Three research groups from the Inst. for Cancer Res. involved in projects receiving FUGE grants
The Systems Biology of Breast Cancer
Project leader: Anne-Lise Børresen-Dale, group home page: Børresen-Dale group
Granted sum: 9 mill NOK
Main objective:
We seek to reach a more fundamental understanding of the biological dynamics of breast cancer, the aim being to be able to better identify risk factors, guide novel cancer diagnosis, predict therapeutic effects and prognosis and identify new targets for therapy. The most significant challenges in this post-genomic era of cancer research are translational in nature. We need to integrate data from multiple levels of molecular screening to identify critical, rate-limiting molecular targets for intervention. We also need to explore functions of thousands of candidate cancer genes and proteins in order to ascertain their value as risk factors, as predictive factors for therapy response and as therapeutic targets. Advanced statistical and bioinformatic tools are required for analysis, interpretation and validation. Existing statistical and computational methods and tools will be adapted and new ones will be developed to extract information from complex multidimensional and multiscale data.
Specific goals:
Granted sum: 9 mill NOK
Børresen-Dale
We seek to reach a more fundamental understanding of the biological dynamics of breast cancer, the aim being to be able to better identify risk factors, guide novel cancer diagnosis, predict therapeutic effects and prognosis and identify new targets for therapy. The most significant challenges in this post-genomic era of cancer research are translational in nature. We need to integrate data from multiple levels of molecular screening to identify critical, rate-limiting molecular targets for intervention. We also need to explore functions of thousands of candidate cancer genes and proteins in order to ascertain their value as risk factors, as predictive factors for therapy response and as therapeutic targets. Advanced statistical and bioinformatic tools are required for analysis, interpretation and validation. Existing statistical and computational methods and tools will be adapted and new ones will be developed to extract information from complex multidimensional and multiscale data.
Specific goals:
- To join forces and expertise to create a world-leading Breast Cancer Research Center including The Dept of Medical Statistic Faculty of Medicine, Dept of Informatics, Faculty of Mathematics and Natural Sciences, UiO, The Norwegian Radium Hospital, Ullevål Univ. Hospital and potentially other hospitals in the Oslo area.
- To follow the linear time course of predisposition, initiation, early stages and advanced disease and to dissect the molecular mechanisms triggered at each stage (See Table of materials, attached under Other Items, for acquired sample series from each of these time points).
- To follow the multidimentional interactions at various levels in a systems biology approach (See Table of materials for ongoing and planned studies of blood and tumor at the DNA, RNA and protein level)
Participants in The Systems Biology of Breast Cancer
Participants (active partners (in bold) and active collaborators (in italic)) and organization of The Systems Biology of Breast Cancer project.
NucPro: Epigenetics of nuclear programs - from genome-wide landscapes to individual factor mechanisms
Ola Myklebost
Granted sum: 11 mill. NOK
Participating research group from the Institute for Cancer Research: Ola Myklebost's group
This application is a joint effort from four independent research groups to exploit the microarray technology in order to solve problems in the field of the plasticity of gene expression and transcription control. The aim is to take advantage of the national microarray facility and use microarray approaches to address basic issues in the regulation of gene expression. A strategy is planned to ensure that all members of the consortium will benefit from the common resource of technical skills. The four groups behind this application have demonstrated competence in complementary fields of transcription regulation:
- Myb-related factors (Gabrielsen group)
- oncology and microarray technology (Myklebost group),
- nuclear receptors (Saatcioglu group)
- manipulation of gene expression - nuclear reprogramming (Collas group)
Read more (from the home page of Ola Myklebost's group)
Protein aggregation and degradation in aging and disease
H. Stenmark
Granted sum to project: 8,6 mill NOK
Participating research group from the Institute for Cancer Research: Harald Stenmark's group
Summary of the project:
Hundreds of proteins encoded by the human genome have the propensity to form cytoplasmic aggregates under certain conditions. Although the mechanisms of intracellular protein aggregation are poorly understood, it is well known that deposits of aggregateted proteins are highly associated with aging, cancer and neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease. Clarifying how intracellular protein aggregates form, and how they are degraded, is thus predicted to yield novel therapeutic targets in these diseases. In this joint project, involving research groups at the University of Tromsø and the Norwegian Radium Hospital, we aim to investigate how normal cells recognize and dispose of cytoplasmic protein aggregates, and how protein aggregates affect cellular functions. Polyubiquitination of protein aggregates is thought to facilitate their degradation, although proteasomes appear to of minor importance for their catabolism. In contrast, autophagy, a process that involves lysosomal degradation of cytoplasm, appears to play an important role in the degradation of protein aggregates. We will pursue recent clues our laboratories have obtained concerning the cellular machineries that recognize and degrade polyubiquitinated protein aggregates. These analyses will involve proteomics, structural biology, molecular imaging and animal models.
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