Mark A. Sheridan - US grants

This proposal requests funds for the purchase of an ultracentrifuge, high-speed centrifuge, and rotors for each. This equipment will benefit four investigators in the Departments of Botany/Biology and Zoology who are engaged in research on: isolation and characterization of photosynthetic pigment-protein complexes from algae, regulation of the biogenesis of light- harvesting chlorophyll-protein complexes, hormonal regulation of lipid metabolism in fish, and nitrogen metabolism of plant cell suspension cultures, regeneration of plant cell cultures. This instrumentation will provide an important stimulus to a group in the process of building a synthetic program in modern plant biology.

In this study the action and interaction of hormones on lipid (fat) metabolism, particularly lipid metabolism in liver will be investigated. The liver is an important organ in animal metabolism, however, little information exists concerning its role as a fat store. Fish (chinook salmon, rainbow trout), which have a unique ability to store lipid in their liver, are the model for these studies. Initial investigations will focus on the actions of various pancreatic hormones (insulin, glucagon and somatostatin) in the whole animal. The metabolic action of a particular hormone as well as the interaction of that hormone with other hormones will be examined. The relationship between aspects of lipid metabolism and alteration in carbohydrate metabolism as well as the biochemical processes operating within the liver cell will be examined to determine the mechanisms by which pancreatic hormones influence lipid metabolism.

9305554 Sheridan Recent studies have indicated the existence of multiple forms of somatostatin, a peptide originally isolated from the brain and found to contain 14-amino acid (from gene I) and to inhibit growth hormone secretion, but subsequently found to be located in the pancreas, gastrointestinal tract and elsewhere of many vertebrates. The special significance of multiple forms (14-amino acid forms and N-terminally extended forms) of somatostatins, and the roles of these factors in regulation of lipid metabolism, have yet to be determined. With the proposed work, Dr. Sheridan seeks to evaluate the role of somatostatins in the coordination of lipid metabolism in fish. Fish offer a unique system for the study of these questions because of their evolutionary position, diversified lipid storage strategy (partitioning of lipid reserves among several depots: mesenteric fat, liver and dark muscle), and segregated endocrine pancreas (Brockman body) possessing abundant amounts of N-terminally extended somatostatin (somatostatin-25; from gene II). He will demonstrate for the first time the differential effects of gene I and gene II somatostatins on lipid metabolism. This analysis will demonstrate important interactions among the various pancreatic hormones (e.g., somatostatins, insulin, glucagon, pancreatic polypeptide) and evaluate the direct effects, including cellular mode of action, of somatostatins on hepatic lipolysis. He also will evaluate for the first time the binding of somatostatin to liver, a major lipid depot of fish, and examine alterations in somatostatin binding characteristic (affinity, capacity) in response to nutrient (glucose) and hormonal (INS, GLU) treatment. While pertaining specifically to fish, this research will provide novel information concerning somatostatin phsyiology generally. These results will contribute significantly to the basic understanding of hormonal control of hepatic lipid metabolism and provide important insight into the evolution of lipid metabolism control schemes. ***

9406707 Sheridan It is well known that the pancreas produces hormones that regulate such critical processes as metabolism, development, and growth. The best known pancreatic hormones are insulin and glucagon. Recent studies have shown the existence of multiple forms of somatostatin, a peptide hormone originally isolated from the brain and found to inhibit growth hormone release from the pituitary gland, but subsequently found to be located in the pancreas, gastrointestinal tract, and elsewhere of many animals. The special significance of the multiple forms of somatostatin and the roles these factors play in coordinating aspects of metabolism, growth, and development remain to be determined. With this project, Dr. Sheridan will evaluate how somatostatin influences, directly and/or indirectly (via interactions with other pancreatic factors such as insulin), lipid metabolism in fish. Specifically, he will determine in what tissues and through what specific cellular processes somatostatin influences fat uptake and breakdown. In addition, he will distinguish the actions of two pancreatic somatostatin forms (the co- existence of which is unique to fish). These results will contribute significantly to the overall understanding of how metabolism is regulated and provide important insight into the evolution of somatostatin action. ***

9723058 Sheridan Somatostatins are a relatively diverse family of peptide hormones known to affect a wide array of biological processes, including growth, development, and metabolism. Despite the significance of the group of hormones, little is known about their evolution or about the mechanisms which control the genes that encode them. With this project, the PI will use a simple model system, rainbow trout, to examine fundamental aspects of somatostatin gene expression. He will provide for the first time a definitive analysis of the polygenic origin of somatostatins. He will characterize the expression of alternate forms of somatostatins and investigate how somatostatin gene expression is controlled by various environmental and endogenous (i.e., other hormones such as insulin) factors. While this research pertains specifically to fish, it will provide important new insight into the evolution of the somatostatin gene family and yield novel information with board relevance to the understanding of somatostatin-mediated control of growth, development, and metabolism.

