespirometry]]''' technology.
-::::* '''[[Oroboros MitoFit Laboratory |Two labs – one team]]''': fully interacting across the two labs, with [[Oroboros MitoFit lab: visiting scientists |visiting scientists]] joining us from all-over the world, gaining from and contributing to our expertise in Mitochondria and Cell Research. In our team not only the technological skills are taught and developed in mitochondrial physiology, we emphasize a top-level education in the fundamental theoretical basis of bioenergetics ([[Gnaiger 2014 MitoPathways |Gnaiger 2014]]; Abstract 2018).
-::::::::* 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. - [[Gnaiger 2014 MitoPathways |»Bioblast link«]]
-::::::::* Gnaiger E (2018) The protonmotive force under pressure: an isomorphic analysis. [[EBEC2018 Budapest HU |EBEC 2018]].
-::::* You will have access to our most recently developed and tested instrumental equipment.
-::::::* A Q-sensor is integrated into a new type of O2k. It has not yet been applied in cancer research. '''Redox regulation at the Q-junction''' fits perfectly the topic of the effects of pH and hypoxia on respiration and ROS production (Komlodi et al 2018).
-::::::::* Komlodi T, Hunger M, Moore AL, Gnaiger E (2018) Electron supply to the Q-junction: assessment of mitochondrial respiration, H<sub>2</sub>O<sub>2</sub> flux and the redox state of the Q-pool. [[EBEC2018 Budapest HU |EBEC 2018]].
-::::::* Our software development for analysis of '''oxygen kinetics of mitochondrial respiration''' supports analysis of measurements at the extremes of low oxygen towards anoxia, which are technologically unique and the method has now evolved into an easily applicable routine procedure (Meszaros et al 2018)). Using our more difficult software approach developed more than 20 years ago, we published a few papers on oxygen kinetics in cancer cells (see below). This can now be followed up with a fast way to obtain data relevant to evaluate cancer metabolism.
-::::::::* Meszaros AT, Haider M, Gnaiger E (2018) Tissue- and substrate-specific patterns in the oxygen kinetics of mitochondrial respiration. [[EBEC2018 Budapest HU |EBEC 2018]].
-::::::::* Kristiansen G, Hu J, Wichmann D, Stiehl DP, Rose M, Gerhardt J, Bohnert A, ten Haaf A, Moch H, Raleigh J, Varia MA, Subarsky P, Scandurra FM, Gnaiger E, Gleixner E, Bicker A, Gassmann M, Hankeln T, Dahl E, Gorr TA (2011) Endogenous myoglobin in breast cancer is hypoxia-inducible by alternate transcription and functions to impair mitochondrial activity: a role in tumor suppression? J Biol Chem 286:43417-28. - [[Kristiansen_2011_J Biol Chem |»Bioblast link«]]
-::::::::* Smolková K, Bellance N, Scandurra F, Génot E, Gnaiger E, Plecitá-Hlavatá L, Ježek P, Rossignol R (2010) Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia. J Bioenerg Biomembr 42:55-67. - [[Smolkova_2010_J Bioenerg Biomembr |»Bioblast link«]]
-::::* We proceed with prototype development for integrating measurements of NADH autofluorescence, cytochrome redox spectrophotometry, and ratiometric spectrofluorometry into our [[NextGen-O2k_innovation |'''NextGen-O2k''']]. Four NextGen-O2k prototypes are available in our lab but nowhere else in the world. Adding some measurements of NADH redox state to the above parameters respiration, ROS production, Q-redox state and mt-membrane potential yields a powerful analysis of mitochondrial respiratory states and rates, with good chances of high-level publication.
-::::* Collaboration with the group of Markus Keller is planned to be continued, fusing his advanced technique on '''cardiolipin''' analysis with our O2k technology.
-::::::::* Oemer G, Lackner L, Muigg K, Krumschnabel G, Watschinger K, Sailer S, Lindner H, Gnaiger E, Wortmann SB, Werner ER, Zschocke J, Keller MA (2018) The molecular structural diversity of mitochondrial cardiolipins. Proc Nat Acad Sci U S A 115:4158-63. - [[Oemer_2018_Proc Nat Acad Sci U S A |»Bioblast link«]]
-::::* We are upgrading our team from August to September with four additional postdocs, who will contribute to the vibrating research atmosphere in our lab.
