The range of research being conducted by ICAN members expanded with the awarding of funding from the Center's seed grant program. With the support of the College of Veterinary Medicine and the Vice President of Research and Economic Development, ICAN was able to provide $100,000 in funding for a variety of research projects in neurotoxicology. The six proposals funded during this first-round competition emphasized ICAN priorities for an innovative multi-disciplinary team research approach that is also competitive and well-positioned to attract additional external funding.
Research projects awarded under the first round of ICAN seed funding, with investigators and their departments, include:
"Ultra-sensitive Imaging of Nanomaterials, Pathogens, and Vesicular Transporters” by Dr. Ning Fang
Dr. Ning Fang, associate professor of chemistry at Iowa State University, received ICAN funding for his project “Ultra-sensitive Imaging of Nanomaterials, Pathogens, and Vesicular Transporters.”
Dr. Fang plans to work with other ICAN researchers in employing advanced imaging technologies in biological/medical research on neurotoxicology with the goal of observing activities of sub-diffraction-limit objects, such as nanomaterials, pathogens and vesicular transporters. He believes this will yield importance real-time information of various biological processes such as infection and signal transmission that are not yet understood.
“With the support of ICAN funding, I will be refining and sharing new technology in live cell imaging, Dr. Fang explained. Whereas most of today’s cellular research utilizes fixed cells and looks at the final effect of, for example, a neurotoxic chemical, ultra-sensitive imaging allows for a real-time examination of the process. I believe this dynamic visualization will have value to all molecular researchers at ISU.”
“Retinal Diagnostic Imagining in Rodent Models of Parkinson's Disease” by Dr. Matt Harper, Vet. Clinical Sciences; Dr. Arthi Kanthasamy, Biomed. Sciences; Dr. Sinisa Grozdanic, Vet. Clinical Sciences
Dr. Matthew Harper is a postdoctoral fellow in veterinary clinical sciences in the College of Veterinary Medicine. Along with other Vet Med co-investigators Drs. Arthi Kanthasamy and Sinisa Grozdanic, is investigating novel ways to longitudinally evaluate potential neuroprotective treatments for Parkinson’s disease in the same animal subject over a prolonged period of time. The plan is to then correlate these results with any anatomical preservation observed at the end of the study. The goal: a better understanding of how effective new drugs for Parkinson’s disease are and, from there, a smooth transition of the drugs in moving from benchtop to bedside.
Dr. Harper feels funding from ICAN is especially important. “These seed grants from ICAN are not only valuable for establishing new lines of research, but for bringing together investigators with different backgrounds and interests.
“In speaking with the Kanthasamy research group about our Parkinson’s project, we quickly realized we had other similar interests. We are currently working on a traumatic brain injury study in collaboration with a Center of Excellence headed by Dr. Randy Kardon (VA, Iowa City) and Sinisa Grozdanic (ISU, Veterinary Clinical Sciences), and hope to submit a grant this fall. These centers are very useful in bringing expertise together in an organized way, and having multiple resources available immediately.”
“It’s doubtful that the collaboration for this new project would not have been initiated without ICAN facilitating this funding.”
“Identification and Characterization of Novel Virulence Factors of Neonatal Meningitis Associated E.Coli Via Proteomic Analysis” by Drs. Lisa Nolan and Ganwu Li, Vet. Micro. & Preventative Med.
Their proposal is titled: “Identification and Characterization of Novel Virulence Factors of Neonatal meningitis Associated E. coli via Proteomic Analysis. “ But the question co-investigators Dr. Lisa Nolan and Dr. Ganwu Li, both microbiologists in the veterinary micro and preventative medicine in the College of Veterinary Medicine, are really hoping to answer is: What if E. coli-caused meningitis of babies could be traced back to contaminated food?
From this question came the hypothesis that 1) novel virulence genes responsible for hyper-virulence do exist and 2) genes that determine host specificity and/or tissue specificity also exist. The investigators will us proteomic analysis to identify virulent genes that may fall into these categories. Then the function of these genes and mechanisms will be clarified using molecular and cellular methods.
“We might be able to prevent this devastating disease by instituting certain food safety measures, Dr. Nolan explained. With funding from ICAN, we are testing this idea by determining if extra-intestinal pathogenic E. coli from food animals are host-specific. If they are not, they could be food-borne pathogens capable of causing meningitis in newborns. We believe this research will move us closer to answering this question.”
“Effects of Nanoparticles on Interface of Nervous and Immune Systems” by Drs. Dušan Palić and Eric Rowe, Biomed. Sciences
Zebrafish are the model for an ICAN project proposed by co-investigators Drs. Dušan Palić and Eric Rowe, both faculty members in the Department of Biological Sciences, College of Veterinary Medicine. They hope not only to address concerns about the introduction of various nanoparticles into aquatic environments from industry and household sources, but also to use the fish as models for examining the effects of nanomaterials on life processes at the molecular level.
