Field of research: Cancer Biology
Lab: David Foster
School: Manhattan Hunter Science High School
Year: 10th/ 11th Grade
Over the summer, I was doing my internship in Dr. Foster’s Lab. While working in the lab, I was assigned a project which was Targeting Survival Signals in Cancer Cells.
Phospholipase D (PLD) activity is major factor for the survival signals in cancer cells. PLD is an enzyme that catalyzes the hydrolysis of Phosphatidylcholine to generate phosphatidic acid (PA) and choline. PA, the product of PLD has many targets. However, the most important target is mTOR, which is responsible for the survival signal. mTOR stands for Mammalian Target of Rapamycin. It regulates cell proliferation and cell growth, initiation of protein synthesis and is inhibited by rapamycin. Most importantly, PA interacts with mTOR at the same site that binds rapamycin. When rapamycin interacts with mTOR, it forms an inactive mTOR. However, if PA interacts with mTOR then it forms two active complexes leading to the survival signals. From these studies, it was concluded that rapamycin competes with PA to interact with mTOR. Therefore, reduced PA production is needed for rapamycin to work effectively to inhibit mTOR.
A way to decrease PA levels – and make rapamycin more effective) is to add a primary alcohol such as ethanol or butanol. When ethanol is added, it makes a nucleophilic attack on the phosphate of phosphatidylcholine and generates Phosphatidyl-ethanol instead of PA. As a result, rapamycin binds mTOR more easily and blocks the protein synthesis needed for the survival signals. Studies have also shown that moderate alcohol consumers have reduced incidence of certain cancers – such as lymphoma. During this past summer, I performed experiments, in which I treated different cancer cell lines with ethanol and observed its effects on the survival of these cells. When ethanol concentration was increased, the number of dead cells increased while the number of living cells increased. As expected, ethanol suppressed the survival signals of these cancer cells leading to cell death.
Working in Dr. Foster's lab was a remarkable experience as I learned many new important things by working with the professor and the lab members.