Research Project Internal Grant Funding

Grants from the Center for Molecular Communication and Signaling (CMCS) are intended to foster interdisciplinary collaboration, to catalyze and support research, to promote the training of new researchers in the area of molecular communication and signaling, and to develop new approaches and research directions in this area. When open, call for proposals are listed here.

Funded Proposals


Bruce King, Chemistry Department: Nitrogen Oxide formation from Nitroimidazole Antibiotics

Tom Hollis, Leslie Poole, Joelle Muhlemann, and Gloria Muday, Departments of Biochemistry and Biology. Exploring SamHD1 oxidative regulation and function in controlling the cell cycle in Arabidopsis. (cofunded by CBRM)


K-mer Analysis of Peroxiredoxin Classes and Subgroups
William Turkett, Computer Science and Leslie Poole, Biochemistry

Mechanosensing in the Maintenance of Genome Integrity
Keith Bonin, Physics and Pierre Vidi, Cancer Biology

Exploring the Therapeutic Potential of Spilanthol in Chlamydia Infection
Heather Brown-Harding, Biology, Allen Tsang, Internal Medicine

May 2017

Intramolecular and intracellular signaling by a tRNA base modifying enzyme
Rebecca Alexander, Chemistry

Abstract: The goal of this project is to understand the connections between tRNA base modification, genetic code accuracy, and cellular fitness. We will use as our model system tRNA isoleucine lysidine synthetase (TilS), the bacterial enzyme that catalyzes a single anticodon base modification to ensure the rare AUA (isoleucine) codon is properly decoded. Surprisingly, experimental evolution of the opportunistic pathogen Burkholderia cenocepacia in minimal media selected mutations to TilS and tRNAIle2 that increased bacterial fitness. Given the presumed requirement for high translational fidelity, these spontaneous mutations provide an opportunity to investigate genetic code accuracy at both the molecular and cellular levels. Funding provided by the Center for Molecular Signaling and the Center for Redox Biology and Medicine will enable us to investigate the kinetic and dynamic features of TilS variants using biochemical and computational approaches. We will also further characterize the fitness advantage provided by these variants under oxidative stress conditions. This work is a collaboration with Dr. Vaughn Cooper (U. Pittsburgh School of Medicine), Freddie Salsbury (WFU Physics), and James Pease (WFU Biology).

Probability density analysis to quantify polarity signals in breast acini
Keith Bonin, Physics and Pierre Alexander Vidi, Cancer Biology

Abstract: The goal of this project is to develop an image analysis software for the quantification of cell polarity in 3D culture models of the breast epithelium. Apical-basal polarity of epithelial cells is key to homeostasis and is one of the first tissue characteristics lost during cancer initiation. Mammary gland units (acini) with apical-basal polarity can be produced in 3D culture. In this system, polarity is quantified based on localization of markers, such as cell-cell tight junction (TJ) proteins. This project supports an independent student research project. The student will (1) improve a software (developed with prior CMS support) by integrating a batch function and improved image segmentation for fully automated analysis of large image datasets; (2) implement in the code a probability density function (PDF) to increase precision and versatility in polarity quantification, and (3) establish a cell line with a genetically encoded reporter of TJ localization to gain temporal resolution in the analysis of cell polarity. The anticipated outcome of the project will be a platform for rapid, cost-effective assays of epithelial polarity, with future applications including screening compound libraries for chemoprevention and rigorous evaluation of risk reduction in cancer prevention trials. The project is designed as an educational experience balancing theoretical physics, programing, and cell biology.

Mechanosignaling in the maintenance of genomic integrity
Keith Bonin (WFU Physics Department) and Pierre Vidi (Cancer Biology)

Abstract: Women with high mammographic density are at increased risk to develop breast cancer. High mammographic density reflects higher tissue stiffness. It is however largely unknown why this physical property of the breast is associated with increased cancer risk. Our hypothesis is that breast tissue stiffness influences DNA repair mechanisms, which are essential for tumor suppression. Specifically, we propose that the stiffness of the cell environment regulates how efficiently cells detect DNA damage, and/or the dynamics of chromatin, which is thought to be an important aspect of DNA repair. To test this hypothesis, we will implement a novel microscopy platform to simultaneously irradiate (with X-rays) and image live breast epithelial cells in soft and stiff environments. We will track early events of the DNA damage response as well as chromatin motions when DNA damage is generated and repaired. The significance of the proposed research is its potential to uncover a mechanistic link between high breast stiffness and genomic instability, with future implications for cancer prevention. The broader impact of this application includes training of two undergraduate students for computational image analyses and cell-based assays.

The effect of drugs of abuse on brain cholesterol content and the membrane compartmentalization and signaling of G proteins
Rong Chen, Physiology and Pharmacology and Glen Mars, Biology

Red Blood Cell Mediated Nitrite Signaling in Diabetes
Dany-Kim Sharpiro and Nadeen Wajih, Physics

Abstract: Prior to our work, nitrite was thought to be biologically inert.  However, we have shown that nitrite increases blood flow through formation of the important signaling molecule nitric oxide (NO) under hypoxic (low oxygen) conditions.  NO has been shown to vasodilate; inhibit platelet activation and aggregation; decrease adhesion of circulating blood cells; protect against ischemic reperfusion injury; and generally decrease inflammation and protect against oxidative damage under certain conditions. We hypothesized that nitrite serves as a storage pool for nitric oxide that is harnessed by a new function of hemoglobin when it is deoxygenated.  However, this hypothesis is challenged by the fact that NO is scavenged rapidly by hemoglobin, suggesting NO activity cannot be exported by the red blood cell (RBC).  Recently, we have found new evidence of how NO activity is exported from the RBC that involves nitrosation of RBC surface proteins.  We also found that nitrite bioactivation by RBCs is blunted by high, but physiologically relevant concentrations of glucose.  In this project we will define the precise mechanisms of RBC-mediated bioactivation of nitrite and its blunting by glucose.  Many pathological conditions are partially caused by low NO bioavailability and/or would benefit from administration of NO including diabetes.  Our work will define a novel biochemical pathway that (hopefully) will be described in basic textbooks one day as well as impact nitrite therapeutics in a variety of diseases including that focused on here, diabetes.

