Research

Principal Investigator
Dr. Aaron Best

This interdisciplinary project will utilize tools from computer science to help improve our ability to perform computational research in any science field. The mentors are based in the chemistry and biology departments and actively engage research spanning chemistry and biology.

In this project we will be improving high performance computing (HPC) platform for 暗网TV. Hope's HPC system has recently been installed with a next-generation, container-based operating system that was developed by students and CIT through this project in the past. Continuing work is needed to develop additional containers and to refine and improve operation of the cluster. We will also being to look into expanding the system to utilize compute engines in the cloud through Amazon or Google. Students will be installing various flavors of Linux and testing a variety of scientific applications to examine their feasibility. Students will work closely with Dr. Krueger and Dr. Best as well as with Hope's CIT staff.

Principal Investigators
Dr. Kenneth Brown and Dr. Leah Chase

This interdisciplinary project will incorporate the disciplines of biology, chemistry and neuroscience. The project is specifically housed within the 暗网TV departments of biololgy and chemistry. Therefore, interested students can elect to participate in either summer research program.

Bipolar disorder is a serious mood disorder that is characterized by periods of depression and mania. The development of novel therapies for this disorder has been hampered by the lack of a reliable animal model. We recently discovered that treatment of rats from postnatal day 3鈥�18 with the glutamatergic agonist, homocysteic acid (HCA), leads to the development of manic and depressive behaviors in male and female rats. This model was developed based upon the clinical observation that elevated levels of the amino acid, homocysteine (HCY), are associated with the development of neuropsychiatric disorders. However, we reasoned that HCA, which is the oxidized metabolite of HCY, may actually dysregulate important glutamatergic pathways in the brain resulting in behaviors consistent with the bipolar phenotype. In order to provide strong construct validity to our new animal mode, we plan to directly test the hypothesis that elevated levels of HCY during the same critical period in developing rats will lead to an increase in HCA levels in the plasma and brain and the development of a mixed depressive/manic state. The specific goal for this summer is to complete the measurement of HCA and HCY levels in the plasma and brains rats exposed to high HCY during development. These data will analyzed in combination with our previous behavioral assessment of HCY treated rats so that we can better understand the link between HCA levels and the development of manic and depressive behaviors.

Principal Investigator
Dr. Maria Burnatowska-Hledin

This interdisciplinary project will incorporate the disciplines of chemistry and biology, and the project is specifically housed within the 暗网TV departments of biology and chemistry.

Research conducted in our lab focuses on elucidating the normal function for VACM-1/cul5, an endothelium specific gene product which shares sequence homology with cullins, a family of intracellular proteins that regulate diverse signaling pathways in response to changes in the cellular environment. Our work to date indicates that VACM-1 protein regulates cellular growth by a mechanism that distinguishes it from growth regulating factors, and from other cullins, and thus suggests a unique biological role for this largely uncharacterized protein. We have shown that both, in cancer cells and in endothelial cells, VACM-1 inhibits growth while expression of VACM-1 mutant has a dominant negative effect on cellular proliferation in vitro. Importantly, expression of VACM-1 mutant converts endothelial cells to the angiogenic phenotype. Consequently, VACM-1 may play a role as a potential novel suppressor of angiogenesis in vivo.

Thus, the goal of our recent research is to test the hypothesis that VACM-1 is involved in the regulation of endothelial cell growth, and to identify the mechanism of VACM-1 regulated angiogenesis in vitro. Specifically, we are examining the effects of posttranslational modification on the biological activity of VACM-1 and whether aberrant expression of VACM-1, or expression of mutated VACM-1 may lead to a disease, cancer in particular. Students will be involved in designing experiments that test different aspects of the structure-function properties of VACM-1. Students involved in our research projects will learn experimental procedures that include DNA isolation, site-directed mutagenesis, cell culture, immunocytochemistry, spectrophotometry, fluorescence polarization techniques, polyacrylamide gel analysis and Western blotting. Importantly, students will learn to read, discuss and question research papers effectively and to prepare scientific manuscripts.

Principal Investigator
Dr. Erika Calvo-Ochoa

This interdisciplinary project will incorporate the disciplines of neuroscience and biology. However, the project is specifically housed within the 暗网TV Department of Biology.

With this study, we will examine cellular and molecular mechanisms underlying neuronal regeneration and repair following damage in the olfactory system of zebrafish.

