Scott A. Witt and Dr. Kim L. O’Neill, Microbiology

The human body has an automatic system for eliminating unwanted cells. When it is time for a cell to be removed, it is given a signal to divide up its parts into discrete packages and send them to other cells to be recycled. The cell eventually disintegrates. This process is called apoptosis, or programmed cell death. Every cell in the body has the mechanism, but only the ones receiving the signal will die. Sometimes, certain cells lose the ability to undergo programmed cell death. The result is a group of unwanted cells that refuse to die properly-cancer.

We proposed an experiment to override the regular apoptosis signal in cancer cells. We wanted to create a super-switch for cancer cells that would send a message to die that they could not ignore. To do this, we designed a DNA code that would greatly amplify the regular apoptosis signal, but only amplify it in cancer cells. The regular signal is a protein called Bax. The amplifier is a DNA code called the Thymidine Kinase 1 promoter (TK1 promoter).

The hypothesis is that the signal for programmed cell death can be artificially amplified only in cells that actively process the TK1 promoter. Dr. O’Neill’s previous work has demonstrated that the TK1 protein is expressed in high amounts in many types of cancer. The TK1 promoter is the adapter that determines how much protein is expressed. By attaching the adapter (TK1 promoter) to the cell death signal (Bax) we create a super-switch that is only active in cancer cells. Regular cells are not affected because the adapter does not fit properly to the healthy cell’s environment. This system is designed to overcome one of the current problems of cancer treatment & low selectivity.

The bulk of the effort so far has been directed to the creation of this DNA super-switch. By the addition of persistent effort from Brian H Ladle (also of Dr. O’Neill’s lab), we were able to construct the super-switch vector entitled TkpBax. The next step is to expose cancer cell types to this vector. Attempts have been made in this direction, but preliminary data has not been very encouraging, due to an unforeseen condition in the cell type we chose to first study. Several new more promising cell types have been identified, and we are intent on moving forward with the study.

While I personally will not be able to continue in this study, plans have been made for other students to carry on and see it to completion. I cannot overemphasize how beneficial this opportunity has been for the advancement of my education and future professional career.