An overview of the research performed by CSAM’s Science Honors Innovation Program (SHIP) Scholars.
SHIP is made possible by the generous support of the Merck and Roche Foundations.
Identification of allosteric residues involved in inhibitor binding specificity in the dihydrofolate reductase family
The importance of Dihydrofolate reductase (DHFR) arises from its function in DNA biosynthesis and cell replication. Inhibition of DHFR can lead to inhibition of cell growth, which has made the enzyme a pharmaceutically relevant drug-target. Understanding factors that influence DHFR homolog inhibitor specificity is critical for the design of compounds that selectively target DHFRs from pathogenic organisms over the human homolog. In an earlier article that used a quantitative analysis to predict residues away from the active site that play a key role in ligand specificity in the DHFR enzyme family.
My research focus is to experimentally validate this newly developed, predictive method. DHFR is important to cell growth and the method is being used to indentify allosteric residues in the family that influence ligand specificity. If the method is validated, it will be used to identify existing DHFR inhibitors to selectively target specific DHFRs from infectious organisms over the human homolog. As part of this project, I performed site-directed mutagenesis and purified DHFR mutants. Currently, I am working to determining the binding affinity of the created mutants vs. the wild-type enzyme on three different ligands, to decipher the ligand specificity of various mutants. We have already found specific mutations away from the active site that drastically alter the ligand/drug specificity of our test DHFR from B. stearothermophilus. Ultimately, we hope this novel approach can be automated. If automated, this approach has the potential to drastically reduce the drug development costs of many diseases of the developing world that have been relegated to neglected status.
SHIP Researcher: Michael Little
CSAM Mentor: Prof. Nina Goodey, Dept. of Chemistry
SHIP Researcher: Nanci Fioravanti
CSAM Mentors: Prof. Joseph DiGianni and Dr. Rolf Sternberg, Dept. of Earth and Environmental Sciences
SHIP Researcher: Katrina Bandeli;
CSAM Mentor: Prof. Aihua Li, Dept. of Mathematical Sciences
Ferrofluids are colloidal fluids, which contain nanoscale ferromagnetic particles that are evenly dispersed throughout a carrier fluid. Due to their small size, the magnetization of the particles averages out to zero in the absence of an external magnetic field. This phenomenon is known as superparamagnetism. The surfactant coating of the superparamagnetic nanoparticles enable them to form stable monolayers at the air/water interface. These monolayers can be
considered quasi-two-dimensional systems where the particles are confined to a surface while their magnetizations are free to rotate in all directions. Confining the nanoparticles to a surface allows observation of structure formation that is difficult to see in a bulk, opaque ferrofluid. We study pressure-area isotherms of such systems under lateral compression in a Langmuir trough. Once the monolayer is formed, it can be transferred to a substrate through either the Langmuir-Blodgett or the Langmuir-Schaefer technique. Once transferred, the monolayer can be analyzed using Atomic Force Microscopy as well as Scanning Electron Microscopy. In lieu of a substrate transfer, Brewster Angle Microscopy can be used to observe the monolayer on site. Each method reveals structure formations that would otherwise be difficult to observe.
SHIP Researcher: Goran Dojcinoski
CSAM Mentor: Prof. Patrick Truitt, Dept. of Mathematical Sciences
The biotic integrity of many aquatic ecosystems has significantly declined due anthropogenic effects on these environments, such as land use and land cover.
This study evaluated land use effects on periphyton growth at three different watersheds (urban, agricultural and forested) in Northern NJ. Periphyton biomass, growth rate and carrying capacity were assessed at both headwater and downstream sites of these three watersheds. Periphyton was sampled using artificial substrates during the summer and fall of 2012. The dry biomass at each site was evaluated at a weekly interval. The results indicate that the agricultural watershed provided the best growing conditions for periphyton. The dry biomass of periphyton at the downstream of the agricultural watershed was the highest 76.167mg, greater than urban 13.050mg and forested 12.300mg downstream biomass. Additionally, the highest periphyton growth rate was found at the downstream of the agricultural watershed 4.9476mg/d, greater than urban 2.900mg/d, and forested 1.236mg/d downstream growth rates. After seven weeks of exposure, periphyton growth leveled off in the agricultural watershed, reaching carrying capacities of approximately 47.368mg/m2 at the downstreamand 42.105 mg/m2 at the upstream sites.
