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MPM3 Diseases of Enzymatic Insufficiency

Many diseases are the result of enzymatic insufficiency. This module will develop a deep and mechanistic understanding of enzyme function, including those involved in drug metabolism, as well as the role of pharmacogenomics in precision medicine. Paradigmatic diseases will be used to illustrate the diagnosis, manifestation, molecular etiology and precision treatment of enzymatic insufficiencies.


Module Overview

In Module 3, we start with the fundamentals of enzymology, including the production, processing, and utility of proenzymes. We will cover sugar, nucleotide, and lipid metabolism, as well as haem biosynthesis. In a link to module 2, we will discuss the disposal and recycling of cellular components by enzymatic degradation in lysosomes. We will examine drug metabolism at a molecular level and investigate the role of pharmacogenomics in treatment regimens.

In terms of disease, we will examine the differences between monogenetic and multigenetic diseases, visit the concepts of haploinsufficiency and dominant negative effects in genetic disease and discuss the accumulation of toxic intermediates in metabolic disease. We will examine the coagulation cascade at a molecular and mechanistic level with a focus on pathogenic mutations that give rise to a wide range of blood clotting disorders. We will also focus on the structure-function relationship and how this can be used to rationalize disease-associated mutations. Students will be familiarized with patient clinical presentation, diagnosis, treatment strategy, clinical outcome, and future perspectives alongside a deep and mechanistic understanding of the disease itself.

We will develop a global view of the current technologies to treat diseases caused by enzymatic insufficiencies including the development of small molecule inhibitors, therapeutic strategies to modulate enzymatic activity, production and treatment with recombinant proteins, novel RNA interference therapeutics, adenoviral gene therapy, and genome editing.

Teaching faculty include basic research scientists from the Max Perutz Labs and the Medical University of Vienna, as well as clinicians from the Medical University of Vienna.


Module coordinators

Javier Martinez

Javier Martinez is Professor of Inflammation Biology at the Max Perutz Labs (Medical University of Vienna). Javier’s research group is interested in the enzymes that control RNA processing and their roles in cellular metabolism and human disease.

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Sabine Eichinger

Sabine Eichinger is a Professor and Haematologist at the Medical University of Vienna. Sabine specializes in the treatment of cancers of the blood and coagulation disorders such as haemophilia. In addition to being a practicing clinician, Sabine has an active basic research programme with a focus on blood clotting disorders.

Website