Genetic variation in protein synthesis and abundance

• Applicant: Professor Dr. Frank Albert
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 213952200

DNA variation between individuals is the substrate of evolution and influences susceptibility to many human diseases. Because some DNA variants exercise their effects on the phenotype by influencing gene expression, a common research strategy is to directly search for variants that affect the expression level of one or several genes. Although genes exercise their functions though their protein products, most such studies so far have focused on intermediary molecules, rather than on the proteins themselves.Here I propose to investigate the role of genetic variation affecting protein expression in genetically different strains of the yeast Saccharomyces cerevisiae. First, I will adapt a recently developed genetic mapping strategy to identify DNA variants influencing protein levels. I will repeatedly cross one genetically different yeast strain to a collection of yeast strains where every protein gene has been linked to a green fluorescent protein so that the intensity of green fluorescence in a cell is a measure of protein abundance. By comparing DNA from offspring with high to those with low protein abundance, genetic variants causing differences in protein expression can be identified.Second, I will study the influence of genetic variation on translation. During translation, ribosomes read mRNA molecules and translate them into proteins. Translation is thought to be the major determinant of protein levels. I will compare translation in yeast strains by using ribosomal footprinting, where mRNA fragments that are read by ribosomes are quantified. I will then search for genetic variants influencing translation using a cross between two strains of yeast. Together, these approaches will provide a detailed view of how genetic variation influences protein levels and production. The mechanisms that this work will reveal may apply to other species, and may have relevance for human disease.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Leonid Kruglyak