SHIP Researcher: Merari Mejia
CSAM Mentor: Prof. Meiyin Wu, Dept. of Biology and Molecular Biology / Passaic River Institute
After the 9-11 World Trade Center tragedy, several health issues became common to those first rescuers and residents nearby, who had inhaled the resulting WTC particulate matter. Despite preliminary studies on the composition of this WTC dust, there are not many physiological studies that clearly state whether there are any detrimental effects that arise due to such particles. We seek to determine whether WTC dust may have more subtle effects by performing cell health analyses on human lung fibroblasts, which are pulmonary connective tissue cells. The study of the effects of Cadmium sulfate, and Lead acetate, Zinc sulfate, and WTC dust is done on human lung fibroblasts. It is hypothesized that Cadmium sulfate, Lead acetate, and WTC dust are toxic agents to mammalian cells. On the others hand, observations
are carried to analyze possible beneficial effects of Zinc sulfate treatment in vitro using techniques such as cell membrane assays.
SHIP Researcher: Patricia Rivera
CSAM Mentor: Prof. AnnMarie DiLorenzo, Dept. of Biology and Molecular Biology
To accurately assess flood hazards it is best to have the longest possible record of floods. However, a maximum of 100 years of historic flood events are recorded in New Jersey and most other states, and these are rare. Calculations on big flooding events—such as the 300, 500, or 1000 year flood— based on these written records will be more precise than accurate. Lakes sediments the history of big flooding events. The purpose of this research project is to create a paleoflood history of New Jersey for about the last 2000 years by analyzing lake sediment. The sediment samples went through a Loss on Ignition (LOI) analysis in order to identify potential paleofloods. As an alternative to radiocarbon dating, the samples went through a secular variability analysis in which I will reference my paleoinclinations to existing paleoinclination data in order to provide dates to the paleofloods. By obtaining this paleoflood history of New Jersey, we may extend the current records we have on big flooding events and contribute to the better understanding of flooding events that have and will happen.
SHIP Researcher: Diana Flores
CSAM Mentor: Prof. Josh Galster, Dept. of Earth and Environmental Studies
Working with the data that has been extracted from UniProt and the BindingDB, I've researched standard query optimization techniques and applied a modification of these techniques to help with the database’s issues. I've been exploring database and software issues with regards to a phylogenetics-based protein-ligand data repository. I will continue to increase the speeds at which the DrugTree’s database will read through the individual items of each table. Currently, the repository has a beta tool in place. This layer interacts with the Web Server and the Database Repository and Tree Generator levels. User’s personal queries are now easier to break down and filter against the databases. Once the final query plan is selected I will implement my research into more portable devices that will allow scientist to conduct their research on the move.
SHIP Researcher: Marvin Lapeine
CSAM Mentors: Prof. Katherine Herbert and Prof. Emily Hill, Dept. of Computer Science
The Kittatinny Ridge is the first prominent ridge of the Appalachian Mountains and is visible from New York to Alabama. Its composition is a weather-resistant sandstone conglomerate of Silurian age. Its consistent composition allows us to investigate variability in long term erosion rates along the ridge. Our project uses Geographical Information Systems (GIS) to delineate rivers and determine their longitudinal profiles and valley hypsometries. We see variations between the northern and southern portions of the ridge. The northern part of the ridge, such as the rivers in New Jersey, have a more convex profile shape whereas the southern part of the ridge, such as the rivers in Tennessee, have a more concave profile shape. This shows variations in long-term erosion of different parts of the ridge. These variations can be a result of different influences such as local climate, glacial history and local structure. In order to ground truth the data from GIS we conducted a survey of random streams in the field using a TopCon Total Station.
SHIP Researcher: David Sharpe
CSAM Mentor: Prof. Josh Galster, Dept. of Earth and Environmental Sciences
There are patterns that appear in nature very regularly, such as spirals and waves. We make note of these types of patterns and ask why nature seems to prefer these patterns over others. By using graph-theoretical methods, we construct distributions and analyze the configuration space of a particle on a grid of varying characteristics. With relatively few constraints, we find many possible paths for the particle to take, but very few of them resemble organized structures; in some configurations, only one or two configurations have these characteristics. The physics of the problem allude to some deeper reason for these patterns emerging so frequently in nature; we intend to continue to explore further aspects of this problem.
SHIP Researcher: Wayne Ernst
CSAM Mentors: Prof. Ashwin Vaidya & Prof. Jon Cutler
The need to extract natural resources to meet energy demands in the United States persists. This project reviewed the geological history of the Marcellus Shale of the Appalachian Basin in the North Eastern US and to hypothesize the significance and lifespan of the resource. Data was collected from the US Energy Information Agency and Pennsylvania Department of Environmental Protection regarding number of wells, well production, and locations. The main focus is on horizontal wells and classifying the wells with respect to production. A simple mathematical model is then used to evaluate how long the resource will last with certain assumptions taken regarding energy demand and max/min number of wells. We found that the shale is comprised of Devonian age hydrocarbons derived from organic rich deposits in an epieric sea. It contains approximately 14.2 Trillion cubic meters (Tcm) of recoverable natural gas. My preliminary estimate suggests if present rates continue than the resource could last for approximately 80 years. Concern of climate change, pollution, and other associated effects due to the primary fossil fuel exploitation are significant and a transition to cleaner fuels such as natural gas may be attractive.
