LIPOPROT

New chemical tools for profiling protein lipidation in cancer

Coordinatore	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE    more  Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD city: LONDON postcode: SW7 2AZ contact info Titolo: Ms. Nome: Brooke Cognome: Alasya Email: send email Telefono: +44 207 594 1181 Fax: +44 207 594 1418
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	209˙092 €
EC contributo	209˙092 €
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-2010-IEF
Funding Scheme	MC-IEF
Anno di inizio	2011
Periodo (anno-mese-giorno)	2011-07-17   -   2013-07-16

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE  Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD city: LONDON postcode: SW7 2AZ contact info Titolo: Ms. Nome: Brooke Cognome: Alasya Email: send email Telefono: +44 207 594 1181 Fax: +44 207 594 1418	UK (LONDON)	coordinator	209˙092.80

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'This project aims to develop chemical probes and technologies that will enable for the first time high-throughput analysis and exploration of the complex biological networks involved in protein lipidation. These chemical tools will be applied to mapping the changes in lipidation that occur in the proliferation and survival of cancer cells, with the ultimate objective of identifying and validating cellular mechanisms that can be targeted for future chemotherapy. The proposed work is multidisciplinary, combining organic synthesis with proteomics and cell biology. As such it lies at the cutting edge of chemical biology, and will permit the applicant to gain skills and independence to found an independent group in chemical biology.'

Introduzione (Teaser)

The developed world needs, and is searching, for more effective medications to fight cancer. An in-depth investigation of protein modifications has the potential to advance novel approaches in drug discovery.

Descrizione progetto (Article)

The formation of lipidated proteins is controlled by enzymes, protein-lipid transferases, and the abnormal activity of these enzymes in cancer cells has been previously reported. Novel medications that inhibit activities of these enzymes might down-regulate the cancer-promoting transformations in the cells. The EU-funded Marie Curie 'New chemical tools for profiling protein lipidation in cancer' (LIPOPROT) project aimed to develop new methods to study the levels of protein lipidation in cancer.

The main objectives were to synthesise probes for protein lipidation and validate them for high-throughput profiling for comparative analysis in representative cancer cells. Researchers successfully optimised synthesis of chemical probes to be cost- and time-efficient. Next, they characterised in-depth physicochemical properties of all novel compounds.

The scientists applied novel lipid probes to model cervical cancer cells in culture. This led to the discovery of both the identity of lipidated proteins and their exact location as well as the nature of chemical bonding that links the fats and proteins. Relative protein lipidation efficiencies and global enzymatic activities of lipid transferases were also studied in other cell models including breast cancer and colon cancer cell lines.

Researchers further utilised these models to examine the incorporation of myristic acid for protein modification in cancer, catalysed by the enzyme N-myristoyl transferase. The experiments included phenotypic and molecular analysis of the effects of N-myristoyl transferase inhibition in cancer cells. Metabolic activity measurements and quantitative proteomic analyses provided preliminary support for the hypothesis that N-myristoyl transferase is a valid drug target in cancer.

Importantly, the technologies developed by LIPOPROT are universal, and might be applied to the protein lipidation analysis in other human and animal diseases.