GMS PA801S (Spring): Protein Modification and Molecular Basis of Human diseases

This course examines more than a dozen major posttranslational modifications that contribute to the protein diversity of structure and function and examines how uncontrolled posttranslational modifications contribute to human diseases.

Most proteins undergo some form of modification after translation (after the messenger RNA code has been translated into the amino acid sequence code of nascent proteins). Post-translational modifications such as glycosylation, phosphorylation, methylation and ubiquitination, to name a few, serve many functions. Post-translational modifications are particularly important for the studying of human diseases where protein modification on multiple gene products is considered key culprits, such as heart diseases, cancer and diabetes.

It could be argued that posttranslational modifications is evolved to increase the diversity of functional groups on proteins beyond those in the side chains of the 20–22 amino acids incorporated into nascent proteins. Posttranslational modification enables proteins with new function, new recognition for partner proteins, turns on and off enzymatic activity, and controls the lifetime and location of such proteins in living cells. Indeed, posttranslational modifications of proteins are evolved to expand nature’s repertoire by increasing the inventory of side chains available to proteins. Usually for each type of protein modification, there is an associated class of enzymes dedicated to those protein modifying tasks. The number of such protein modifying enzymes in the proteomes of humans is fairly large. For example, 500 protein kinases, 150 Protein phosphatases, 500 proteases, more than 100 ubiquitin ligases and more than 50 deubiquitylating enzymes. In total, between 1000-2000 genes, representing more than 5% of the human genome, may encode enzymes dedicated to protein modifications.

There are two separate activities for this course; the first is a weekly 50-60 minute lecture where research concepts will be presented by the instructor followed by additional 50-60 minute discussion of an assigned paper related to that particular topic presented by a student.

Exams: There will be a midterm and a final exam. Both exams will consist of short essay responses to questions from the lectures and discussion presentations.