As a graduate student, I have worked on the regulation of drug-metabolizing enzymes with Urs A. Meyer. All of us are exposed in our daily lives to an enormous number of foreign compounds, and a prime subject of study are drugs used clinically or under development, since we need to understand very well how they are metabolized and cleared from the body, in order to avoid too strong or too weak effects, and to prevent adverse side effects.

In our livers, there is an elaborate system of enzymes that is able to recognize these foreign compounds, and chemically alter them in a way that the body can excrete them more easily. This is a formidable challenge, since this system needs to be able to process chemical compounds it may never have seen before. In some way, thus, this task is akin to that of the immune system that protects us from insult from intruding bacteria or viruses.

Central in this system is a family of enzymes known as cytochromes P450, which oxidize foreign compounds, and make them more water-soluble in this way. Most interestingly, our body has a mechanism to react to the presence of too many foreign compounds, it begins to increase the production of cytochrome P450 enzymes and of other, related enzymes as to more speedily get rid of this foreign assault. During my Ph.D. work, I have characterized this defense mechanism, which is called drug induction. I could show that the transcription factors that effect the up-regulation of cytochromes P450 and of the first step of heme biosynthesis, necessary for functional detoxification, are the same, and that this indicates a well-coordinated response of the body to foreign molecules.

In this project, my interest in bioinformatics became more concrete, and led me to the development of NUBIScan, an algorithm to detect nuclear receptor binding sites in DNA.

No Comments »