Presence of insoluble protein deposits in human tissues correlates with the development of over 100 human disorders, known as amyloidoses. Presence of amyloid deposits in the brain is a major characteristic of patients with neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's disease, transmissible spongiform encephalopathies, and amyotrophic lateral sclerosis.

In the last decades, a lot of effort has been put into exploration of the amyloid phenomenon. Molecular basis of amyloid formation and amyloid-induced toxicity are the two most challenging questions for today's neuroscientists.

In order to monitor the molecular processes which occur as a response to amyloid aggregates in the complex and crowded milieu of the cell, yeast Saccharomyces cerevisiae has already been used successfully. S. cerevisiae has served as a model of a eukaryotic cell to analyze the molecular mechanism of pathobiology of two amyloidogenic proteins, α-synuclein and huntingtin (Science (2003) 302:1769). This study identified evolutionarily conserved and nonoverlapping sets of genes and pathways that might be relevant to the development of corresponding diseases.

We plan to identify genes and molecular pathways affected by amyloidogenic proteins in eukaryotic cells by observing the changes upon introducing our model protein, stefin B, into S. cerevisiae cells. To accomplish these goals we will follow the response of S. cerevisiae (i) by monitoring the gene expression pattern after induction of stefin B expression and thus triggering its intracellular activity, and (ii) by determining the genetic interactions of stefin B encoding gene with the S. cerevisiae genome. Bioinformatics analysis will subsequently be used to infer the molecular mechanism of the biological activity of protein aggregates in a eukaryotic cell.