Their proposal “Effects of Nanoparticles on the Interface of the Nervous and Immune Systems” proposes to use combination of microarray technology and transgenic zebrafish as high throughput systems to simultaneously identify changes in gene expression patterns and functions of t he neuroimmunological interface.
“Our hypothesis is that exposure to fulleren, titanium dioxide, and quantum dot nanoparticles will cause measurable changes in transcriptome responses and interfere with development of the nervous and immune systems in zebrafish,” Dr. Palić explained.
“Because there are currently no studies describing the effects of fullerene nanoparticles on the neuroimmunological interface, we feel we will harvest data of special significance. Even as invertebrates, zebrafish are remarkably well suited to serve a models for mechanistic studies of nanoparticle neuroimmunotoxicity.
ICAN investigators use zebrafish as bait for catching potential effects of nanotechnology on living organisms: Drs Dušan Palić and Eric Rowe investigate how increased bioavailability of nanoparticles in nature, but also in human and veterinary medicine, interact with immune and nervous systems.
“We are trying to determine if exposure to several classes of nanoparticles will cause changes in gene expression and development of the neuroimmunological interface” Dr. Palić explained. “Using transgenic zebrafish embryos alongside microarray technology provides us with powerful tool to rapidly screen for effects, as well as directly compare if, and to some extent how, changes in gene expression correlate with observed immune responses and neural development.”
Mr. Boris Jovanovic, Toxicology graduate student in Dr Palić’s laboratory, hopes that data stemming from this project will become part of his doctoral dissertation: “…because there are currently no studies describing the effects of nanoparticles on the neuroimmunological interface, we feel we will harvest data of special significance.”
Dr Rowe said that “We hope not only to address concerns about the introduction of various nanoparticles into aquatic environments from industry and household sources, but also to characterize a high throughput vertebrate model for examining the effects of nanomaterials on life processes at the molecular level. Zebrafish are increasingly utilized as model for human disease research, and we wanted to bring this novel technology to ISU and ICAN.”
“The C. elegans nAChR and parasitic disease; towards an effective model system for small molecule drug discovery” by Dr. Alan Robertson, Biomed. Sciences; Dr. Joanne Powell-Coffman, Genetics, Development and Cell Biology
Dr. Alan Robertson, research associate professor in Biomedical Sciences, expands his commitment to the study of the nematode C. elegans, with his project titled: The C. elegans nAChR and parasitic disease; towards an effective model system for small molecule drug discovery. Along with coinvestigators Joan Powell-Coffman (GDCB) and Adrian Wolstenholme (Bath, UK), Robertson is testing the hypothesis that C. elegans receptors are an adequate model for use in parasitic drug discovery. Although the organism does not belong to the parasitic group of nematodes, Robertson plans to transform his C.elegans subjects with parasite genes to mimic “parasitic-like” receptors. His hypothesis: that substitution in C. elegans subunit with a parasite ortholog will result in a “realistic” model that is functions well in a laboratory setting. Long term this will facilitate the development of small molecule screens for the discovery of new anti-nematodal compounds.
“We believe that our work in developing organisms for anti-nematodal research is of importance not only in animal health issues but in human populations as well where it’s estimated that more than 1 billion human infections occur annually.”
“Genomewide analysis of alternative splicing in oxidative stress” by Drs. Natalie Singh and Ravindra Singh, Biomed Sciences
Dr. Natalia Singh, adjunct assistant professor in ISU’s Department of Biomedical Sciences, received funding for her project titled: Genomewide analysis of alternative splicing in oxidative stress. In this work, she is examining the impact of oxidative stress from toxic compounds such as herbicides on “alternative splicing” -- a fundamental process for generating protein diversity in humans and animals.
Recent research has linked aberrations in alternative splicing to conditions of oxidative stress associated with neurodegenerative diseases such as Alzheimer’s (AD), Amyotrophic lateral sclerosis (ALS), Huntington’s, Multiple sclerosis and Parkinson’s (PD) diseases.
With her co-investigator Dr. Ravindra Singh, Dr. Singh has begun experiments using the latest microarray platform to capture global splicing changes in neuronal cells grown in vitro and treated with paraquat, one of the most widely used herbicides in the world and a known neurotoxin.
Dr. Singh is optimistic about her ICAN-funded research yielding a broad range of benefits. She explained, “We expect our results to shed light on one of the most fundamental causes of oxidative stress and, when shared, to stimulate collaborations among other ISU faculty studying oxidative stress-associated diseases in both humans and animals.”