The student application requires that you choose two faculty that you would be interested in working with over the summer. Use the following descriptions of research projects to help in your decision.
Macon Campus - College of Liberal Arts
Linda Hensel - Department of Biology
Bacterial biofilms are produced through quorum sensing, creating a protective environment that will promote survival of pathogenic bacteria against traditional antibiotics. Inhibiting quorum sensing, and thus the production of biofilms, is a promising mechanism of defense against bacterial species. Bacteria-specific antimicrobials, compared to broad-spectrum antibiotics, are advantageous because they will not affect the growth of normal flora necessary for health of the patient. An optimal biofilm inhibitor would be specific for inhibiting biofilm formation signals, and therefore disabling quorum sensing for the pathogenic species. In addition, this non-traditional antibiotic is likely to decrease the prevalence of antimicrobial resistance. In three renditions of the BOMM CURE, over 300 novel lead compounds were synthesized by methods adapted from the D3 project (IUPUI) and tested against several different species of bacteria (B. subtilus, E. coli, S. aureus, P. aeruginosa, and Strepcococcus mutans). Modified crystal violet assays and ANOVA/paired Tukey tests, p<.05 were used to confirm biofilm inhibition and acceleration. Potential inhibitors were further tested with additional assays to determine bactericidal or bacteriostatic tendencies, and to find the minimum inhibitory concentration. A family of related tyrosine-based novel lead compounds demonstrate biofilm inhibition in S. aureus, phenylalanine-based novel lead compounds inhibit biofilm production in B. subtilus, and Tryptophan-based novel lead compounds in B. subtilis, S. aureus, S. mutans, as displayed by our database. Fifteen of these drugs were tested further. Results indicate that aromatic structures with a trans double bond with the addition of a carboxylic functional group are the most promising novel lead compounds for future research.
Amy Wiles - Department of Biology
The response of a cell to its environment is critical. How cells respond to nutrient stimuli is of particular importance, given that they require nutrients to grow and divide. Abnormal response to nutrients could result in excessive growth/cell proliferation or failure to grow/proliferate. In particular, we are using a systems biology approach to investigate the effect of sulfur and nitrogen on cell proliferation in the yeast Saccharomyces cerevisiae. To determine which genes are required for viability in limited sulfur or nitrogen conditions, we have screened a gene knockout library in S. cerevisiaeand have begun to validate it. Over the summer, a MUBS student will work on analyzing data from the current validations and continuing the validation. Gene/protein choice will be based primarily on if the novel protein has interactions with proteins involved in sulfur or nitrogen metabolism. During the summer, protein-protein interaction networks and pathways will be used as a framework for integrating the proteins of interest to determine how they relate.
Macon Campus - School of Engineering
Joanna Thomas - Department of Biomedical Engineering
Primary sclerosing cholangitis (PSC) is an autoimmune disorder of the liver, characterized by inflammation of intra- and extra-hepatic bile duct epithelium. Chronic inflammation of the cholangiocytes leads to the formation of strictures and likely cholestasis. Prolonged cholestasis causes inflammation to spread beyond the biliary tree resulting in portal hypertension and/or liver fibrosis. As the inflammatory response causes biliary strictures to worsen, standard intervention is placement of a stent via endoscopic retrograde cholangiopancreatogrophy (ERCP) to alleviate cholestasis and prevent bile acid toxicity.
Currently, there are no FDA-approved drug-eluting biliary stents. A drug-eluting biliary stent would offer targeted delivery of therapeutic compounds to cholangiocytes and nearby hepatic tissue. Two anti-fibrotic drugs, pirfenidone and nintedanib, are FDAapproved to treat idiopathic pulmonary fibrosis; these compounds could be effective in hepatic applications if hepatotoxicity can be avoided. A 3D-printed polymeric biliary stent, capable of sustained delivery of therapeutic compound(s) to the biliary stricture microenvironment would avoid the oral dosing concerns and could be an inexpensive and effective alternative to standard biliary stents for PSC patients.
We will be designing and fabricating 3D-printed biliary stents made of biocompatible polymers that elute pirfenidone, nintedanib, or both. We will evaluate the mechanical properties of the stents for equivalency to FDA-approved plastic stents. We will also confirm the biocompatibility of the stents and examine the antiinflammatory efficacy of the stents through cell growth and gene expression studies.
Sinjae Hyun - Department of Biomedical Engineering
Evaluation of the health and safety risks of products using particles including nano-sized particles is critical as there are ever increasing applications and sources as diverse as cleaning agents, food stuff, cosmetics, device fabrication, chemical processes, drug delivery, and textile weaving, to name a few. In addition, air pollutions from natural sources to tobacco smoke including e-cigarette smoke and unclean combustion exhausts contribute to the inhalation of particles as well. One of the most important factor affecting human health is the exposure to aerosol particles, especially fine (0.1-1 μm) and ultrafine (<0.1 μm) particles. Because of their larger diffusion coefficient, ultrafine particles have a higher probability than larger particles to penetrate and deposit deeper into the respiratory system.
Electronic cigarettes (e-cigarettes) are perceived as a healthier alternative to combustible tobacco products, with the potential to aid users in quitting or reducing cigarette consumption. From a technical perspective, the perception of the relative safety of e-cigarettes is based on their different mechanism of aerosol/vapor formation, compared with traditional combustible tobacco products. It is assumed that e-cigarettes do not generate many of the harmful and potentially harmful constituents (HPHCs), but published results show the presence of carbonyls and metals, in e-cigarette aerosol/vapor.
