Course Meeting Times
Lectures: 1 session / week, 2 hours / session
At least one of the following courses:
7.05 General Biochemistry
7.06 Cell Biology
7.08 Biological Chemistry II
Cancer is a leading cause of death worldwide. Cancer involves uncontrolled cell growth, resistance to cell death, failure to differentiate into a particular cell type and increased cellular motility. A family of gate-keeper genes, known as tumor suppressor genes, plays important roles in preventing the initiation and progression of cancer. Among these, p53 is the most famous. More than 50% of human cancers harbor mutations in or deletion of p53. p53 is induced by upstream signals, such as DNA damage and hyperactive cell-growth signals. The p53 protein, functioning as a transcription factor, binds to the promoters of many target genes involved in the cell cycle, programmed cell death (apoptosis) and DNA repair. Because of its essential role in maintaining genomic integrity, p53 is often called the guardian of the genome.
During this course, we will study how p53 serves as a pivotal tumor suppressor gene in preventing cancer. We will examine the discovery of the p53 protein, the spectrum of p53 mutations in human cancer and the role of p53 as a transcription factor. In addition, we will discuss the function of p53 in DNA damage, cell death, cell cycle regulation, and genome integrity. We will also consider some recent studies of p53 mutant mouse models and the regulation by p53 of small RNA expression. Finally, we will discuss how future cancer treatments might be achieved by therapies that restore p53 function to tumor cells.
The objectives of this course are:
- List and define the hallmark characteristics of cancer.
- Name and discuss important cancer pathways regulated by p53.
- Read, comprehend, critically analyze and integrate knowledge from primary research articles.
- Explain molecular and cellular techniques commonly used in cancer biology and formulate how to apply them to answer new questions.
- Design experiments to test whether a gene is important in cancer.
The content of this course will be based on the primary research literature. For each class, students will be assigned to read two papers and formulate two questions per paper prior to each class. Questions might pertain to background, interpretation of results, a technique, follow-up experiments, etc. During class we will discuss the papers interactively as a group. Students might be asked to discuss specific figures or tables to answer questions about the papers. At the end of each session, the instructor will introduce the papers for the next week.
This course is graded pass/fail. Grading will depend on student attendance, participation in class discussions and completion of two assignments.
||Introduction to the course
||p53 first described
||An oncogene turned out to be a tumor suppressor
||p53 mutation in cancer
||p53 and cancer mouse models
||p53 and programmed cell death (apoptosis)
||Hand out papers for written presentation
||p53 and cell cycle regulation
||p53, DNA damage and genome integrity
||Written assignment due
||p53 and Mdm2
||p53 and microRNA
||Hand out papers for oral presentation
||p53 restoration therapy