-::::* TRACT supports participation in international conferences and outreach activities. We want to draw your attention to the next MitoEAGLE and MiPschool, where students are fully supported by MitoEAGLE:
-::::::::* [[MiPschool_Tromso-Bergen_2018]]
-:::: [[Gnaiger E |Erich Gnaiger]] and [[Laner V |Verena Laner]], Innsbruck, 2018-06-21
-== TRACT Marie Skłodowska-Curie Project - News and Events ==
-:::: '''TRACT''' supports eleven PhD fellows to complete research projects in the three critical areas: biomarker discovery, molecular resistance mechanisms and metabolic transformation mechanisms.
-This will allow for the discovery of novel insights into the molecular and cellular basis of oral and oesophageal cancer and generate new diagnostic tools and therapeutics that will improve patient response and survival.<br />
-::: '''Web'''
-::::* [http://www.qub.ac.uk/sites/TraininginCancerMechanismsandTherapeutics TRACT Website]
-::::* [https://twitter.com/TRACT_ITN Twitter: TRACT_ITN]
-::: '''Events'''
-{{#ask:[[Category:Publications]] [[Additional label::TRACT]]
-|?Was published in year=When
-|?Has title=Where
-|format=broadtable
-|limit=5000
-|offset=0
-|sort=Was published in year
-|order=ascending
-}}
-<br/>
-::::* '''2017-07-23 - 2017-07-30''' [[MiPschool Obergurgl 2017|10th MiPschool MitoEAGLE Obergurgl]]
-== TRACT: Call H2020-MSCA-ITN-2016 - Contents and Aims==
 :::: '''In 2012, 8.2 million people worldwide died of cancer, of which 5.3% or over half a million deaths were accounted for by oral and oesophageal cancer (OOC)'''
@@ Line 104: / Line 28: @@
-::: '''Objectives'''
+=== Objectives ===
 :::: '''TRACT provides ESRs with exposure to a collaborative network''' of European academic and industrial experts working in the complementary domains of cancer metabolism, metabolomics, high-resolution imaging, bioinformatics, biomarker identification, computational modelling, medicinal chemistry, target validation, drug development, nanotechnology and translational medicine. Although there are many researchers working on OOC in the relevant domains listed above, there is a lack of integration between domains - through a programme of integrative training and research, TRACT will bring together relevant domains to deliver better diagnostics and therapeutics for OOC with the overall aim of improving patient response and survival.
@@ Line 122: / Line 45: @@
-== TRACT Marie Skłodowska-Curie Partners, PhD Fellows and Supervisors ==
+== Coordinator ==
-::: '''Project partners'''
+::::* TRACT project manager: [[McPartlin C|Catherine McPartlin]] - [https://www.tcd.ie/ Trinity College Dublin] - IE
+::::* TRACT project coordinator: [[Zisterer D|Dr Daniela Zisterer]] - [https://www.tcd.ie/ Trinity College Dublin] - IE
+== Network ==
+=== Project partners ===
 ::::*	[https://www.tcd.ie/ Trinity College Dublin] - IE
 ::::*	[http://wiki.oroboros.at/index.php/OROBOROS_INSTRUMENTS Oroboros Instruments GmbH] – AT
 ::::*	[http://www.uv.es/ Universitat de València] - ES
 ::::*	[http://en.unisi.it/ Universitá degli studi di Siena] - IT
 ::::*	[http://www.qub.ac.uk/ The Queen’s University of Belfast] - UK
@@ Line 144: / Line 70: @@
 [[Image:The_Queen's_University_of_Belfast.png‎|200px|The Queen's University of Belfast]]
-::: '''Coordinators'''
-:::: TRACT project manager:
-::::: [[McPartlin C|Catherine McPartlin]]
-::::: [https://www.tcd.ie/ Trinity College Dublin] - IE
-:::: TRACT project coordinator:
-::::: [[Zisterer D|Dr Daniela Zisterer]]
-::::: [https://www.tcd.ie/ Trinity College Dublin] - IE
-:::: Oroboros project manager:
-::::: [[Laner V|Mag. Verena Laner]]
-::: '''Further partner organisations'''
+=== Further partner organisations ===
 ::::*	[http://www.agilent.com/home/ Agilent Technologies] - UK
@@ Line 177: / Line 92: @@
-::: '''PhD Fellows and Supervisors'''
+=== PhD Fellows and Supervisors ===
 :::: Total applications received for TRACT PhD Positions: 150
@@ Line 197: / Line 112: @@
 | 3 || Modulation of salivary inflammatory markers in patients undergoing radiotherapy for OSCC || [[Principe S|Sara Principe]] || UVEG (Valencia, Spain) || [[Bagan J|Prof. Jose Bagan]] || Biomarker Discovery (WP2)
 |-
