Cellular Decision Making in Cancer

Research

If a cell is damaged, does it repair itself or decide to self-destruct? And just how does the cell make that decision? CDMC will develop a multi-scale narrative of how single-molecule events integrate protein networks to determine cell fate.

The CDMC theme has unique tools at its disposal to help unravel both the complexities of individual cells and of larger systems using new experimental and computational approaches. These experiments hold promise for personalized medicine and other healthcare advances.

Because cancer in particular is the result of cell decision-making run amok, the theme members will focus on that disease. However, because cellular decision-making is involved in an array of other activities, the theme will also investigate such activities as cell maintenance, replication, repair, recombination, programmed cell death —apoptosis — as well as the decision by a stem cell to differentiate into a specific type of tissue or a cell’s response to a viral infection, when it will crank up the production of antiviral proteins.

The theme capitalizes on advances over the last few years in single molecule measurements, chemical biology and computational genomic, which has resulted in techniques unique to IGB and the University. Those tools include FISH, a fluorescent labeling technique in situ  (i.e. in vivo) that can image individual mRNA molecule in a single cell, and SiMPull, for “single molecule pull down,” a way to isolate and analyze single protein complexes directly from cell extracts. Currently SiMPull works in 2 minutes with a group of 10 cells and shortly it will succeed at the single cell level. Western Blots, the current technique for analysing proteins, takes 5,000 cells, large quantities of reagents and antibodies and many hours to get results. The theme is also working to apply single cell FISH and SiMPull to native tissues while keeping track of spatial information of single cells within the tissues.