Genetics 553


Spring 2002

Module 1

 

Dr. Carol Sibley

Tuesday- Thursday
12 to 1:20
K350

Introduction:

The overall theme of this five week section of the course is this: How can advances in basic science contribute to the solution of practical problems? This focus is inherently interdisciplinary; we will explore a wide range of approaches and techniques that have been integrated to study drug resistance, pathology and evolution in Mycobacterium tuberculosis, the bacterium that causes TB in humans. Infection with this pathogen is rising explosively worldwide, particularly in the former Soviet Union, Southern Africa and East Asia. More than 3 million people a year die from TB, more than from any other single pathogen. Since individuals infected with HIV are particularly vulnerable to TB, the rate of increase in TB has accelerated worldwide, and only recently slowed in the developed countries of Western Europe and the US.

Drugs offer the only current treatment for TB; no effective vaccines have been developed (although this is a controversial and interesting point). The selection pressure exerted by the drugs is intense, and the genetically expected outcome has rapidly been realized: mutation in the genes that encode the drug targets and the selection of drug resistant populations.

I will provide some background on the biology of M. tuberculosis and a very small amount of background on the disease it causes in humans. We will then brainstorm to define key questions that are currently paramount, and read and discuss papers that describe the necessary tools for answering these questions. This way of approaching the course has another objective. In your scientific career, you will almost certainly change your primary area of research several times. At each juncture, you will need to rapidly survey an unfamiliar field, find and understand the foundations of  current work, identify the key questions of relevance to that field, and develop and apply the tools that are available to answer those questions. I presume that infectious disease research in general, and M. tuberculosis in particular are unfamiliar to you. I hope that the approach outlined below will give you practice in this important skill.

In choosing initial papers for our study, I have focused on work that has a solid foundation in basic science, but has made a contribution that suggests practical avenues for public health. I will try to set the stage in the first two classes. I will expect you to read any assigned papers before the day listed for a discussion. The papers will be accessible through the web site, and I will also put hard copies in J205. I will ask individuals to summarize, critique, etc., so that we can see how that set of papers fits into the larger scheme. After the two initial introductory classes, individuals or small groups will be gathering critical information, and reporting back to the class. There will be a paper due in class on Tuesday, May 2, but I have not yet decided on the focus for that assignment.

Other useful sites:

http://molepi.stanford.edu/tblinks.html

http://www.who.int/gtb/