Yeast as a model for human neurodegenerative diseases

 




This project is carried out in the group of Systems Biology.


Neurodegenerative diseases are fatal and incurable conditions caused by neuronal cell loss. As the world population ages, the incidence of neurodegenerative diseases is dramatically rising, posing a growing burden on the patients, their families and broadly on society. For example, it is estimated that 26.6 million people suffer from Alzheimer’s disease (AD), and in 2012 this was the 6th cause of death in USA. The search for the cure that would prevent, slow or revert AD is a tedious process, because the pathologies of the brain and neuron cells are complicated to study.


In order to study the cellular and molecular mechanisms that are involved in onset and progression of AD, scientists use different model systems in laboratory, such as cells in culture, mammals (mouse or rat), flies, worms, fish etc. Among the favorite model organisms is yeast, Saccharomyces cerevisiae that we also use in the lab to study human proteins involved in AD.


Yeast has several clear advantages for cell and molecular biology research, and in many occasions molecular biology of yeast has led to discovery of proteins, regulations and drugs that are of relevance, and in use for treatment of human diseases. In my lab we study cellular pathways that are relevant for development of AD and similar diseases that are caused by protein stress and subsequent cell death.

 

 

Why study neurodegenerative diseases?
Neurodegenerative diseases, specifically neurodegenerative proteopathies (protein conformation diseases) include several different pathologies, which are all deadly and incurable diseases that affect mostly people above age 65. According to the recent report from United Nations, the aging phenomenon is unprecedented in human history, global and irreversible. To quote from the same report: “The number of older persons has tripled over the last 50 years; it will more than triple again over the next 50 years” (World Population Aging 1950-2050, Catalogue of United Nations Population Division, 2003). Alzheimer’s Disease (AD) is the most common dementia and proteopathy and to quote another recent international report on AD and its implications: “We face a looming global epidemic of Alzheimer’s disease as the world’s population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in Alzheimer’s onset and progression can significantly reduce the global burden of the disease” (Forecasting the Global Burden of Alzheimer’s Disease: Johns Hopkins University, 2007). It is clear from these and other reports that if we want to be ready to face the epidemic that is already progressing, we need research to understand what causes the disease, what influences its onset and progression and with that, how we will create drugs and treatments that will prevent, cure or alleviate these diseases.


Why use yeast to study neurodegenerative diseases?
Yeast S. cerevisiae is one of the best model organisms for study of eukaryal cell biology and it is especially useful as a model when cellular processes, molecular pathways, proteins functions and genes are conserved evolutionary (from yeast to other model organisms such as worms and flies, and also to humans). Furthermore, there is a broad range of molecular tools that allow genetic and environmental manipulations (mutations, deletions or overexpressions in the chromosome or extrachromosomally on plasmids) and screening. Additionally, many novel “omics” methods are suitable for S. cerevisiaeand the integration of the data generated using systems biology approach allows the study of complex regulatory networks such as those involved in aging and cell death. In particular S. cerevisiae has a long tradition of being used to study molecular mechanisms relevant for human health and it has been used for study of molecular mechanisms such as DNA replication, recombination, transcription, protein biosynthesis, proteostasis, respiration and stress response. For example, yeast can be also used to express human genes (so-called humanized yeast) and thus human proteins (and their interactions, folding, influence on cell homeostasis or stress) can be studied in a simplified model that can provide useful insights. In addition, we are also using modeling and bioinformatics approach to integrate data, simulate cell behavior and learn about cellular regulations that are of relevance for cell damage and death.
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Published: Wed 06 Mar 2013. Modified: Thu 19 Jul 2018