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MPM1 Chromosome, Gene and Defective DNA Repair Disorders

Many diseases are the result of gross chromosomal rearrangements or genetic lesions, often resulting from defects in the repair and maintenance of our genetic material. This module will develop a deep and mechanistic understanding of how DNA is faithfully replicated and repaired, how and where these lesions typically arise, and what their consequences are. Paradigmatic diseases will be used to illustrate what can go wrong, how defective repair manifests itself in disease, and therapeutic strategies.


Module overview

In Module 1, we will start with the fundamentals of how our genetic code is organized, transcribed, replicated and faithfully segregated during multiple rounds of somatic cell division. We will examine the molecular basis for DNA repair pathways including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and DNA double-strand break repair via non-homologous end joining (NHEJ) or homologous recombination (HR). The role of defective DNA repair in genetic predisposition to cancer by increasing the mutational burden, as well as the mechanistic basis of chromosome instability syndromes and disease caused by defective DNA damage signaling will also be examined.

Diseases associated with defects in DNA repair pathways will be used to illustrate the molecular mechanisms of pathogenesis. We will learn how chromosome-level lesions occur and in which cell types. We will investigate the mechanistic basis of diseases caused by chromosomal translocations that drive over-expression of a gene locus as well as those diseases driven by gene amplification. We will examine chromosomal translocations that drive expression of a protein product with altered, pathological behavior. Finally, we will study the role of chromosomal instability (CIN) and aneuploidy in cancer, as well as therapeutic approaches to target CIN.

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. State-of-the-art concepts in therapeutic intervention will be examined with respect to paradigmatic diseases. We will cover the concept of synthetic lethality, develop a molecular understanding of how pathological protein products can be targeted for disease treatment with high specificity, and examine approaches to ‘drug the undruggable’, including the challenges and limitations of these approaches. Our goal is to understand that treatments should be guided by the molecular cause of disease.

Teaching faculty include basic research scientists from the Max Perutz Labs, the Medical University of Vienna, the Center for Molecular Medicine, the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, the Boehringer Ingelheim Institute for Molecular Pathology, Johannes Kepler University, and the University of Veterinary Medicine Vienna. Clinicians from the Medical University of Vienna and St. Anna Children’s Cancer Research Institute. Guest lecturers will complement the program with pharmaceutical industry and biotech perspectives.


Module coordinators

Christopher Campbell

Christopher Campbell is an Associate Professor at the Max Perutz Labs (University of Vienna). His research focuses on mechanisms that promote accurate chromosome segregation and how cells adapt through the accumulation of aneuploid chromosomes.

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Joanna Loizou

Joanna is an Associate Professor at the Medical University of Vienna and an Adjunct Principal Investigator at the Austrian Academy of Sciences Centre for Molecular Medicine (CeMM). Her research focuses on the mechanisms by which cells respond to and repair DNA damage to maintain genomic stability, with a strong emphasis on tumorigenesis and rare hereditary diseases.

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