High-content Genetic Screens

Background
Researchers are interested in examining the molecular processes that operate in normal and cancerous breast cells. One approach to this problem involves repressing every single human gene, individually and in pairs, using RNA interference (RNAi) technology. The effects of gene inactivation on specific processes, such as cell division or the response to chemotherapy drugs, can be assessed using automated imaging methods.

This technique allows us to rapidly identify genes and proteins that are involved in specific aspects of cell behaviour. Every gene that we identify in these screens has the potential to become a target for new chemotherapy drugs.

Aims and Relevance
Several screens are currently in progress to identify:

  • genes that interact with known breast cancer-related genes.
  • gene variants that make breast cancer cells more or less sensitive to therapeutic drugs in different tumour types.
  • genes that are involved in the proliferation of various types of stem cells, and in their differentiation into other cell types

Recent related papers from the Department of Breast and Molecular Oncology

  • Potratz JC, Saunders DN, Wai DH, Ng TL, McKinney SE, Carboni JM, Gottardis MM, Triche TJ, Jürgens H, Pollak MN, Aparicio SA, Sorensen PH. Synthetic lethality screens reveal RPS6 and MST1R as modifiers of insulin-like growth factor-1 receptor inhibitor activity in childhood sarcomas. Cancer Res. 2010 70(21):8770-81.
  • Poon SS, Wong JT, Saunders DN, Ma QC, McKinney S, Fee J, Aparicio SA. Intensity calibration and automated cell cycle gating for high-throughput image-based siRNA screens of mammalian cells. Cytometry A 2008: 73(10):904-17