A love-hate relationship: cholesterol in health and disease

Lectures: 1 session / week, 2 hours / session

7.03 Genetics
7.05 General Biochemistry
7.06 Cell Biology
Or
7.28 Molecular Biology

After World War II, a new mysterious epidemic was killing men over 55 like never before. To find out what was happening, researchers focused on a small town in Massachusetts and started the largest and longest epidemiological study of its kind. Our lives have not been the same since. The results from the Framingham Heart Study linked a person's blood cholesterol levels to the risk of having heart disease, the number one killer in western industrialized societies today. How could a small molecule like cholesterol, a major constituent of our cell membranes, be to blame? In this class, we will examine cholesterol's role in the cell and in the body as a whole, from its function as a structural component of the membrane to its function in signaling. We will learn that every cell is faced with a choice to either make cholesterol or take it up from circulating blood. How does a cell know how much cholesterol is inside it? We will talk about the transcriptional and posttranscriptional mechanisms of cholesterol sensing and of feedback regulation in cells. We will discuss cholesterol in the brain and in the circulation, 'good cholesterol' and the 'bad cholesterol' and how they are taken up and used in cells. We will consider what happens when cholesterol regulation goes awry in cholesterol-related human disorders and in animal models of such disorders. We will find out how the drugs that deal with some of these disorders were discovered, their targets and current strategies for discovering better drugs in the future.

The goal of this course is to familiarize students with reading and critically evaluating primary literature. We will discuss two papers each week. It is imperative that students read the material before class so we can analyze the papers in detail figure by figure and table by table. To prepare for class, students are expected to submit one or two discussion questions about each of the articles to be discussed that week by noon on the day of class.

This is a discussion course, so attendance is essential. If you miss a class because you were sick, you will need to do a makeup assignment. This is a pass/fail course. Your grade will be determined by your attendance, class participation and your successful completion of class assignments.

Each week you will be required to read two articles and submit one or two questions about the readings before class. There will also be two written assignments.

Assignment 1 due

Field trip to Beth-Israel Deaconess Medical Center

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