Grant: Discovery Grants Program - Individual

The overall goal of the research program in my laboratory is to achieve a better understanding of how gene expression is regulated, resulting in the synthesis of proteins from mRNA molecules. Protein synthesis, also known as translation, is an essential requirement for the survival of a cell, and the cellular machinery responsible for translation is highly conserved throughout the course of evolution. Translation control is used to regulate the expression of a variety of mRNAs under different physiological conditions such as cell transformation, stress, and apoptosis. Abnormalities in translation have been linked to pervasive human conditions such as cancer and diabetes, among others. My laboratory is particularly interested in identification of mechanisms and novel factors that affect protein synthesis, as well as the regulations and cross-communications between different cellular processes that govern protein synthesis. For this, we use the model prokaryotic and eukaryotic organisms Escherichia coli, and the baker's yeast, Saccharomyces cerevisiae, respectively. In the upcoming grant period, we propose to build on our previous work and to investigate how a eukaryotic translation initiation region can function in prokaryotes. We are also interested in studying the influence of an mRNA binding protein Dom34 on non-standard (mRNA cap-independent) eukaryotic translation initiation. mRNA recognition and binding to mediate translation initiation is one of the most notable differences between prokaryotic and eukaryotic translations. In a recent study, it was illustrated that prokaryotic and eukaryotic mRNA recognition and binding may not be as distinct as previously thought. The authors showed that a non-standard eukaryotic Internal Ribosome Entry Site (IRES) can mediate alternative translation initiation in prokaryotes. Using E. coli as a model system, we plan to study the mechanism of prokaryotic translation initiation mediated by this eukaryotic signal. This is an important evolutionary question and can significantly impact our current understanding of the field at a mechanistic level. In addition, we have previously shown that the mRNA binding protein Dom34 can influence the activity of certain IRESs. We also plan to further investigate the activity of Dom34 as a general regulator of cap-independent protein synthesis in yeast. Establishing Dom34 as a novel regulator of IRESs that may function indiscriminately will be a very interesting finding as it is generally accepted that different IRESs require different regulators. Our expertise in large scale genome-wide studies and approaches will further enable us to identify factors that influence certain IRES mediated translations in both prokaryotes and eukaryotes.