Multiple perturbation analysis of cancer pathways癌症的途径多摄动分析.pptVIP

How about a Master’s project in the area of cancer systems biology? We offer projects in the following areas: Reverse engineering of cancer pathways Control of the cancer cell phenotype using drug combinations Predicting phenotype responses to cellular perturbation from array data Contact for more info: nelander@cbio.mskcc.org (please attach a CV) Previous project workers: Frank Eriksson, Mat Stat, Chalmers Darima Lamazhapova, Cambridge University Erik Larsson, Wallenberg lab, GU Tanya Lobovkina, Chemistry, Chalmers Multiple Perturbation Analysis of Cancer Pathways Sven Nelander Computational Biology Center / Chris Sander group Memorial Sloan-Kettering Cancer Center New York Outline Perturbing cancer cells - key questions Building models for combinatorial perturbation of breast cancer pathways Whole-genome RNAi screening to extend the TGF-beta pathway Work in cancer genomics and related areas Cancer A broad class of diseases exhibiting uncontrolled growth, tissue invasion and metastasis. Gradual progression towards a more malignant phenotype Acquisition of mutations that affect a specific set of processes Growth factor signaling Apoptosis DNA repair Cell cycle regulation Differentiation Selective targeting of cancer pathways by small compounds Tumors contain multiple genetic abnormalities Copy number alterations (MSKCC study). Sequence alterations. 90 mutated genes per tumor in breast and colon cancer (Sj?blom et al, Science 2006) Promoter hypermethylation. A role for systems biology? Key types of question: How will a melanoma cell line with mutation X respond to drug Y? Will drug X synergize with drug Y? Which regulatory interactions are implicated by the observed responses? What’s the mechanism of action of drug X? Pathway maps are ambiguous, incomplete and have unclear predictive value. Expert intuition is likely to fail in complicated cases. To facilitate prediction and inference, mathematical models can be employed. Des