-| 4 || A pathways-based approach to identify determinants of drug resistance in OAC || [[McCabe N|Niamh McCabe]] || QUB (Belfast, United Kingdom) || [[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Resistance Mechanisms (WP3)
+| 4 || A pathways-based approach to identify determinants of drug resistance in OAC || Niamh McCabe || QUB (Belfast, United Kingdom) || [[Turkington R|Dr. Richard Turkington]] & [[Kennedy R|Prof. Richard Kennedy]] || Resistance Mechanisms (WP3)
 |-
 | 5 || Inflammatory caspases as biomarkers for OAC? Determining the role of inflammatory caspases in OAC development and resistance || [[Flis E|Ewelina Flis]] || TCD (Dublin, Ireland) || [[Creagh E|Prof. Emma Creagh]] & [[Murray J|Dr. James Murray]] || Resistance Mechanisms (WP3)
@@ Line 209: / Line 124: @@
 | 9 || Pre-clinical evaluation of targeting autophagy for the treatment of OSCC || [[Magnano_S|Stefania Magnano]] || TCD (Dublin, Ireland) || [[Zisterer_D|Prof. Daniela Zisterer]] & [[O’Sullivan J|Dr. Jeff O’Sullivan]] || Resistance Mechanisms (WP3)
 |-
-| 10 || Metabolic profiles in normal, dysplastic and cancerous oral cells || '''Vacant position''' || Oroboros Instruments (Innsbruck, Austria) || [[Gnaiger_E|Prof. Erich Gnaiger]] || Metabolic Transformation (WP4)
+| 10 || Metabolic profiles in normal, dysplastic and cancerous oral cells || [[Garipi E|Enis Garipi]] || Oroboros Instruments (Innsbruck, Austria) || [[Gnaiger_E|Prof. Erich Gnaiger]] || Metabolic Transformation (WP4)
 |-
 | 11 || Mitochondrial function linked to metabolic differences in normal, dysplastic and cancerous oral cells || [[Karavyraki_M|Marilena Karavyraki]] || TCD (Dublin, Ireland) || [[Porter RK|Prof. Richard Porter]] || Metabolic Transformation (WP4)
 |}
+== Oroboros involvement ==
 ::: '''WP4: Metabolic transformation'''
@@ Line 221: / Line 139: @@
 ::::* '''Identify differential novel drug targets in the cancer cells'''
-:::: TRACT examines metabolic transformation mechanisms in OOC with the aim of identifying new drug targets for future therapeutic development. Metabolic transformation is a universal property of tumour formation and is a rich source of targets for development of therapeutic interventions. ESR 10 (Oroboros recruit; TCD secondment) will further characterise the bioenergetic and metabolic differences in normal, dysplastic and cancerous oral cancer cells using the Oroboros O2k-MultiSensor system. This approach will identify differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells. Factors that control mitochondrial dynamics in cancer cells have also emerged as possible therapeutic targets.
+::::: TRACT examines metabolic transformation mechanisms in OOC with the aim of identifying new drug targets for future therapeutic development. Metabolic transformation is a universal property of tumour formation and is a rich source of targets for development of therapeutic interventions. ESR 10 (Oroboros recruit; TCD secondment) will further characterise the bioenergetic and metabolic differences in normal, dysplastic and cancerous oral cancer cells using the Oroboros O2k-MultiSensor system. This approach will identify differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells. Factors that control mitochondrial dynamics in cancer cells have also emerged as possible therapeutic targets.
-:::: The dynamic structure of the mitochondria in mammalian cells is defined by the opposing forces of fission and fusion, but the regulation of these mitochondrial processes is poorly understood. This is an emerging area in cancer research where cutting-edge imaging technologies are merging with molecular and cellular biology techniques. Pilot studies performed by Porter in TCD have identified a key molecule involved in controlling mitochondrial abundance (namely SIRT3) as a determinant of drug resistance in some solid cancers. ESR 11 (TCD recruit; Oroboros secondment) will establish the relationship between mitochondrial abundance, morphology, functional proteins involved in mitochondrial dynamics and metabolic differences in normal, dysplastic and oral cancer cells. This new knowledge will lead to the identification of novel therapeutic targets.
