Dr. Robbin Eppinga, Assistant Professor of Biology
Characterizing Proteases Involved in Cancer Invasion and Metastasis
Cancer is the second leading cause of death in United States (CDC; http://www.cdc.gov/nchs/fastats/lcod.htm) and a major disease globally. If detected before cells in the primary tumor metastasize (spread to other organs), the disease can be ‘cured’ by surgically removing the tumor. For most types of cancer, the metastatic recurrence, not the primary tumor, ultimately proves to be fatal (Bird et al., 2006). Therefore it is critical that we better understanding the mechanisms of cancer metastasis and identify therapeutic targets.
We culture cancer cell lines and an immortalized non-cancer cell line, and use standard cell and molecular biology techniques to ask a host of questions regarding cancer metastasis. These include:
- Which proteases are used to degrade the extracellular matrix during cancer metastasis?
- How is protease production/secretion regulated during metastasis?
- Do non-tumor cells that are normally involved in extracellular matrix remodeling assist the escape of cancer cells from the primary tumor? How is this accomplished?
We have recently used pharmacological inhibitors of the metalloproteinase (MMP) in an invasion assay to discover that this protein family is responsible for degrading the extracellular matrix by one of our cellular model systems. Students are currently isolating mRNA and protein from this cell line during invasive and non-invasive conditions, and performing RT-PCR, Western blot analysis, and Gel Zymography in order to determine which of the MMPs is responsible for degrading the matrix, and how this MMP is regulated during tumor cell invasion.
Student interns: Kim Buyert, Sam De Nooy (2013)
Identifying Myosin V-Interacting Proteins Involved in Intracellular Transport
The motor protein myosin V mediates trafficking of vesicles, mRNAs and other cargoes within cells to assist in cellular secretion, melanin trafficking, proper neuronal function and cell movement (McCaffrey & Lindsay, 2002; Bond et. al., 2011; Eppinga et al., 2008). One end of the myosin V attaches to and moves along the actin cytoskeleton while the other end has the curious ability to bind to a host of different cargoes. Several cargoes have been identified for Myosin Va including RNA, melanin, and neurotransmitter vesicles, but the adapter proteins that link the myosin Va to its cargoes are largely unknown.
We have performed a yeast-two-hybrid screen to identify adapter proteins that interact with myosin Va. Initial characterization of the resulting clones has been performed by students in the molecular biology class (Read the Story here). Some of these students presented their findings at the University of Iowa (Read Story Here). Currently, we are characterizing a subset of the clones that have been pulled out of the screen. Students working on this project have been isolating and sequencing plasmid DNA and analyzing these sequences. Several potential myosin-interacting clones have been identified. Future work includes expressing these genes in tissue culture cells to validate the interactions and performing functional studies to assess the role of the interactions within cells.
Dr. Tony Jelsma, Professor of Biology
Mechanism of Action of the Cux1 gene in Developmental Processes
My research interest is in the mechanism of gene regulation by the transcription factor Cux1. Cux1 is present in a variety of developing tissues, where it is generally found in dividing cells. We studied its expression in the testes, where it is expressed in Sertoli cells and spermatids, neither of which is a dividing cell population. Although its biological functions in the testes are unknown, our further immunohistochemical studies suggest that Cux1 in Sertoli cells regulates the division and survival of spermatogonia.
We are also beginning a project to look at the role of Cux1 in brain development. Cux1 is present in a specific layers of the cerebral cortex, where it appears to regulate neurite branching. In addition, Cux1 appears to be linked to depression. We have begun a research project using the yeast two-hybrid system to identify proteins that partner with Cux1 in its regulation of gene expression, to gain further insight into its function in these other tissues.
Student interns: Brandon Wubben (2013), Sam De Nooy (2012), Erica Lieuwen (2011), Will McClain (2011), Deb Jude (2010), Melissa Kroll (2008)
Dr. James Mahaffy, Professor of Biology
Investigating the range of the Prairie rattler (Crotalus viridis) in Northwest Iowa
I have been following up on reports of rattlesnakes being found in shortgrass relict prairie in counties both north and south of the known locality near Westfield in Plymouth County, Iowa. Since the Westfield location is the easternmost extent of the known range and the only place the snake has been proven to exist in Iowa (where it is endangered), these reports would be of interest to the state and the herpetological community if they prove to be true. In the food plains of the Little Sioux River, I have found that there were rattlesnakes in wet meadows. The habitat of these is more suggestive of the massasauga than the prairie rattler. Unfortunately, habitat changes due to agriculture have probably resulted in this population being extirpated. An offshoot of this study has uncovered historic extensions of massasauga or probably massasauga in western Iowa (Crawford and other counties), northeastern Iowa (Mitchell County) and adjacent Mower County in southeast Minnesota and more recent evidence for rattlesnakes across southern Minnesota in the Mankato area.