The olfactory system is composed of two peripheral olfactory organs located in the nasal cavity, and the olfactory bulb, a brain region that regulates olfactory information. This system allows organisms to detect odor signals and thus interact with their environment. Olfaction mediates behaviors pivotal for survival, such as feeding, mating, social behavior and danger assessment.

The olfactory system of zebrafish presents a remarkable degree of regeneration and neuroplasticity, making it an ideal model for the study of regeneration, reorganization and repair mechanisms following injury and disease.

We have discovered that lesions of the olfactory bulb produce neuron loss and degeneration in many components of the olfactory system, including the olfactory bulb and olfactory sensory neurons of the olfactory epithelium. This neuron loss and degeneration is followed by complete neuronal regeneration and repair. Moreover, we have shown that increased and sustained production of new neurons (i.e., neurogenesis) in a neighboring brain region known as the subventricular zone (SVZ), and in the olfactory epithelium following damage to the olfactory bulb.

Our main goal is to answer the following question: Is neurogenesis a central component of regeneration and repair in the lesioned olfactory bulb?

To answer this, we will study the timeline of neurogenesis and neuronal fate in the olfactory bulb by using different neuronal markers. This will allow us to track newly born neurons on route to the olfactory bulb, as well as the type of neurons they ultimately become (i.e., glutamatergic v dopaminergic).

We will also use a transgenic fish in which neuronal stem cells, which are neuroinflammatory cells (astrocytes) express a green fluorescent protein. This will allow us to track both neuroinflammatory responses in the olfactory bulbs following lesion, as well as activation of neural progenitor cells in the SVZ.

We will employ the following techniques: fluorescent immunohistochemistry, whole-mount 3D preparations of the olfactory bulb, and confocal microscopy.

Principal Investigator
Dr. Erika Calvo-Ochoa

This interdisciplinary project will incorporate the disciplines of neuroscience and biology. However, the project is specifically housed within the 暗网TV Department of Biology.

With this research project we will examine olfactory-mediated function and behavior following degeneration and regeneration of the olfactory system following a lesion in the olfactory bulb of zebrafish.

The olfactory system is composed of two peripheral olfactory organs located in the nasal cavity, and the olfactory bulb, a brain region that regulates olfactory information. This system allows organisms to detect odor signals and thus interact with their environment. Olfaction mediates behaviors pivotal for survival, such as feeding, mating, social behavior and danger assessment.

The olfactory system of zebrafish presents a remarkable degree of regeneration and neuroplasticity, making it an ideal model for the study of regeneration, reorganization and repair mechanisms following injury and disease.

We have discovered that lesions of the olfactory bulb produce neuron loss and degeneration in many components of the olfactory system, including the olfactory bulb and olfactory sensory neurons of the olfactory epithelium. This neuron loss and degeneration is followed by complete neuronal regeneration and repair.

In addition to the morphological regeneration and recovery observed in the olfactory system, it is not yet known if olfactory system degeneration caused by bulbar lesions cause olfactory dysfunction.

We aim to answer the following question: Does injury to the olfactory bulb results in olfactory dysfunction and alterations in olfactory-mediated behavior?

To answer this, we will study the timeline of olfactory function following lesion and during recovery using olfactory-mediated behavioral tasks. We will study the behavioral response to three different classes of odorants that convey important environmental signals: aminoacids (i.e., food), bile salts (i.e., kinship), and skin extract (i.e., alarm response). This will allow us to test whether lesioned fish present a reduced olfactory response to individual or all classes or odorants, and how this response is recovered.

We will use olfactory behavioral tasks and specialized software that allows for registering and analyzing animal behavior.

PRINCIPAL INVESTIGATOR
Dr. Leah Chase

This interdisciplinary project will incorporate the disciplines of biology, biochemistry and neuroscience . However the project is specifically housed within the 暗网TV Department of Chemistry.

Bipolar disorder is a serious mood disorder that is characterized by periods of depression and mania. The development of novel therapies for this disorder has been hampered by the lack of a reliable animal model. We recently discovered that treatment of rats from postnatal day 3鈥�18 with the glutamatergic agonist, homocysteic acid (HCA), leads to the development of manic and depressive behaviors in male and female rats. In addition, we did a follow up RNA microarray study in a few animals and discovered that nearly 200 genes are differentially expressed in the HCA-treated animals months after the initial exposure to HCA. We are now using a technique known as qPCR to validate these inital findings so that we can better understand how changes in gene expression lead to behavioral changes in these animals.

