1. You are studying a particular type of lung cancer, small-celllung carcinoma. You are interested on driver mutations of thiscancer, that is mutations that provide strong selection advantageand thus have strong potential in initiating tumorigenesis. Youhave access to primary tumor biopsies from patients, and healthysurrounding tissue: how you can best use these tissue samples toidentify mutations underlying this particular type of lungcancer?
2. The mutation you isolated has not been characterized before;how can the crystal structure of the protein bound on DNA help youunderstand how the mutation affects the function of the protein?What are some common mutations of the p53 protein that drivecancers?
3. You believe DNA binding is affected by the identifiedmutation, and your next goal is to characterize the functionalperturbations of the mutant p53. a. Describe an in vitro approachto study the function of the mutant protein. b. Describe anexperimental approach using cultured cells that can illuminate thealtered function of the mutant protein
4. You find in #3 that the expression levels of certain miRNAsare changed as a result of the p53 mutation. a. What experimentalapproach can reveal how altered miRNA levels change Ago/miRNAtargeting of mRNAs at the transcriptome wide level? b. Whatexperimental approach can quantify altered translation levels forthe mRNAs identified in a)?
