Genetics Research Faculty
Gene expression patterns in Staphylococcus aureus
Low G+C Gram-positive bacteria, including Staphylococcus aureus, are metabolically versatile and can interact with hosts in diverse ways. They can reside in and on our bodies in a commensal state or can cause life-threatening infections. Genetic switches, controlled in part by transcription factors that bind key intracellular metabolites, govern the reconfiguration of physiology that mediates the shift between commensal and pathogenic lifestyles. Despite observations that the expression of virulence genes often correlates with the exhaustion of available nutrients, there is limited knowledge about how the signaling of nutrient status and the resulting physiological responses are coordinated.
We are studying the integrated regulation of metabolism and pathogenesis in S. aureus, an important hospital- and community-acquired infectious disease agent responsible for significant morbidity and mortality. We are currently examining in depth the role of the global regulatory protein CodY in altering the activities of multiple metabolic pathways when faced with changing levels of nutrient depletion, and how this response is coupled to the production of virulence factors. A deeper understanding of cellular mechanisms underlying bacterial disease will reveal new ways to prevent the switch from harmless to harmful lifestyles that lead to potentially life-threatening infections.
Elena Casey, see Elena Silva
I am deeply intrigued by the processes that influence the distribution of genetic variation within species. My empirical projects focus on either marine fish populations or plant populations. Research in my laboratory focuses on fundamental questions in evolutionary biology, population genetics and conservation genetics. I am interested in gene flow and population structure, the interplay of effective population size and natural selection, and inferring population demographic histories from genetic data. I frequently use simulation modeling to develop expectations for the behavior of genetic systems under idealized evolutionary processes. My lab also employs molecular genetic methods such as microsatellite genotyping and DNA sequencing to estimate key population genetic parameters such as effective population size, degree of population structure and rates of gene flow.
Research in my laboratory is focused on elucidating the mechanisms that yeast cells use to sense external conditions – such as nutrient abundance and host status – and how these cells alter gene expression in response to these conditions. We are studying the metabolism of and roles for inositol pyrophosphates in Saccharomyces cerevisiae. In Candida albicans, we are investigating how filamentation is controlled at the genetic level.
My laboratory is focused on two major areas of cell biology – cell fusion and the control of meiosis. Many of the genes required for cell fusion and meiosis have close homologs in all eukaryotic organisms; it is likely that their functions are deeply conserved.
Cell Fusion: One of the most fundamental events in eukaryotic biology is the fusion of two cells to produce a single cell. Although fertilization is the basis of sexual reproduction, cell fusion also plays important roles during development. For example, muscle fibers are formed by the fusion of precursor cells. We are using the yeast Saccharomyces cerevisiae to identify genes and proteins responsible for the two major steps in mating; cell fusion and nuclear envelope fusion.
Control of Meiosis: Recent work from many laboratories has revealed the complexity of the regulation of meiosis. My lab is actively studying how one key regulator, Kar4p, affects both transcriptional and translational regulation during yeast meiosis.
Protein Trafficking and Ion Homeostasis
The Rosenwald laboratory investigates a number of different aspects of life at the microbial level, including membrane traffic, cell wall biosynthesis, and ion homeostasis in Saccharomyces cerevisiae (Baker’s yeast) and its close, but pathogenic relative, Candida glabrata. We use approaches that combine classical techniques of biochemistry, cell biology, and genetics, but more recently have also included bioinformatics and genomics in our arsenal of tools.
Neural induction in Xenopus laevis
The goal of the Casey lab is to understand the transcriptional regulation of a class of genes involved in the formation of the early vertebrate body plan. Patterning events such as the establishment of neural tissues require a series of signal transduction events that lead to the transcription of a set of genes. Few of the details of transcriptional regulation in vertebrate development have been deciphered. However, the ability to generate transgenic frogs has revolutionized the field, allowing rapid analysis of promoter function in a large number of embryos. This technique, along with embryology, traditional biochemical and molecular assays, and expression screens now enable us to define the factors required for regulation of genes involved in early vertebrate development.
My research seeks to discover general rules that govern arthropod community structure that may serve as tools for conservation. I have found that plant genetics plays a critical role in shaping arthropod community structure, but the extent to which plant genetics affects higher-level trophic interactions remains a topic of debate which I am pursuing. My research also focuses on the role of anthropogenic disturbance and habitat fragmentation on arthropod community structure in inter-tidal marshes. I am using stable isotope analysis to understand how arthropod species losses in the inter-tidal marsh may affect nutrient cycling in these critical ecosystems that act as buffers to adjacent estuaries. Arthropod conservation has not received the same consideration as vertebrate species conservation, yet arthropods represent over half of the described species on the planet and their losses could have cascading effects throughout diverse ecosystems.