Students working on this project will learn the basic techniques associated with transcriptomics. Specifically, they will learn how to extract RNA from tissue, perform reverse transcription and qPCR reactions and analyze their data using various transcriptomics software packages.

Principal Investigator
Dr. Leah Chase

This interdisciplinary project will incorporate the disciplines of biology, chemistry and neuroscience. The project is specifically housed within the 暗网TV departments of biololgy and chemistry. Therefore, interested students can elect to participate in either summer research program.

In living organisms, routine metabolic processes result in the formation of many free radicals within the cellular environment that can be toxic to the cells themselves. My research tests the hypothesis that free radicals produced in metabolism regulate a membrane transport system, System xc-, that provides neurons and glia with the precursors required to synthesize a cellular antioxidant called glutathioine. System xc- is a plasma membrane transport system that catalyzes the stoichiometric exchange of extracellular cystine for intracellular glutamate in the brain. The internalized cystine is then used for glutathione synthesis which protects the brain from oxidative damage. While several groups have demonstrated transcriptional regulation of System xc- within 24 hours of exposure of cells to oxidants there have been essentially no studies which have examined the short-term regulation of transporter activity. My students and I have shown that oxidants appear to acutely (within minutes) regulate System xc- by modulating the cell surface expression of the transporter. These exciting findings suggest a novel form of regulation of System xc- that may serve as an extremely important component of the cellular defense system in protecting cells from oxidative insults. We are currently using biochemical and molecular techniques:

To identify important trafficking motifs within the C-terminus of System xc-, and
To describe the cellular signaling pathways that are involved in the hydrogen peroxide-regulated activity of System xc-

Ultimately, this work will provide us with a better understanding of molecular processes which acutely regulate System xc- and identify key proteins which regulate transporter trafficking. As such, this work may provide direction for future studies aimed at pharmacological manipulation of System xc- activity for therapeutic benefit.

Each student in the Chase lab has their own independent research project that fits into the overall research aims of the lab. Students also assist in formulating testable hypotheses and constructing appropriate experimental designs to test their hypotheses.

Principal Investigators
Dr. Natalia Gonzalez-Pech and Dr. Kelly Ronald

This interdisciplinary project will incorporate the disciplines of biology, neuroscience, psychology, chemistry and materials science. However the project is specifically housed within the 暗网TV Department of Biology.

There is great concern regarding the adverse health implications of engineered nanoparticles. However, there are many circumstances where the production of incidental nanoparticles (i.e., nanoparticles unintentionally generated as a side product of some anthropogenic process) is of even greater concern. These nanoparticles can transport through the respiratory system and translocate to other organs, including the brain. The health implications of this transport has been study in in-vitro systems and animals models like mice, but never in birds. Birds should be an interesting model as they can be more exposed to the incidental nanoparticles present in air. This project will examine both the visual and auditory sensory processing of the song bird the house sparrow (passer domesticus). House sparrows frequently occupy a variety of human dominated environments and therefore span the gradient of noise and light pollution areas.

Principal Investigator
Dr. Jianhua Li

The anthropogenic CO2 released into the atmosphere has increased steadily in recent decades causing and enhancing global climatic changes with extraordinary impact on organisms including humans. Mitigating the impact requires actions such as the increase of carbon sequestration via the greening of the Earth. Plants are major carbon storage or sink with trees and shrubs being the most effective. However, mechanisms for carbon sequestration at the genomic level remain to be explored. My lab will use genomic approach to explore genetic changes associated with the differential carbon sequestration among trees and shrubs. The project help us to gain deep understanding of changes of ecosystems from large to minute scales.

Principal Investigator
Dr. Jianhua Li

This interdisciplinary project will incorporate the disciplines of ecology, plant genomics, and evolution. Flowering plants or angiosperms are the most diverse plants in the world with over 250,000 species and are characterized by producing flowers and fruits. Those structures are initiated after a certain period of vegetative growth and development, however, when the switch to reproductive growth is initiated varies across the plant groups. Some plants do this within a few month, while others may take many years or decades. What factor(s) control the switch: ecological, genetic, or the combination of the two? If we know the factors, can we control the factors and in turn the plant flowering at will in space and time? We will use anatomical and genomic approaches to explore the questions.

Principal investigator
Dr. Virginia McDonough

This interdisciplinary project incorporates the disciplines of biology and chemistry. However, the project is specifically housed within the 暗网TV Department of Biology. This project is only open to 暗网TV students.