SHIP Researcher: Kenneth Svolto
CSAM Mentor: Prof. M. Kruge
After 9-11, World Trade Center dust can severely damage human lung cells and cause pulmonary diseases. We are interested in observing the effects of WTC dust on human pulmonary fibroblast, specifically the apoptosis and the proliferation rate change of the cells by the dust. We are currently quantifying the rate of apoptosis, proliferation and cytotoxicity of human pulmonary fibroblast after altering pH of the WTC dust by adding biological buffers. We have found that biological buffers, such as bicarbonate ions, lowered the rate of cell death and increased the rate of cell growth. By adjusting pH of hazardous particulate matters with biological buffers, we hope to prevent the rapid cell death and reduce cellular damages caused by them.
SHIP Researcher: Sung Choi
CSAM Mentor: Prof. A.-M. DiLorenzo
Increasing energy demands and risings concerns over pollution have created a outcry for innovative sources of clean renewable energy. Using a simple mathematical model, we are analyzing the potential energy available in the motion of a cylindrical particle oscillating in a fluid substance. The potential energy captured in this motion is then converted into electrical units and compared to practical application in common households, like the ability to power a light bulb. We have placed a cylindrical particle in a moving fluid and allowed it one degree of motion along an axis that is perpendicular to the flow. By analyzing its oscillatory motion and comparing the power generated to a series of Reynolds Numbers, we can formulate a relationship between the electrical output and an increase in both flow velocity and particle dimensions. We found that a small electric generator, placed under certain conditions can utilize fluid dynamic phenomena to provide a small but substantial contribution to the net electrical demand of a system. As our societies energy demands increase, the ability to generate electricity from multiple localized sources can provide both a clean and valuable solution.
SHIP Researcher: Michael Cohrs
CSAM Mentor: Prof. A. Vaidya
Electronic health record systems which have been developed by different vendors are widely used today, so it is necessary for a standard that allows for the easy communication between these systems to exist. We are taking a look at the Medical Markup Language (MML) initially developed in Japan in 1995. MML follows the syntax of the Extensible Markup Language (XML) with domain specific tags and attributes relating to the medical profession. In our work we investigate the deployment of MML to store and analyze patient data worldwide in conjunction with cloud services. The wide adoption of digital medical records will streamline how patient information is stored, viewed, and transferred therefore saving energy, paper, and precious time all while hopefully increasing accuracy of diagnoses.
SHIP Researcher: Jonathan Tancer
CSAM Mentor: Prof. A. Varde
Licorice root Glycyrrhiza sp., is cultivated mainly in parts of Asia and Europe. Licorice root has a wide variety of medicinal applications including the treatment of stomach ulcers and bronchitis. We are investigating the inhibitory effects of glycyrrhizin on the replication and infection of Sindbis virus (SINV) in cultured Vero cells. Plaque, attachment and penetration assays are being used to quantify the viral particles released from infected cells following treatment with glycyrrhizin. The concentration of viral RNA produced in virus infected cells was measured and compared to glycyrrhizin treated and non-treated Vero cells to determine any inhibitory effect on viral RNA replication. We have found that glycyrrhizin can inhibit the infection of SINV in cultured Vero cells but appears to have no discernible effect on SINV nucleic acid replication. Glycyrrhizin inhibits SINV, the causative agent of Sindbis fever in humans (a disease endemic to parts of Europe, Asia, and Australia); our findings implicate the use of glycyrrhizin as a specific treatment for Sindbis fever (as opposed to the current method of treating the symptoms of the fever separately with different medications).
SHIP Researcher: Yvonne Okereke
CSAM Mentor: Prof. S. Adams
Anthropogenic nutrient addition has caused algal blooms in aquatic ecosystems around the globe. This study aimed to survey bloom-forming Cyanobacteria and algae in 13 New Jersey lakes. Water samples were collected from three locations at each lake in summer 2011. Approximately 500 mL of collected water sample from each sampling location were filtered to examine population densities and abundance. Specimens on filtered paper were identified by morphological characteristics under microscope observation. Lake Saginaw was found to have the highest populations at 6,374 cells/L and Tauton Lake was recorded the lowest at 13 cells/L. The species richness was found to be the highest at Lower Lake (25), and the lowest at Mt. Misery Lake (1). Shannon-Weaver Biodiversity Index numbers was calculated to assess the biodiversities in study sites. Results of the indexes ranged from 1.64 to 0 with the highest at Echo Lake and the lowest at Mt. Misery Lake. Genus Synneccocus was found to be the most abundant and was the dominant species in 11 out of the 13 lakes.
