Signal transduction is the study of how cells control their own and each other's behaviors through physical (light, sound) or chemical (hormone, neutrotransmitter) signals. Signal transduction research is an intensely active field of research, and UNH faculty are engaged in a variety of research programs that employ biochemical, molecular, cellular, and genetic/genomic approaches to understand cellular communication.
Feixia Chu — Epigenetics of histone post-translational modifications
Chromatin, the complex of genomic DNA and its associated proteins, constitutes the converging focus of various signaling pathways, and its structure defines the inheritable identity and fate of the cell. Histones are major chromatin proteins that are responsible for packaging genomic DNA into higher-order structures. Modifications of histone proteins can regulate effector protein binding or directly modulate chromatin structure, hence playing an important role in mediating various cellular responses to environmental influences. Using quantitative mass spectrometry, the Chu lab is capturing a panoramic view of the histone epigenetic “landscape,” and how it changes dynamically in response to cellular signaling processes such as differentiation and the DNA damage response. The functional significance of histone modifications during specific cellular processes are also being independently approached from both biochemical and cell biological perspectives.
Rick Cote — Visual transduction pathway in retinal rod and cone photoreceptors
Rick Cote’s lab studies the visual signaling pathway in retinal rod and cone photoreceptors, focusing on the regulation of photoreceptor phosphodiesterase (PDE6) during light activation of the phototransduction cascade. The experimental tools we rely on include a variety of molecular, enzymological, and cell biological approaches, along with collaborations with the Thomas laboratory (structural genomics of PDEs), with the Chu laboratory (proteomic discovery of the PDE6 protein "interactome"), and with the Laue laboratory (biophysical approaches to PDE6 structure/regulation). Ultimately, our biomedical research will contribute to the development of therapeutic approaches to intervene in retinal diseases.
Clyde Denis — Protein translation complexes
The research in Clyde Denis' lab concerns deciphering the mechanisms by which environmental stresses control mRNA translation and stability. Stress conditions, such as starvation, high temperatures, and excessive UV radiation, commonly lead to cessation of protein synthesis, an adaptation critical to eukaryotic cell survival. In studying the yeast, Saccharomyces cerevisiae, we are examining how particular stresses affect protein translation complexes by different mechanisms and lead to the formation of stress granules, the site where quiescent mRNA complexes are often held until conditions improve. Using the novel technique of analytical ultracentrifugation with fluorescent detection system (AU-FDS) (research conducted in collaboration with the Laue laboratory), we have been able to detect specific translational complexes present in complex mixtures. AU-FDS allows us to discriminate between stress conditions that alter protein phosphorylation patterns and those that involve stress granule formation. Moreover, by conducting mass spectrometeric studies on these protein complexes (in collaboration with the Chu laboratory (UNH)), we intend to identify how enviornmental effects alter protein interactions in order to control protein synthesis.
Estelle Hrabak — Signal transduction in Arabidopsis: regulation by post-translational modifications
Estelle Hrabak's lab uses genetic and biochemical approaches to study enzymes involved in signal transduction in plants. Our primary study organism is Arabidopsis thaliana. The two major projects in the Hrabak lab focus on protein phosphatases and palmitoyltransferases; both enzymes are encoded by large gene families in Arabidopsis. Protein phosphatase 2A (PP2A) is known to regulate many hormone response pathways in plants and likely has other functions as well. For example, using a reverse genetic approach, we found that some pp2a mutants have altered responses to sodium stress. Currently, we are dissecting the cellular and subcellular basis of this mutant phenotype. Palmitoyltransferases (PAT) are integral membrane proteins that acylate their substrates by covalent attachment of the fatty acid palmitate. Acylation can have major effects on the subcellular localization, half-life, or activity of the substrate proteins. We are interested in identifying the substrates of PATs, determining in which cellular membrane(s) each PAT resides, and characterizing the phenotypes of pat mutants. The long-term goal of our research is to thoroughly understand basic biology of plants for application to biotechnology or agriculture.
Stacia A. Sower — Molecular mechanisms of neurohormone interactions with G-protein-coupled receptors
Using molecular, anatomical, cellular, and systems biological approaches, the Sower laboratory seeks to understand how modifications in cellular signaling networks — represented by genes, hormones, receptors, and other signaling molecules — act on biological and reproductive functions. Reproduction in all vertebrates is regulated by gonadotropin-releasing hormone (GnRH). In the anterior pituitary, GnRH’s action is mediated via the GnRH receptor, a class A (or rhodopsin-like) seven transmembrane segment G-protein-coupled receptor (GPCR). The presence or absence of the C-terminal tail in the type-II or type-I GnRH receptors, respectively, results in differences in receptor functional organization and in the mechanism of signal termination (mediated by agonist-induced phosphorylation, desensitization and internalization). The Sower group is examining the molecular mechanisms of GnRH receptor binding and signaling using site-directed mutagenesis, pharmacological profiling, identification of binding and activating sites, and characterization of downstream signaling pathways.
Paul Tsang — Female reproductive physiology
Paul Tsang's lab studies female reproductive physiology using the sheep, cow and fish animal models. The varieties of experimental tools we use include whole animal, cellular, molecular and cell culture approaches. In sheep, we study the molecular mediators of corpus luteum regression initiated by prostaglandin F2 alpha (see accompanying cell model). In the cow, we are profiling the molecular medators associated with the angiogenic switch that occurs in the ovarian follicle and the corpus luteum. In sharks and skates, we study the life history of these elasmobranchs, including reproduction, age and growth and poupulation structure. Our collaborators include John McCracken (sheep; University of Connecticut), Marsha Moses (cows; Children's Hospital Boston) and James Sulikowski (sharks and skates; University of New England). Ultimately, our research has applications in biomedicine (infertility and cancer) and in fishery management.
Cheryl Whistler — Transition of bacteria from the planktonic to the host lifestyle
The Whistler lab is investigating hierarchical signal transduction systems that trigger the transition of certain bacteria from the planktonic to the host lifestyle. During host colonization, bacteria must coordinate a number of traits in order to overcome host defenses and establish an infection. To do this, they sense signals from their environment and then appropriately regulate gene expression. A number of bacterial species utilize a classical two-component signal transduction system comprised of the GacS sensory kinase and the GacA response regulator. Interestingly, this signaling system can result in either disease or establishment of a beneficial symbiotic association. We are characterizing the transcriptional and translational regulatory mechanisms by which GacS/GacA governs the ability of bacteria to activate genes by cell density in response to chemical pheromones (quorum sensing). In addition, research is directed at understanding how changes in temperature of the host induces a transition to the pathogenic state. Our lab is also focusing effort on how symbiosis and virulence are regulated by complex gene networks through use of whole genome transcriptomics and proteomics approaches. Our goal is to understand how bacteria integrate horizontally acquired colonization genes within these ancient regulatory networks in order to adapt to new environments.