The chemical composition of e-cigarette emissions is an important, but not the only factor that contributes to the potential health impacts. Aerosol size is a critical parameter that defines the delivery of toxicants to the human respiratory system determining both delivery and deposition efficiency of each region of the respiratory tract.
Therefore, although the mass concentration of the nano-aerosol fraction could be significantly lower than the submicron particles, the toxicological effect of HPHCs and other chemicals attached to the nanoparticles could be high. High concentrations of metal nano-particles can also be generated using the glowing wire technique, which utilizes essentially the same resistively heated wire principle used in e-cigarettes. Although under normal operating conditions the presence of a wick impregnated with e-liquid provides a cooling effect, so-called “dry puffing” conditions, the e-cigarette may function as a glowing wire nanoparticle generator.
The main objective of this study was to measure the particle size distribution of aerosols generated by different types of e-cigarettes (“cigalikes” and tank-style), and to evaluate the characteristics of particle sizes under different thermal and humidity conditions.
Macon Campus - Mercer University School of Medicine
Ashley Horner - Department of Basic Sciences
It is well-known that an imbalance in activity between that patch and matrix systems of striatum underlies inflexible and repetitive behaviors, such as psychostimulant-induced stereotypy. Habitual drug abuse is also persistent and inflexible, raising the possibility that addiction is mediated by the patch-matrix system. Furthermore, previous work suggests that the patch system carries information relating to reward, which may also contribute to the eventual development of habitual drug use. We posit thathabit formation, as well as psychostimulant reward are due to predominant activation of the patch versus matrix system, which occurs due to the weakening of synaptic connections in matrix-based circuits.The goal of this project is to determine contribution of the patch-matrix system to habitual behaviors, as well as reward processes. Using chemogenetic techniques, we will examine whether an imbalance in patch-matrix activity contributes to METH-mediated reward and habit formation, using a METH self-administration paradigm. The proposed research is innovative because the patch-matrix system has not been examined as a possible pathway for reward and the development of habitual behaviors. Moreover, the specific contribution of patch-based circuits to drug reward has not been described, and therefore represents a novel pathway for drug-related reward processes. We expect the outcomes of these experiments will greatly add to our understanding of the neural systems that mediate habitual drug abuse.
Thomas Selby - Department of Biomdical Sciences
This project is focused on determining the role of non-enzymatic post-translational modifications (NEPTMs) on G-protein coupled receptor (GPCR) function. We will investigate these NEPTMs by determining the glycation positions of extracellular regions of two protease activated receptors (PAR1 and PAR2) and a free fatty acid receptor (FFAR4) known to be involved in energy metabolism and glucose regulation. We will investigate the propensity for modification of amino acids that are located on the extracellular surface of these receptors using glycating agents known to be produced metabolically or consumed in the diet. This will be accomplished using chemical assays, protein chromatography, fluorescence spectroscopy, and mass spectrometry to develop a propensity measurement to understand which amino acids are more rapidly modified. We will also monitor the kinetics of NEPTMs to determine how rapid these reactions occur in protease assays to validate our results. These kinetic measurements will provide an understanding of how extracellular regions (ECRs) of GPCRs are modified, as well as a time-scale and concentration determination of their biological relevance. As the locations of these modifications are revealed, we will use computational methods to determine the mechanistic changes that are likely to occur when the ECRs are modified and how these modifications alter receptor signaling by altering the conformational energy landscapes of the GPCRs during activation.
Atlanta Campus - Mercer College of Pharmacy
Kevin Murnane, Department of Pharmaceutical Sciences
The Murnane laboratory is studying potential new compounds that may reverse life-threatening overdose induced by opioids. These studies are particularly focused on fentanyl, as unlike overdose from other opioids, fentanyl-associated overdoses are resistant to naloxone therapy. Ongoing studies involve advanced drug-delivery systems, endogenous neuropeptide systems, and the endocannabinoid system. At the Mercer University College of Pharmacy in Atlanta, over the summer, the Mercer Undergraduate Biomedical Scholar will work on this project. He or she will receive training in behavioral pharmacology, neurophysiology, neuropharmacology, brain surgeries using computer-guided stereotaxic instruments, and nanotechnology-based drug delivery. The Mercer Undergraduate Biomedical Scholar will execute this project as a part of a larger team of faculty, PhD graduate student, and PharmD professional student colleagues.
Clint Canal - Department of Pharmaceutical Sciences
Radioligand binding is an exceptionally resourceful tool for basic and applied pharmacological research. Assays employing radioligand binding can: 1) Determine affinities of unknown compounds at receptor targets; 2) Determine receptor density (binding sites) in tissue; 3) Determine anatomical location of receptor targets; 4) Determine target engagement after systemic administration of a drug or medicine. Dr. Canal’s group recently discovered that certain psychostimulant drugs of abuse, called “cathinones,” which are similar to amphetamines, have off-target activity at G protein coupled receptors, including serotonin 5-HT2Aand muscarinic M1receptors. This activity might contribute to their toxicity and physiological effects. These observations also have major implications for further understanding the pharmacology of other drugs of abuse. Recently, for example, it was discovered that the potent opioid, fentanyl, has off-target activity at serotonin 5-HT1Aand 5-HT2Areceptors, which likely underlies serotonin toxicity associated with fentanyl use. Dr. Canal has a MUBS Summer Research Project open that uses tritium [3H] radioligands in order to continue investigating off-target activity of psychoactive drugs.