Student interns: Katie Tazelaar (2013), Monica McConnel (2012)
Dr. Jeff Ploegstra, Assistant Professor of Biology
DNA fingerprinting and Endangered Ecosystems
It is a little known fact that the tallgrass prairie is one of the most endangered ecosystems in North America (Fletcher and Koford, 2002; Johnson, 2003). Before European settlement, 79% of Iowa’s landscape was tallgrass prairie; now, less than 0.1% of native prairie remains. Plants native to the tallgrass prairie now exist in small fragment populations and risk extinction from habitat loss and isolation. Reduced population sizes can lead to a loss of gene flow and genetic diversity within populations that may reduce the potential for adaptation under changing environmental conditions.
We use DNA fingerprinting to examine the genetic diversity, population structure and gene flow of butterfly milkweed (Asclepias tuberosa) a wildflower common to prairie remnants. We collect DNA samples from remnants and examine the differences among the samples at specific locations in the genome. We compare the differences within and between populations to answer questions like:
- How genetically diverse is this population?
- How different is a population from a population at another location?
- Are there greater differences depending on geographic distance and connectivity?
The answers to these questions can help land managers make decisions about restoration efforts.
Student interns: Brittany De Ruyter (2009), Zack Petersen (2011), Michelle Alkema (2011, 2012), Kayla Graves (2012), Geno Maule (2013), Rebekah Benson (2013)
Perennial plants, growing in mixtures, make up most of the world’s natural terrestrial biomes. In contrast, monocultures of annual crops are sown on more than two-thirds of global cropland. Grain and oilseed crops are the foundation of the human diet, but to date there are no perennial species that produce adequate grain harvests. Yet perennial plant communities store more carbon, maintain better soil and water quality, and manage nutrients more conservatively than do annual plant communities, and they have greater biomass and resource management capacity (Cox et al, 2006).
We have been working to support projects initiated by the Land Institute in Saline Kansas to develop Intermediate Wheat Grass (IWG) as a viable perennial crop. We have specifically been comparing the interactions between the genetics of 70 varieties of IWG and our local environment. We have also examined the influence of mother plant characteristics on seed development, germination, and early growth. In the near future, we plan to examine the genetics of host-pathogen interactions using RNA-Seq technology.
Student interns: Zack Petersen (2011), Michelle Alkema (2012), Kayla Graves (2012), Jon Luetchens (2013), Geno Maule (2013), Rebekah Benson (2013)
Grassroots Plant ID App: Next Generation Environmental Education
Our global society is increasingly urban, increasingly mobile, and individuals living in rural settings are spending less time in nature. This is of great concern to environmentalists and should be of great concern to Christians broadly. It is difficult to motivate individuals to care for what they do not know, understand or interact with. Today’s society is also far more technologically savvy.
In order to help individuals become more familiar with the local environment, we are working to construct a plant identification app for tall-grass prairie plants. Though there are several Plant identification Apps available, they suffer from several critical deficiencies:
- They tend to be too broad geographically- so you get false positives- I generally shouldn’t pull up a plant from the west face of the Sierra Nevada’s when I am in the Great Plains.
- The pictures are generally terrible for use in differentiating plants.
- The terminology and interface is not generally user friendly.
- They don’t have “buildable” databases- you can’t add to the plants in the database or indicate easily where a user may have identified a plant- or even that they have seen a particular plant.
- They are often expensive. We plan to offer this app for free.
- They tend to ignore “weeds” and exotic species.
- They usually don’t include grasses.
The proposed app would allow individuals to input easy-to-understand characteristics and receive back a list of matching plants with diagnostic photos for each. A conceptual framework for the app and a database of 120 of the most common prairie plants have already been developed. Additionally, the platform will be designed to be updated and populated easily by experts. This would mean that the platform could be used by individuals in other geographical locations to populate their own database for local use.
Student interns: Geno Maule (2013), Rebekah Benson (2013), Steve Spurgeon (2013)
Dr. Robert De Haan, Professor of Environmental Studies and Biology
Soil Nitrate Levels and Land Management Practices
The research I am engaged in currently is designed to examine the impact of farming practices on the movement of nitrate nitrogen through the soil profile. The city of Sioux Center, like many towns in the Midwest, obtains much of its water from shallow wells less than 40 feet deep. Nitrate levels in these wells are clearly affected by land management in the watershed. A better understanding of nitrate dynamics may help us reduce the likelihood of nitrate movement to groundwater, while still maintaining a productive agricultural system.
Dr. Nathan Tintle, Associate Professor of Statistics
Statistical Analysis of Genomes to Study Disease and Metabolic Pathways
Technological breakthroughs within the last few years have ushered in a new era of big data in genetics. In large part, my research is involved with designing statistical, mathematical and computational methods which use our increasing knowledge of the complexity of bacterial, plant, animal and human genomes to provide better interpretation of DNA and RNA sequencing data. In particular, we are currently exploring (a) methods to provide better understanding of the impact of rare genetic variations in the etiology of complex human diseases and (b) characterization and utilization of bacterial metabolism and genetic regulation on a massive (all sequenced bacterial genomes) scale. I actively collaborate with leading biologists, chemists, computer scientists, mathematicians and other statisticians at Dordt, around the country and around the world on a series of methodological and applied projects in these areas, since it is only through these interdisciplinary collaborative research approaches that meaningful research in these areas can be done. In addition to a primary research agenda in statistical genetics, I also continue to work in public health and epidemiology, as well as in measurement and assessment in statistics education. You can read more specifics about our current academic year and summer research projects, results and published papers by visiting: http://www.dordt.edu/statgen.
