The research in the lab breaks down roughly into the following areas:
Genetic basis of quantitative variation in signaling pathways
Understanding the genetic basis of phenotypic variation is an important goal of systems biology. With recent technology, it has become relatively straightforward to sequence an entire genome. However, even with this information it is still unclear how the functions of many genes combine to give rise to the behavior of a pathway, let alone the phenotype of an entire cell or organism. We know that mutating genes in a pathway will affect the pathway’s output or ability to function, but what about mutations outside the pathway? How robust are pathways to mutations elsewhere in the genome? How are quantitative features of a pathway affected by variation in the underlying genes, and how does natural selection fine-tune these traits? We are trying to answer these questions with two approaches: 1) constructing pathway-specific fluorescent protein reporters to monitor pathway activity in single cells at high time resolution; 2) performing high-throughput phenotypic profiling for large collections of yeast strains isolated from different ecological niches. Together, the results of these projects will help us to better understand the physiological consequences of genetic variation, as well as the evolutionary forces that create and maintain this variation.
Evolutionary trade-offs in metabolism
Theoretical and experimental studies have suggested that complex environments with multiple limiting nutrients will generate different strains that optimally utilize each nutrient. These studies assume a trade-off between metabolizing one nutrient versus another. It is also possible that instead of various specialist strains arising, one generalist strain will appear that benefits when grown on multiple nutrients. To assess what trade-offs may govern the origin of new species, we aim to conduct an experimental evolution study by growing yeast strains in a variety of carbon sources. We will determine the occurrence of specialist versus generalist strains by massive phenotyping in different nutrient sources and will uncover their underlying genetic adaptations via high-throughput sequencing.
Duplicate genes in signaling networks
Gene duplication generates genomic redundancy that can buffer cellular responses. It may also relieve the selective constraints on a gene, enabling it to acquire mutations that would otherwise be deleterious. Previous studies have explored the differential regulation of duplicate genes at the expression level, but little is known about how post-translational modifications have evolved among duplicate genes. We aim to explore this topic by selecting pairs of duplicate genes in budding yeast and profiling these modifications in relevant conditions using mass spectometry. We hope to determine how these modifications contribute to the new roles that genes acquire after their duplication.