Problems with the regulation of lipid metabolism contribute to many chronic human disorders including heart disease, diabetes, obesity, and even some cancers. The long-term goal of the work is to gain a better understanding of the regulation of lipid production by dietary fats. We focus on one enzyme, the stearoyl-CoA fatty acid desaturase, which is encoded by the OLE1 gene in the model organism Saccharomyces cerevisiae. The desaturase produces monounsaturated fatty acids from saturated precursors. It is strongly regulated by the availability of fats in the diet. While aspects of the regulation are understood, it is far from complete: cells regulate expression of OLE1 through the ER resident transcription factors Mga2p and Spt23p. These proteins are switched on from an inactive p120 form to an active p90 form, which translocate into the nuclease and activate transcription of OLE1.

What signal causes Mga2p and Spt23p to be switched from 鈥渙ff鈥� to 鈥渙n鈥�? What proteins are involved in these processes? How do cells sense the type and presence of fed fatty acids? The overarching hypothesis of this work is that fed fatty acids are trafficked to internal membranes where protein sensors recognize and communicate the status of the membrane to these regulators of OLE1 gene expression. The objective of the work this summer will be to identify the signals and gene products that regulate expression of OLE1, and how they work.

Students working on this project will use both molecular genetic and biochemical approaches in their work. Experimental procedures will include some or all of the following: cell culture, cloning, DNA isolation, PCR, qPCR, gel electrophoresis, spectrophotometry, reporter gene assays, protein-protein interactions using 2 hybrid analysis, western blotting, GC and GC-MS, and microscopy. In addition to experimentation, students will be expected to be full members of the research team-analyzing data, preparing figures, reading and discussing research literature, and to present their results at a scientific conference.

Principal Investigators
Dr. Greg Murray and Dr. Elizabeth Sanford

This interdisciplinary project will incorporate perspectives from both biology and chemistry to elucidate the basis of chemical defense in tropical pioneer plant seeds. It is specifically housed within the 暗网TV Department of Biology, but student investigators will work closely with both Dr. Murray (biology) and Dr. Sanford (chemistry). It is open only to 暗网TV students who are already working in the Sanford or Murray labs.

Tropical rainforests are legendary for their biological diversity and for the complexity of interactions among their species. The interactions between animals and plants are especially prominent 鈥� animals are important as pollinators, seed dispersers and seed predators, and plants are under strong selection pressure to reinforce the positive interactions with animals and to weaken the negative ones. 鈥淧ioneer鈥� plants 鈥� those that specialize on colonizing recently disturbed patches of forest but which cannot compete in the shaded understory 鈥� constitute a model system in which to study tropical plant-animal interactions because their seeds must survive in the soil for years despite intense threats from both animals and pathogenic fungi. Our research group seeks to understand how seed dispersers, seed predators, microbial pathogens, and physical disturbance interact to influence the demography of tropical pioneer plants and thus the maintenance of forest structure and species composition. We are especially interested in questions that encompass several levels of biological organization, or that combine the approaches of other disciplines (e.g., mathematics, computational science and organic chemistry) with those of ecology. This summer, we will continue our characterization of the chemical defenses of pioneer plant seeds, focusing on species whose seeds can survive for decades in tropical soils, despite threats from seed-eating animals and microbial attack. Students involved in this research will employ a variety of extraction, chemical separation and analysis techniques, as well as toxicity bioassays against fungi and arthropods. They will also gain experience in hypothesis formation and statistical analysis, in analyzing the scientific literature critically, and in presenting their research results in written and oral formats.

Principal Investigator
Dr. Kelly Ronald

Alcohol during pregnancy is a well known disrupter of neonatal central nervous system (CSN) development. Within the CNS, resident immune cells (i.e., microglia) are primed by alcohol which leads to aberrant phagocytosis of neurons. Nevertheless, it is still unknown whether microglial activation leads to abnormal vocalization patterns. Therefore, pregnant dams were allowed to binge on 20% alcohol on embryonic day 15鈥�20. After partition the vocal behaviors of pups born to addicted dams were assessed on postnatal days (PND) 4, 7 and 9. In addition, maternal care behavior was assessed by examining nest construction. Pups are allowed to mature and will be assessed in adulthood for addiction-like behaviors including drinking-in-the-dark and ethanol condition place preference. All behaviors will be assessed in both males and females to test for sex-effects. Likewise, the microglia response in the dentate gyrus in the hippocampus will be determined in a sex-dependent manner.