9809909 Sheridan Hormones of the gastoenterpancreatic system play an important part in regulating the growth, development, and metabolism of animals. This symposium will bring together scientists fro molecular biology, cellular biology and organismal biology to provide an integrated synthesis of the function and evolution of this important group of chemical mediators in vertebrate and invertebrate organisms. This symposium is in honor of Dr. Erika Pisetskaya, Research Professor Emeritus, who has had a long and distinguished career and who has contributed so much to the fields of comparative endocrinology and comparative physiology/biochemistry. The symposium will have both oral and poster sessions. Ten invited speakers will deliver oral presentations while postdoctoral fellows or graduate students fro the laboratories of each of the speakers will present posters as a means to encourage the participation of young scientists. The proceedings from the proposed symposium will be published in the American Zoologist by a peer review process. Dr. Sheridan hopes to foster a broader discussion and integrated synthesis of the comparative structures and functions of these chemical mediators in invertebrate and vertebrate organisms. In addition, the relationship of the hormones of the enteropancreatic systems will be discussed in relationship of these factors and hormones in other systems will be discussed in relationship of these factors and hormones in other systems such as the central nervous system.

EPSCoR will build science, engineering and mathematics (SEM) infrastructure in North Dakota that will 1) increase competitiveness for merit-based grants and contracts; 2) improve research productivity; 3) increase the rate and quality of technology transfer from university originated research to the private sector in North Dakota, and, 4) enhance the development of human resources in North Dakota. A three pronged competitive grants program designed to improve research competitiveness and productivity will be conducted that includes: 1) a program in which Chairs and Deans compete for funds to improve their ability to hire top quality faculty, 2) peer-reviewed seed grants for new principal investigators, and, 3) a graduate student enhancement program designed to increase research productivity as well as the number of graduates from SEM areas. The project will also conduct a multi-component human resources program designed to achieve the following goals: 1) increase the opportunities available for students of the North Dakota University System to participate in research; 2) increase the numbers of members of underrepresented groups involved in SEM research activities will be implemented. Undergraduate research and mentoring programs for the summer months and academic year, which target underrepresented groups, will be continued and upgraded. These include programs designed in consultation with North Dakota's Tribal Community Colleges and a new program targeting potential women scientists and another geared to facilitate the transition from high school science activities to undergraduate research programs.

Somatostatins (SS) are a diverse family of peptide hormones that control
animal growth, development, and metabolism. Despite the importance of this
hormone family, little is known about the basis of its multi-functional
nature. In particular, it is not known how the hormones and their
receptors interact to elicit a specific effect in a particular target cell
or how the structural heterogeneity of the SS family influences such
interactions. With this proposed work, the unique situation in teleost
fish such as rainbow trout, which possess multiple SSs, will be exploited
to examine fundamental aspects of SS-receptor interactions. The hypothesis
that rainbow trout possess multiple SS receptors with differential ligand
selectivity that are differentially expressed will be tested in four
experimental phases. In phase I, multiple mRNAs encoding distinct SS
receptors will be characterized. In phase 2, the binding characteristics
of expressed SS receptors will be examined. In phase 3, the distribution
and abundance of SS receptor mRNAs will be determined. In phase 4, factors
(e.g., nutritional state, insulin) that control the expression of SS
receptor mRNAs will be identified. While this work pertains specifically
to fish, it will provide important new insight regarding linkage between SS
receptor type to a specific biological action and have broad relevance to
understanding the multi-functional nature of SS.

The North Dakota "Advancing Science Excellence in North Dakota (ASEND)" initiative is aimed at expanding the research capacity of North Dakota and to strengthen its ability to participate in the nation's mainstream science, engineering, and mathematics (SEM) enterprise. This initiative capitalizes on North Dakota's existing research strengths and takes advantage of opportunities to integrate research into education and into the economy of the state. The ASEND initiative will develop SEM infrastructure at North Dakota State University (NDSU) and the University of North Dakota (UND)

North Dakota (ND) will focus on three research areas: catalysis, biocomplexity and multisensory integration. Each of these areas has been identified as niche to the state and contributing to national interests. In the area of catalysis, an interdisciplinary network of researchers will build on ND's current expertise in polymers and combinatorial chemistry to develop novel processes and materials, particularly those with technology transfer/commercialization potential. The biocomplexity focus area will concentrate initially on the influence of parasitism on biocomplexity. An interdisciplinary team of researchers will investigate the role of parasites on host population genetics, landscape ecology, sexual selection, host bioenergetics, biodiversity and evolution. The multisensory integration research area will bring together cognitive and sensory psychologists with neurophysiologists to study sensation, perception, cognition and action. Researchers will investigate the sites, structures and processes of neural activity associated with multisensory integration. Potential applications include the development and evaluation of virtual environments.

In addition to the research efforts, the ND project includes a multifaceted human resource development program designed to increase the opportunities available for students of the ND University System to participate in research and to increase the number of members of underrepresented groups (e.g., low income, first-generation college, women, Native Americans) involved in SEM research activity. Moreover, a technology transfer program designed to facilitate academic-private sector partnerships and integration of research into the economy of the state will be implemented. The technology transfer effort includes programs linking undergraduate students, graduate students and faculty with local industries and a commercial feasibility support program.

