Gregory S. Fraley - US grants

DESCRIPTION (provided by applicant): The overall goal of this proposal is to understand more about the physiology of galanin-like peptide (GALP) neurons, and particularly within the context of diabetes. The primary aims are 1) to determine the anatomical organization of GALP neurons with respect to other known neuroendocrine mediators of reproduciton and feeding and to learn wether this circuitry is altered in the diabetic state; and 2) to explore the role of GALP in mediating the effects of leptin and insulin on the reproductive system, by examining the effects of centrally administered GALP on the reproductive axis and behaviors in a rodent model of type I diabetes. All experimental manipulations will be carried out in the diabetic male rat and compared to normal controls. Diabetic status will induced pharmacologically with subcutaneous injections of streptozotocin at a dose known to induce diabetes in at least 95% of animals without altering glucocorticoid levels. Control animals will be injected withvehicle. To accomplish these goals, the use of various neuroanatomical techniques, including retrograde tract-tracing combined with single- and double-label immunocytochemistry, will be used to map the hypothalamic circuitry linking GALP to other neurotransmitter systems in the hypothalamus. Analysis of male-specific sex behaivors following intracerebral injections of GALP and/or galanin will provide evidence for the role of these neuropeptides in the regulation of reproductive behaivors. Furthermorequantitative in sity hybridization will be used to determine the effects of hormonal and behavioral manipulations on GALP mRNA within the hypothalamus. It is hoped that this basic knowledge will lead to a better understanding of disorders of reproduction that are associated with diabetes and thus provide an enlightened path towards their treatment.

A grant has been awarded to Hope College under the direction of Dr. Leah A. Chase to acquire a digital imaging system that will be used by biology and chemistry faculty in their research and teaching. The new microscope will provide better imaging of cells in studies of cell trafficking of proteins in brain tissue, movement of free fatty acids in brain cells, and effects of the brain on nutrition and reproductive viability. The imaging system allows for improved visibility of cells and their internal structures labeled with fluorescent markers. The instrument will be used in several classes, in particular those in a new neuroscience minor in the Biology Department. In addition, the imaging system will enhance the summer instructional program, which has recruited a large number of students from outside the Hope College campus, including a significant number of students from minority and underrepresented populations.

Hope College (Holland, MI) will host an REU Site each summer for the next 5 years (2008-2012). Students will conduct research on "Environmental Impacts on Biological Systems: From Molecules to Ecosystems," with faculty in the Biology Department. Students will develop a deeper understanding of the integrative nature of biology and of the role of the environment in biological processes and on biological systems. Students will generate experimental hypotheses, design and carry out experiments, evaluate data, and communicate their results to both scientific and non-scientific audiences. Students will also gain insight into linkages across different scales of biological systems, while conducting research at the level of biological organization in which they are most interested. Students will learn lab techniques and use of the scientific literature, participate in weekly workshops, discuss ethics in science, and get exposed to various careers in science. At the end of summer, students are expected to be experts in the background, methods, results and significance of their research work and are prepared to present their work at professional scientific meetings. The goal is to develop students into independent and highly competent young scientists who are well-prepared for graduate study in biology and careers as research scientists. REU students are provided with a stipend, no cost housing, and funds for travel to and from Hope College. Students belonging to groups underrepresented in the biological sciences are strongly encouraged to apply. More information is available at http://sharp.hope.edu/, or by contacting the Program Director (Christopher Barney) at barney@hope.edu.

DESCRIPTION (provided by applicant): Food intake is regulated by numerous brain structures, particularly within the hypothalamus. One hypothalamic structure, the dorsomedial nucleus (DMN), is known to regulate food intake. A recently described neuropeptide in birds, gonadotropin inhibitory hormone (GnIH), inhibits reproduction and stimulates food intake. In mammals, a related neuropeptide has been described in the DMN and identified as GnIH-3. GnIH-3 shows a strong effect to increase food intake in rats. Little to no attention has been given to the neural mechanisms underlying GnIH-3's effects on food intake. In rats, central treatment of GnIH-3 increases hypothalamic neuropeptide Y (NPY) and growth hormone releasing hormone mRNAs. Increased NPY is known to stimulate food intake. It is not known, however, if GnIH-3 increases NPY directly or if it increases NPY via increased levels of circulating growth hormone (GH); nor is it known if GnIH-3 stimulates other hypothalamic neuropeptides that regulate food intake. Thus the objectives of this application are first to determine the phenotype of neurons that are downstream targets of GnIH-3. Second, this application seeks to determine if GnIH-3 has the potential to act directly upon NPY neurons by deducing if NPY neurons co-express the GnIH-3 receptor. Third, this study will determine a causal link between GnIH-3- induced GH release and the increase in hypothalamic NPY mRNA. Thus the innovation of this application is that it seeks to understand the poorly understood role of GnIH-3 within the DMN to regulate food intake. GnIH-3's effects on food intake are described in every species examined, but the neural circuitry that modulates this effect has, as yet, not been investigated. The broader scope of this application lies in the training of undergraduate students. The proposed experiments combine behavioral, surgical, histological, anatomical, and molecular biological techniques. This combination of techniques illustrates to trainees the interdisciplinary aspects to neuroscience and helps prepare them for post-baccalaureate education. Furthermore, Hope College's mission towards Teaching Through Hands-on Research gives my students an opportunity to be in the laboratory, to perform research, to write scientific papers and to present data at national meetings. Students even have the opportunity to do a small amount of teaching if desired. The majority of students in my laboratory over the last 7 years have been women and/or from under-represented groups.