This is an actual question from the exam I mentioned last week:

You have just started your own lab at Red Sox Nation University and you decide you want to start a new research direction for your group. You have isolated a new organism called Yankees loserii that, upon infection, causes an abnormal swelling of the head. Your first mission is to gain a better understanding of how Y. loserii colonizes the host and causes disease. You have a few pieces of preliminary data you've gleaned from the literature that provide a starting place. An in vitro system has been set up in which Y. loserii has been shown to colonize a particular host cell line called AROD-S. In this model system, Y. loserii is cytotoxic and thus kills the AROD-S cell line after 48 hrs of exposure. Standard genetic tools such as transposons, gene fusions, plasmids and antibiotic-resistance markers are also available to you. However, no one has yet felt it is worth the money to sequence this organism. Of course, your lab is well stocked with all the typical equipment including incubators, microscopes, etc.

A. Design a genetic screen to identify factors required for Y. loserii to kill the AROD-S cell line.

B. Design a second screen in which mutants identified in the screen above can be sorted into the two following classes: a. Genes required for the colonization of the AROD-S cell line, or b. Genes required for killing of the AROD-S cell line

C. How would you use an enrichment to facilitate the screen you designed in Part A?

D. As a result of the screen performed above, you identify a key toxin called WS-04 that is required for killing the AROD-S cell line. In the course of your experimentation, you discover that this toxin is only expressed when Y. loserii is exposed to the AROD-S cell line, but NOT when Y. loserii is grown on laboratory medium. Based on your preliminary data, Dr. Taylor hyothesizes that expression of the gene encoding WS-04 is repressed on laboratory medium. Using the genetic tools at your disposal, describe how you would design and implement a genetic slection to identify the repressor of the gene encoding WS-04.

I got a kick out of it (well except for part C, which kicked my ass).