+::::: The dynamic structure of the mitochondria in mammalian cells is defined by the opposing forces of fission and fusion, but the regulation of these mitochondrial processes is poorly understood. This is an emerging area in cancer research where cutting-edge imaging technologies are merging with molecular and cellular biology techniques. Pilot studies performed by Porter in TCD have identified a key molecule involved in controlling mitochondrial abundance (namely SIRT3) as a determinant of drug resistance in some solid cancers. ESR 11 (TCD recruit; Oroboros secondment) will establish the relationship between mitochondrial abundance, morphology, functional proteins involved in mitochondrial dynamics and metabolic differences in normal, dysplastic and oral cancer cells. This new knowledge will lead to the identification of novel therapeutic targets.
-::: '''ESR10 - Metabolic profiles in normal, dysplastic and cancerous oral cells (Oroboros Instruments / Medical University Innsbruck)'''
-::::* '''Shao-Chiang Chang''' worked on this project successfully from 2017-Oct-01 to 2018-Jun-05.
+::::* Oroboros project manager: [[Laner V|Mag. Verena Laner]]
-::::* '''[[Bufe A |Anja Bufe]]''' was selected as a PhD fellow and started her PhD project on 2017-03-01 with Oroboros Instruments at the Medical University of Innsbruck. Her appointmant ended prematurely on 2017-06-30.
-::::* Planned secondments: TCD (duration: 2x3 months, supervisor: Prof. Richard Porter) - measure metabolic flux through (a) glycolysis, (b) pentose phosphate pathway and (c) glutaminolysis using 2H/13C NMR.
-::: '''Selected publications'''
+::::* TRACT PhD student (ESR10) at Oroboros Instruments / Medical University Innsbruck: [[Garipi E | '''Enis Garipi''', MD]] - Metabolic profiles in normal, dysplastic and cancerous oral cells
+::::: Planned secondments: TCD (duration: 2x3 months, supervisor: Prof. Richard Porter) - measure metabolic flux through (a) glycolysis, (b) pentose phosphate pathway and (c) glutaminolysis using 2H/13C NMR.
+::::: '''Shao-Chiang Chang''' worked on this project successfully from 2017-Oct-01 to 2018-Jun-05.
+::::: '''[[Bufe A |Anja Bufe]]''' was selected as a PhD fellow and started her PhD project on 2017-03-01 with Oroboros Instruments at the Medical University of Innsbruck. Her appointmant ended prematurely on 2017-06-30.
+== TRACT Events ==
+{{#ask:[[Category:Publications]] [[Additional label::TRACT]]
+|?Was published in year=When
+|?Has title=Where
+|format=broadtable
+|limit=5000
+|offset=0
+|sort=Was published in year
+|order=ascending
+}}
+== TRACT dissemination ==
+::: '''Events'''
+::::* [[Bufe 2017 TRACT PhD project abstract]]
+::::* [[Garipi 2018 MiPschool Tromso E2]]
+::::* Poster at: [[Life Science PhD Meeting 2019 Innsbruck AT]]
+== References ==
 ::::* Schöpf B, Schäfer G, Weber A, Talasz H, Eder IE, Klocker H, Gnaiger E (2016) Oxidative phosphorylation and mitochondrial function differ between human prostate tissue and cultured cells. FEBS J. - [[Schoepf 2016 FEBS J |»Bioblast link«]]
 ::::* Makrecka-Kuka M, Krumschnabel G, Gnaiger E (2015) High-resolution respirometry for simultaneous measurement of oxygen and hydrogen peroxide fluxes in permeabilized cells, tissue homogenate and isolated mitochondria. Biomolecules 5:1319-38. - [[Makrecka-Kuka 2015 Biomolecules |»Bioblast link«]]
@@ Line 238: / Line 178: @@
 ::::* Kristiansen G, Hu J, Wichmann D, Stiehl DP, Rose M, Gerhardt J, Bohnert A, ten Haaf A, Moch H, Raleigh J, Varia MA, Subarsky P, Scandurra FM, Gnaiger E, Gleixner E, Bicker A, Gassmann M, Hankeln T, Dahl E, Gorr TA (2011) Endogenous myoglobin in breast cancer is hypoxia-inducible by alternate transcription and functions to impair mitochondrial activity: a role in tumor suppression? J Biol Chem 286:43417-28. - [[Kristiansen 2011 J Biol Chem |»Bioblast link«]]
 ::::* [[Gnaiger E |''More than six'']]
+== Support  ==
+:::: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 721906