You are the resident biochemical scientist at a pharmaceutical company and you are part of a research group working on drug development targeting pancreatic cancer. You come across the attached review (Murthy et al. 2018) on the role of PI3K signaling in PDAC, the most aggressive form of pancreatic cancer. Your company has access to a pancreatic cancer cell line and a healthy pancreatic cell line that you can grow and manipulate. Your company also has access to a 2 million compound library to screen for small molecule drugs against any protein of interest. Your job is to read the above-mentioned review carefully and propose two sets of experiments (as explained in 2A.-2C. below) based on the assays available at your company. Available protein-based assays: a. Ability to delete a protein of choice from these cell lines. b. Ability to overexpress or introduce a protein of choice into these cell lines. c. Ability to measure cell growth and death. d. Ability to measure ligand-protein binding on-rate (kon) and off-rate (koff) constants. e. Ability to measure protein function for any protein of interest (a tall order in practice!). Target identification experimental design: 2A. Use the review to hypothesize about two of the proteins that can serve as promising therapeutic targets for PDAC. Then design experiments that will test your hypothesis. Drug discovery experimental design: 2B. We will now assume that you have identified those two proteins as potential targets to inhibit for PDAC. Now create an experimental design using the above-mentioned protein-based assays to find small molecule drugs that will serve as inhibitors for those proteins. 2C. Will these drugs work in cancer patients who have mutations in those proteins? If not, what is a potential work-around? What are the potential benefits or drawbacks of using these two drug candidates together in a drug combination?