KP TRANSPORT

Identifying and characterising transmembrane transporters of tryptophan and kynurenine in normal and cancerous brain tissue

Coordinatore	DEUTSCHES KREBSFORSCHUNGSZENTRUM    more  Organization address address: Im Neuenheimer Feld 280 city: HEIDELBERG postcode: 69120 contact info Titolo: Dr. Nome: Ina Cognome: Wiest Email: send email Telefono: +49 6221 422700 Fax: +49 6221 422708
Nazionalità Coordinatore	Germany [DE]
Totale costo	161˙968 €
EC contributo	161˙968 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2013-IEF
Funding Scheme	MC-IEF
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-09-01   -   2016-08-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	DEUTSCHES KREBSFORSCHUNGSZENTRUM  Organization address address: Im Neuenheimer Feld 280 city: HEIDELBERG postcode: 69120 contact info Titolo: Dr. Nome: Ina Cognome: Wiest Email: send email Telefono: +49 6221 422700 Fax: +49 6221 422708	DE (HEIDELBERG)	coordinator	161˙968.80

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 Obiettivo del progetto (Objective)

'The catabolism of the essential amino acid tryptophan (Trp) by tumour cells expressing either IDO1/2 or TDO has been associated with malignant tumour progression and poor patient survival. Expression of these rate-limiting genes leads to both depletion of Trp and accumulation of the Trp breakdown product kynurenine (Kyn) in the tumour microenvironment. Kyn has recently been shown to act as a ligand for the aryl hydrocarbon receptor (AHR), causing its nuclear translocation and resulting in expression changes which in tumour cells result in increased survival and motility, whilst in T-cells induce anergy and apoptosis.

Although the membrane transport protein LAT1 is known to act as a Trp/Kyn exchanger, accumulating evidence from transport kinetics studies clearly indicate the presence of highly specific, as yet unidentified Trp and Kyn transporters. Identifying the transport proteins responsible would offer a significant therapeutic target not only for aggressive, hard to treat brain cancers such as gliomas, but also in a number of neurodegenerative and auto-immune disorders in which the catabolism of Trp has been shown to be altered.

I propose to do precisely this by expanding on discoveries I made during my studies of the role of the Trp catabolite 3-hydroxykynurenine in Huntington’s Disease, wherein I took advantage of unique features of Drosophila physiology to identify a number of candidate Trp/Kyn transporter proteins. To fully realise the potential of my discoveries I should like to characterise the human homologs of these transporters in glioma culture and in vivo models, which will require me to change both my scientific field and model system.

To gain the required expertise I am applying for an IEF to train with Michael Platten's group at the DKFZ in Germany, a world leading cancer research center which has developed a number of unique reporters for Trp and Kyn levels that are essential to my characterisation of the transporters identified.'