Principal Investigator
Dr. Kelly Ronald

This interdisciplinary project will incorporate the disciplines of biology, neuroscience and psychology. However the project is specifically housed within the 暗网TV Department of Biology.

Anthropogenic disturbances have long changed the dynamics of our ecosystems and habitats. Alongside this change in the physical environment comes alterations of both the environmental light and sound profiles. New research has shed light on the strategies that animals use to signal in environments that are dominated by sound and light pollution. For example, there is repeated evidence to suggest that birds in urban areas sing at higher-frequencies to avoid masking by lower-frequency traffic noise. Less is known, however, about whether signal receivers differ in their visual and auditory physiology as a result of noise and sound pollution. As communication involves both the successful production of signals as well as the successful reception of these signals, it is imperative that we examine receiver sensory processing as a function of anthropogenic disturbance. This project will examine both the visual and auditory sensory processing of the song bird the house sparrow (passer domesticus). House sparrows frequently occupy a variety of human dominated environments and therefore span the gradient of noise and light pollution areas. We would predict that house sparrows captured in areas with greater human disturbance might show better high frequency hearing than animals captured in more rural areas; additionally, we might also expect that visual temporal resolution (e.g., the ability to of detect motion) will differ between the two populations. Studies examining the effects of human disturbance on receiver sensory processing are vitally important to developing efficient and effective conservation efforts.

Students involved in this project will be involved in both field and lab techniques including auditory and visual recordings in the field, animal handling and capture, and physiological experiments (auditory and visual evoked potential recordings) in the lab.

Principal Investigator
Dr. Joseph Stukey

A bacteriophage, or more simply phage, is a virus that infects bacterial cells. Research in my lab is focused on understanding basic mycobacteriophage biology and more broadly, phage genome evolution. Mycobacteriophages are phages that infect the bacterial genus, Mycobacterium.

I have multiple projects in various states of completion or conception, including:

Identify and characterize phage-host intracellular interactions at the molecular level. We have identified multiple genes in two different mycobacteriophages that impair growth of M. smegmatis when expressed as individual genes. We have preliminary data indicating that for many, the expression of the phage gene results in enlarged cell growth, suggesting the phage protein may interfere with cell division processes. Future research goals include further examining the impact of cytotoxic phage gene expression on host cell growth using a variety of methods including cell staining and microscopic visualization, and testing whether the identified cytotoxic phage gene is essential to the phage during infection.
Investigate the biology of a subset (Cluster K) of mycobacteriophages known for their general ability to infect a broad range of mycobacterial hosts, often including the pathogen, M. tuberculosis. We are investigating growth features of several distinct subgroups of Cluster K1 phages, which may relate to differences in host preference. Our current findings suggest a subset of K1 mycobacteriophage are optimized for growth at lower temperatures and are well-adapted to an environment with a low host density. We believe there is a link between these growth features and the ability of cluster K mycobacteriophages to recognize a broader range of hosts. This project is near completion.
Investigate phage genome evolution. This project seeks to better understand the similarities and differences in genome structure and gene content across known mycobacteriophages, and to address questions on the nature and function of the evolutionary mechanisms that generate the observed genome architecture and genetic diversity. To address these questions, we have designed and constructed pairs of modified phage genomes, that differ in the presence/absence of specific coding information. We have just started testing the specific pairs for impacts on phage growth using a variety of different assays. This work may help us understand how genetic diversity, prevalent in phage genomes, is generated, as well as better understand the modular nature of phage genomes.
Investigate how mycobacteriophages recognize and 鈥渋rreversibly鈥� bind to host cells, including identification of phage receptor binding proteins and corresponding host receptor components, and then transfer their DNA into host cells at initiation of infection.

All research projects employ a combination of microbiological, molecular, biochemical and bioinformatic methods of analyses.

Our findings will provide new and important information on the molecular biology of phage-host cell interactions from mycobacterial host selection through mycobacteriophage infection and a better understanding of the evolution of mycobacteriophage genomes.

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Faculty Research

OFF CAMPUS RESEARCH

GENERAL, MULTI-FIELD SITES (ACROSS SCIENTIFIC DISCIPLINES)

EPIDEMIOLOGY/BIOMEDICAL/GENETICS

ECOLOGY/CONSERVATION/WILDLIFE/MARINE BIOLOGY

PLANT BIOLOGY

Miscellaneous