Cullen, Gokcumen, Medler, and Yu win grants from NSF and NIH

Control of MAPK Signaling by Cell Polarity Proteins

Dr. Paul Cullen continues the project he began in 2011, Control of MAPK Signaling by Cell Polarity Proteins. The project is supported by The National Institute of General Medical Sciences. This grant funds the long-term goal of defining the MAP kinase pathway that regulates filamentous growth in yeast. The pathway is composed of a mucin sensor that regulates the ubiquitous Rho GTPase Cdc42. Cdc42 and an associated scaffold regulate the activity of four kinases in a tandem series that ultimately regulate the transcriptional response underlying filamentous growth. Most of the components are highly conserved in structure and function throughout evolution, which provides a convenient model for understanding the mechanisms that control differentiation (ERK-type) MAP kinase pathways. Filamentous growth itself is a morphological response to nutrient limitation in fungi and occurs in many species, including pathogens, which can cause disease by virtue of homologous signaling machinery. Therefore, understanding how mucins, Rho GTPases, adaptors and kinases regulate filamentous growth can provide insight into MAPK pathways in general and mechanisms that contribute to fungal pathogenesis.​

Salivary proteome evolution as a framework to elucidate the mechanisms of functional change involving genomic structural variation

Dr. Omer Gokcumen's project description: Evolution underlies the amazing diversity in life. Understanding the specific mechanisms through which evolution operates will help understand how new traits, abilities, and forms emerge. Saliva can serve as an ideal candidate for studying such evolutionary changes because it acts as the first interface for food, microorganisms, and other foreign molecules entering our bodies. This project will explore how new genes evolve and how they affect salivary function. It will do so by comparing the genetic variation, gene expression levels, and protein content of diverse mammalian species, focusing on salivary function. The results of this project will shed light on fundamental questions about how evolution operates, how new genes are formed, how their functions change over time, and why the properties of saliva vary this much among mammals. The state-of-the-art approaches that will be used in this study will be disseminated to a diverse group of graduate students from different institutions through a hands-on workshop. Additionally, the research team’s efforts include hosting the annual Great Lakes Evolutionary Genomics Symposium, hosting more than 100 trainees and faculty interested in evolutionary genomics. The project will serve as a platform for the research team to engage with the public, promoting STEM training and evolutionary biology at both the national and international stage.

Characterizing the role of TRPM4 in taste transduction

Dr. Kathryn Medler’s project concerns the role of TRPM4 in peripheral taste transduction. As Dr. Medler describes it, "Our sense of taste is critical for survival, and taste stimuli activate multiple signaling mechanisms in diverse taste cell populations within the oral cavity, including both GPCR pathways and ionotropic pathways.  We discovered that the monovalent selective TRP channel, TRPM4, has a critical role in the normal transduction of stimuli using GPCR signaling and new data suggests it has a critical, but distinct, role in ionotropic signaling. The goal of this grant is to determine how TRPM4 selectively contributes to taste transduction in these different signaling pathways in taste cells."

Elucidating the role of protein arginine methylation in regulating RNA-binding protein function

Dr. Michael Yu’s project description: In eukaryotes, many RNA-binding proteins harbor protein arginine methylation. This post-translational modification is catalyzed by a family of evolutionarily conserved enzymes known as protein arginine methyltransferases (PRMT). Genetic studies have revealed that protein arginine methylation contributes to the function of RNA-binding proteins, but it is not clear how this post-translational modification is regulated, and what the biological consequences of such regulation are. This project will address these questions by studying a model RNA-binding protein (called Npl3) in the budding yeast Saccharomyces cerevisiae. Npl3 is methylated on arginines by the major PRMT enzyme in yeast. When methylated, Npl3 promotes splicing of pre-mRNAs that function at different times in the growth cycle. The goals of this project are to examine the molecular mechanisms by which protein arginine methylation in Npl3 is regulated and the consequences of such regulation at both molecular and cellular levels. A multi-faceted approach using molecular biology, biochemistry, proteomics, and genomic technologies will be utilized to carry out these studies. The outcomes are expected to improve our understanding of the dynamics of protein arginine methylation and its effects on cellular adaptation to growth under different environmental conditions.