SHIP Researcher: Stephanie Lear
CSAM Mentor: Prof. M. Wu
The dynamics of the East Antarctic Ice Sheet (EAIS) during the Pliocene Epoch is of importance due to its characteristically warm climates and similar geological configuration of continents to that of present day. Located on the Wilkes Land Margin continental shelf, IODPExpedition 318 Site U1358B is positioned offshore a subglacial basin making it an ideal location to study EAIS dynamics due to the sensitivity of marine-based ice to warmer ocean currents and surface temperatures. An analysis of composition and provenance of diamicts (sediment of varying size) using heavy mineral, bulk geochemical, and particle size distribution was performed to further understand ice sheet behavior. The East Antarctic ice sheet behavior in the Pliocene warm period will be investigated through the analysis of sediment distribution using a Malvern Mastersizer 2000, heavy mineral assemblage with SEM-EDS, geochemical analysis using ICP-OES, and down core provenance investigation from the early-Pliocene to Pleistocene. Current interpretation suggests a grounded ice sheet with an un-weathered Wilkes Land Margin signature composed of low-grade metamorphic basement rocks with felsic properties unaffected by chemical weathering during the Pliocene. This investigation will contribute to the knowledge of EAIS behavior in past warm conditions in order to further understand its behavior in future warm climate conditions.
SHIP Researcher: Nadine Orejola
CSAM Mentor: S. Passchier
Overload in sediment can cause impairment in rivers, in this case a river that leads into a reservoir which provides drinking water to much of northern New Jersey. Using radionuclides Pb210 and Cs137 to source where fine grained sediment in the Rockaway river is being delivered from. Using the radionuclides helps source whether the sediment in the Rockaway River is being delivered from channel or surface erosion. Radionuclide noise is detected in a Genie Gamma Ray Detector. Currently preliminary data shows low levels of Pb210 which originates in the channels of the river. The Rockaway River leads into the Boonton reservoir which provides drinking water to much of northern New Jersey.
SHIP Researcher: Anita Trajkovska
CSAM Mentor: Prof. J. Galster
RET is a ret-proto-oncogene that codes for a receptor tryrosine kinase which is required for kidney formation and development of the enteric nervous system. Mutations in this gene can result in several neurodegenerative diseases. The RET gene has three distinct isoforms or variations. The isoforms are RET 9, 43, and 51. The two most common and well studied isoforms are RET 9 and 51 which suggests differences in signaling and functions. The purpose of my research project is to study the regulations of the RET isoform expressions using Reverse transcription and quantitative polymerase chain reaction to allow for the analysis of RET9 and RET51. After designing primers specific to my two RET isoforms, RET 9 and RET51, I ran an RT-PCR reaction, followed by a PCR reaction to observe expression levels. The expression levels of these two isoforms are then compared to a Universal 18S RNA primer which is the internal control. Once the RT-PCR conditions are optimized, the transcriptional level of the two RET isoforms are hypothesized to be affected by the presence of its ligand, GDNF (glial cell line-derived neurotrophic factor). I expect to see and measure changes in the expressions of RET9 and RET51 with respect to GDNF treated and untreated cells. So, far the results I have collected are inconclusive. Once we are able to observe the transcriptional expression of these genes, we may then be able to understand the signaling mechanism behind the gene and what triggers it to malfunction and cause diseases. By understanding the mechanisms, we may be able to find a cure or efficient treatments for the diseases caused by mutations.
SHIP Researcher: Binta Jalloh
CSAM Mentor: Prof. Q. Vega
Some species are characterized by sexually dimorphic male coloration and courtship behavior that evolved through intersexual selection, but this is not the case for mosquitofish. We are aiming to explain if coloration in male mosquitofish was lost due to lack of female preference or because males somehow avoided evolving it under intersexual selection. We are trying to look at why these mosquitofish (Gambusia) do not display similar courtship behavior to their close relative, the guppy. Our study is designed to test our hypothesis that male mosquitofish avoided evolving color due to the cost (i.e. predation) it bears. Additionally, we hypothesize that the innate female preference for coloration still exists but is no longer observed due to the lack of colored males. We have found that female Gambusia are not only attracted to color, but furthermore are only attracted to color when it is on a male. Our results suggest that male animals, not only our studies Gambusia, within a specific species where male ornamentation is exhibited as a mating strategy often do so at a high cost.
SHIP Researcher: Ariel Casner
CSAM Mentor: Prof. S. Kight