Student interns: Jaron Arbet (2013), Alejandra Benitez (2013), Jake Clark (2013), Kaitlyn Cook (2013), Derek DeVries (2013), Casey Fu (2013), Kelsey Grinde (2013), Jordan Huisman (2013), Brittany Kooiker (2013), Michael O'Connell (2013), Ben Olthoff (2013), Lauren Opp (2013), Ally Rogers (2013), Jason Westra (2013)
Dr. Darren Stoub, Associate Professor of Chemistry
Investigating Mechanisms of Action of Integrins
Integrins are cell surface proteins involved in cellular communication and demonstrate complex signaling pathways. Using medicinal chemistry, structural biochemistry and molecular biology, we are investigating how integrins are activated to carry out their function. By investigating these pathways, we are seeking to discover and understand drugs that treat integrin-associated diseases, such as inflammation and cancer metastasis.
Student interns: Caleb Boehler (2013), Christy Sikkema (2012, 2013), Paige Roos (2012)
Engineering Bioluminescent Proteins
Luciferases are proteins that glow in response to chemical signals. We are investigating and modifying the structure of Gaussia Luciferase, the smallest luminescent protein, in order to diversify and expand its luminescent properties. We hope to produce a kit that can be used to identify the presence of biological agents.
Student interns: Crystal Elenbaas (2013), Deborah Tyokighir (2012)
Dr. Carl Fictorie, Professor of Chemistry
Developing New Catalysts for Biodiesel Production
Biodiesel is an alternative type of diesel fuel obtained from renewable resources. Vegetable oils can be used directly in diesel engines but raw oils cause a number of engine problems, many relating to the high viscosity and low volatility of the oils. To address this problem, the oils are treated with an alcohol with a catalyst and thereby undergo transesterification. This process produces fatty acid methyl esters, which have fuel properties similar to those of petroleum-based diesel fuel. In the Midwest United States, soybean oil and corn-based ethanol are widely available so it is logical to develop fully renewable biodiesel, using these regionally produced materials. In our work we are designing catalysts for the transesterification of soybean oil and ethanol. We have found that corn stover, the stalks and leaves of corn, can be pyrolyzed to form charcoal, which when sulfonated with sulfuric acid, forms a solid acid catalyst with potential for use in biodiesel synthesis.
Student interns: Sophie Jin (2013), Travis Kooima (2013)
Dr. Channon Visscher, Assistant Professor of Chemistry and Planetary Sciences
Modeling physical and chemical processes in planetary and astrophysical environments
Ongoing research projects are divided into two main categories:
Chemistry and clouds in substellar atmospheres
The goal of this work is to better understand the underlying chemistry responsible for the observed properties of planetary atmospheres. I am involved in a comprehensive study of chemistry in the atmospheres giant planets (Jupiter, Saturn, Uranus, Neptune), exoplanets (planets orbiting stars other than the Sun), and brown dwarfs (“failed stars” with insufficient mass to sustain hydrogen fusion). This work includes modeling reaction chemistry and cloud formation – including exotic clouds consisting of rocky material or metals – in planetary atmospheres and exploring potential effects on observational properties.
Chemistry and composition of the forming Moon
The goal of this work is to provide clues about the formation and evolution of planetary systems, specifically exploring the chemistry of the forming Moon. In the prevailing hypothesis for lunar origin, the Moon formed from an Earth-orbiting disk of rocky debris that was produced by the collision of a large planet with the Earth early in its history. Understanding the physical and chemical processes that may have affected this high-temperature (molten rock + vapor) debris disk is important for understanding the observed chemical abundance patterns in lunar samples (provided by meteorites and the Apollo missions), and may provide further clues about the origin of the Moon.
Dr. Kayt Frisch, Assistant Professor of Engineering
Quantifying Breathing Mechanics Using Lower Radiation Doses
Many lung diseases alter the ability of the lungs to perform gas exchange (i.e. breathing) by changing the tissue biomechanical properties. Lung mechanics are a predictor of lung function and can be quantified non-invasively by performing image registration of CT scans at different lung volumes, but excessive exposure to the x-rays used to create images is harmful. In an effort to lower the x-ray radiation dose from a single scan, we are comparing the mechanical descriptors for swine lungs imaged with varying levels of radiation.
Student interns: Andrew De Haan (2013)
The Effects of Impact Mechanics and Chest Protectors on Commotio Cordis
Commotio cordis (CC) is a rare phenomenon in which the heart stops beating after a blunt object strikes the chest directly over the heart during a short “vulnerable window” of a heartbeat. Commercially available chest protectors do not prevent CC, since 25% of fatalities are wearing chest protectors at the time of impact. We are using high speed video and mechanical compression testing to investigate how the mechanical properties of the impact objects and chest protectors affect the occurrence of CC in a swine model. The long-term goal of this project is to provide information to design better chest protectors to reduce the incidence of CC.
Student summer interns: Rebecca Megchelsen (2013)