Are TRP channels involved in earth worm chemisthesis
Wayne Silver, Biology

January, 2016

Minigrants for small projects:

Enrichment and Quantification of SAM Analog Modified Histone H4
Lindsay Comstock-Ferguson, Chemistry, $800

Elf1 ensures genome stability in fission yeast
Ke Zhang, Biology

Muscular Signaling Systems and the Evolution of Physically Elaborate Behavioral Displays
Matt Fuxjager, Biology

Prostate Cancer Targeted PI3 Kinase Inhibitors
Mark Welker, Chemistry; George Kulik, Cancer Biology: Fred Salsbury, Physics

A MATLAB routine to quantify leptin-mediated polarity loss in 3D cell culture models of breast acini
Keith Bonin, Physics; Pierre Vidi, Cancer Biology

Visualization of Cytoskeletal Components to Identify Fate of Neurites Induced by Overexpression of Cannabinoid Receptors
Glen Marrs, Biology; Allyn Howlett, Physiology and Pharmacology

FRET Analyses of RGS2-Interacting Proteins
Erik Johnson, Biology; Rong Chen, Physiology and Pharmacology

Studies of Signaling-Related Protein Oxidation Through CRISPR-Mediated Knockouts
Bruce King, Chemistry; Leslie Poole, Biochemistry

January, 2015

The detection of chemical irritants in earth worms: Are TRP channels involved
Wayne Silver, Biology

Regulation of Pombe cell division through regulation of peroxiredoxin activity and cysteine Oxidation
Ke Zhang, Biology and Kim Nelson, Biochemistry

January, 2014

Dissection of Nutrient Sensing Mechanisms by Central Neurons in Drosophila that Govern Reproduction
Erik Johnson, Biology; Robert Newman, NCA&T

CB1 cannabinoid and D2 dopamine Receptor Signaling as Neuronal Progenitors Differentiate
Glen Marrs, Biology, Allyn Howlett, Physiology and Pharmacology, Rong Chen, Physiology and Pharmacology

Probing Biological Phosphorylation through Cofactor Mimicry
Lindsay Comstock

June, 2013

Regulation of steroid hormone titers in adult worker honey bees by a pheromone signal
Susan Fahrbach, Department of Biology

Structural and structural studies of AKT oxidation in hormone signaling
Cristina Furdui, Internal Medicine, Gloria Muday, Biology: Leslie Poole, Biochemistry

January 2013

Immunolabeling synaptic proteins to track long-term effects of synaptic signaling in the brain
Susan Fahrbach, Biology

Imaging Protein Oxidation in Acid-secreting Renal Epithelial Cells
Glen S. Marrs, Biology, Snezana Petrovic, Physiology and Pharmacology; Cristina M. Furdui, Internal Medicine; and Leslie B. Poole, Biochemistry

Utilizing immunohistochemistry to characterize the neuronal pathways activated by nucleus accumbens serotonin receptor stimulation
Wayne Pratt, Psychology

June, 2012

Structure of Signaling RNAs in VSV
Rebecca Alexander, Chemistry and Doug Lyles, Biochemistry

Chemical Probes to study the Oxidized Thiol Proteome
Bruce King, Cristina Furdui, and Leslie Poole

Intramolecular Signaling of tRNA Folding
Sam Cho, Physics and Computer Science

February, 2012

Flavonoid modulation of insulin signaling in fat and muscle cells
Gloria Muday, Biology
Kim Nelson, Biochemistry

Mechanical signaling in tissue engineering: Effect of nanomechanical substrate properties on cell growth
Martin Guthold, Physics
Sang Jin Lee, Wake Forest Institute for Regenerative Medicine

Dissection of signaling networks maintaining metabolic homeostasis
Erik Johnson, Biology

May, 2011

Avian and Mammalian TRP channels as a Target of Insect Chemical Defenses
Primary Investigators:
Wayne L. Silver, Biology
Erik C. Johnson, Biology

Developing and Analyzing a Unified Model of Protein Interactions based on Replicate Data Sets with Independent Prior and Common Prior Distributions
David John, Computer Science
James Norris, Mathematics

Improvements of Computation Methods for Subnetwork Discovery in Biological Networks (Final report due)
William Turkett, Computer Science
Jacque Fetrow, Computer Science

Development and Application of Fluorescence Based Analyses of Protein-Lipid Targeting
Anita McCauley, Biology
Keith Bonin, Physics
David Horita, Biochemistry (WFU medical school)

Extramural Funding supporting center activity:

1) NSF Major Research Instrumentation (2007): Acquisition of the Confocal Microscope Center Participants: Gloria Muday, Susan Fahrbach, Erik Johnson, Martin Guthold, Anita McCauley

2) NSF Major Research Instrumentation (2010): Live Cell Incubation and Additional Lasers for the Confocal Microscope Center Participants: Gloria Muday, Erik Johnson, Bruce King, Leslie Poole, Karin Scarpinato, Anita McCauley

3) NSF, Chemistry Instrumentation (2009)Acquisition of a user-accessible Q-TOF mass spectrometer” PI Colyer, CoI Alexander, Major users include Poole and Muday