Syllabus

Course Meeting Times

Lecture: 1 session / week, 2 hours / session

Prerequisites

Recommended prerequisites are:

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

7.28 Molecular Biology

Course Description

How do scientists discover the basic biology underlying human diseases? Simple organisms such as baker's yeast, nematodes, fruit flies, zebrafish, mice and rats have allowed biologists to investigate disease at multiple levels, from molecules to behavior. In this course students will learn strategies of disease modeling by critically reading and discussing primary research articles. We will explore current models of neurodegenerative diseases such as Parkinson's disease, childhood genetic diseases such as Fragile X syndrome, as well as models of deafness and wound healing. Using these examples, we will discuss the pathology of each disease and consider the benefits and drawbacks of a variety of experimental approaches.

Some researchers use "environmental" models in which pharmacological agents are used to perturb in an experimental organism the molecules or cells that correspond to those affected in human patients. Alternatively, if a specific gene is known to be linked to a disease, many powerful tools exist to create "genetic" models: researchers can remove, mutate, overexpress or misexpress the gene in an experimental organism to attempt to recreate what happens in the cells of a human patient. Finally, researchers can design genetic screens to identify new genes that might be involved in a particular disease process. We will discuss these approaches as well as the advantages offered by each simple organism. We will visit an MIT research lab that currently studies Huntington's disease using the fruit fly Drosophila melanogaster. Our goal will be to understand the strategies biologists use to build appropriate models of human disease and to appreciate both the power and limitations of using simple organisms to analyze human disease.

Goals

The objectives of this course are to introduce students to the primary scientific literature as well as to expose students to strategies and techniques used to study human diseases using simple organisms. By the end of the class students should be able to:

1. Read, understand and critically analyze primary research articles
2. Name commonly studied simple organisms and understand the experimental advantages and disadvantages of each
3. Describe techniques used to produce loss-of-function or gain-of-function of a gene
4. Describe genetic and non-genetic approaches to disease modeling
5. Appreciate the difference between human diseases caused by loss-of-function or gain-of-function of a gene and understand the advantages and disadvantages of building genetic models of each
6. Design experiments using the strategies, techniques and considerations discussed in the course

Format

This course will meet weekly for two hours. Students will be required to read two papers each week and be prepared to discuss them in class. We will focus on the principles of experimental design, use of controls, and interpretation of the experimental data. We will also discuss the advantages and disadvantages of the experimental approaches with respect to the disease being modeled. The final 15 minutes of each class will consist of an introductory talk about the next week's topic. In week 6, we will visit the laboratory of Professor Troy Littleton in the MIT Picower Institute of Learning and Memory. We will tour the lab and attend a short seminar about the lab's work on Huntington's disease using Drosophila.

Calendar