This award supports purchase of a confocal microscopy system, including camera and computer for research and teaching in cellular and molecular biology, endocrinology, reproductive physiology, digestive physiology, animal embryology and nutrition. This system will permit high-magnification, high-resolution studies employing bright field, differential interference contrast (DIC) and epifluorescence microscopy. The state-of-the-art confocal system and infinity optics in this microscope will enhance quantitative immunofluorescence studies. The three investigators who will share the microscope have research programs focused on the role of vascular development (angiogenesis) in tissue growth, development and regression; hormonal control of growth, development and metabolism; and cellular interactions within organs and tissues. Other researchers from the Cell Biology Center and the Departments of Animal and Range Sciences, Biological Sciences, and Veterinary and Microbiological Sciences, as well as their students, are also expected to use the system.

ABSTRACT NOT PROVIDED

The coordination of organismal growth involves the integration of many external and internal cues that result in the production of numerous hormones and growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I). An understanding of how the various cues are integrated and how the interplay of hormones modulate growth is far from complete.
In this project, rainbow trout will be used as a model organism to evaluate the effects of somatostatins (SSs), a multi-functional family of peptide hormones, on the growth control network. Research will reveal the influence of SSs on GH responsiveness in selected cell types (e.g., liver). This will involve the characterization of GH receptors (GHR) and an analysis of the effects of SSs on GHR expression. Research also will elucidate the influence of SSs on IGF-I synthesis and secretion. In addition, the effects of SS on IGF-I responsiveness in selected cell types (e.g., muscle) will be determined. This will involve an analysis of IGF-I binding characteristics and of IGF-I receptor expression. Lastly, the mechanisms of SS action will be characterized by identifying signal pathways through which SSs operate and by establishing which SS receptor subtype activates which signal pathway. The results of this project will advance our understanding of normal growth control processes and have application to efforts to improve growth efficiency of fish (e.g., aquaculture), poultry and domestic livestock, as well as to the detection and treatment of growth disorders in animals and humans. In addition, the project will expand critical research infrastructure in North Dakota, serving to diversify the nation's scientific enterprise, and afford research education and training opportunities to undergraduate and graduate students, including members of underrepresented groups.

The means by which hormones elicit multiple effects in animals remains a central question in the field of chemical signalling. For example, growth hormone (GH) is known to regulate several processes, including aspects of growth, metabolism, reproduction, osmoregulation, immune function, and behaviour, yet the mechanisms that underlie these diverse processes are not fully understood. In this project, rainbow trout will be used as a model organism to evaluate two disparate actions of GH: 1) growth promotion, an anabolic process, and 2) breakdown and mobilization of stored lipid reserves (lipolysis), a catabolic process. Fish such as trout provide an opportune system in which to examine this problem because they grow throughout their life (indeterminate growth) and display a diverse lipid storage strategy that results in the colocalization of important growth-promoting [i.e., insulin-like growth factor-1 (IGF-1) synthesis and secretion] and lipid storage/lipolysis processes within the same cell types (e.g., liver cells, a main lipid store as well as the principal site of IGF-1 synthesis). The 4-year plan of work will integrate several approaches (e.g., physiological, cellular, biochemical/molecular/ genomic) and address the problem in three phases. In the first phase, we will characterize GH receptor (GHR) binding properties and assess its selectivity for different hormones that are structurally similar to GH (e.g., prolactin). In phase 2, we will identify the cell signal pathways activated by GH and how these pathways are reprogrammed by an anabolic to catabolic shift. This will establish GHR-effector pathway linkages. In phase 3, we will elucidate linkages between signal pathways and specific biological responses, and specifically evaluate differential activation of growth-promotion (e.g., IGF-1 production) and lipolysis. This project will fundamentally advance our understanding of the coordination of growth and metabolism by elucidating for the first time the means by which cells get reprogrammed to repress the growth-promoting actions of GH to enable its lipolytic actions. In addition, this project will provide novel information about the mechanisms by which GH stimulates lipolysis (via hormone-sensitive lipase activation and/or synthesis) and about the regulation of GHRs and GHR-effector system linkages. While this work pertains specifically to fish, it will have broad relevance to understanding the nature and evolution of growth-metabolism interactions in vertebrates generally. This project will have numerous other broad impacts. It will expand critical research infrastructure in North Dakota, which serves to diversify the nation's scientific enterprise. It also will afford research education and training opportunities to graduate and undergraduate students, including members of underrepresented groups. The project will specifically engage faculty and students of the state's tribal colleges through curriculum development, workshops, and summer camps. These activities that will lead to a collaborative student-centered research project at a tribal college. The findings also will have application to enhancing agricultural production of fish, poultry, and domestic livestock, as well as to the detection and treatment of various growth/metabolic disorders in animals and humans.