Synthetic Lethal Interactions with nucleophosMin 1

Información del proyecto

SLIM

Identificador del acuerdo de subvención: 703668

DOI

10.3030/703668

Proyecto finalizado el 16 Marzo 2018

Fecha de la firma de la CE 15 Marzo 2016

Fecha de inicio 1 Julio 2016

Fecha de finalización 30 Junio 2018

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 178 156,80

Aportación de la UE

€ 178 156,80

Coordinado por

CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH
Austria

Objetivo

Less than 25% of patients diagnosed with acute myeloid leukemia (AML) survive longer than 5 years. Current treatment regimen are based on non-specifically acting cytotoxic drugs that cause severe side effects. More effective and more specific, targeted therapies are thus needed. Progress, however, has long been hampered by a lack of understanding of the molecular vulnerabilities of the disease.

We here propose to identify and study synthetic lethal interactions with mutations in nucleophosmin 1 (NPM1) in AML. Up to 35% of AML patients bear mutations in NPM1 leading to a localization of this nucleolar protein to the cytoplasm and a characteristic change in gene expression pattern. Moreover, NPM1 mutations appear to be driver events and stable over multiple courses of therapy and relapse. Identifying cellular pathways or proteins that are essential in an NPM1 mutated background but not in NPM1 wild type cells may thus not only contribute to a better understanding of NPM1 biology but also yield entry points for the development of drugs that selectively kill NPM1 mutated AML cells.

We will take an integrated chemical biology approach to first identify small molecules that selectively kill NPM1 mutated over NPM1 wild type cells and then elucidate their mode of action to gain insight into the underlying biology. This project thus uniquely builds on the longstanding experience of the host laboratory and institute in chemical screening, the elucidation of the mode of action of small molecules and in hematological malignancies.

The proposal is designed to complement the experienced researchers current knowledge in chemical synthesis, assay development, solid tumor biology and small animal imaging techniques to become a well-rounded chemical biologist with a disease focus on solid and liquid cancers. The hosting institution will gain from the researcher´s chemical expertise and find opportunities to expand its network of international collaborations.

Ámbito científico (EuroSciVoc)

• ciencias médicas y de la salud › biotecnología médica › ingeniería genética › terapia génica
• ciencias médicas y de la salud › ciencias de la salud › enfermedades inflamatorias
• ciencias médicas y de la salud › medicina clínica › gastroenterología › enfermedad inflamatoria intestinal
• ciencias médicas y de la salud › medicina básica › neurología › esclerosis múltiple
• ciencias médicas y de la salud › medicina clínica › oncología › leucemia

Palabras clave

• acute myeloid leukemia
• nucleophosmin 1
• synthetic lethal interactions
• chemical proteomics
• high throughput screening

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2015-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF)
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2015

Coordinador

CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH

• Aportación neta de la UEn: € 178 156,80
• Dirección: LAZARETTGASSE 14 AKH BT 25.3 ; 1090 Wien ; Austria
• Región: Ostösterreich › Wien › Wien
• Tipo de actividad: Private for-profit entities (excluding Higher or Secondary Education Establishments)
• Coste total: € 178 156,80