Robert Steiner - US grants

The goal of this research proposal is to develop a greater understanding of the physiological mechanisms that control the onset of puberty in the primate. Using the male monkey, Macaca fascicularis, as a model for studying this problem, we will focus our efforts toward resolving how the body's metabolic control systems interact with its reproductive elements. This relationship is important, because we know that factors such as body weight and composition, metabolic rate, and nutritional status are intimately linked with pubertal maturation in human beings. First, we will examine the thesis that substrate-limited pathways of brain metabolism act to control luteinizing hormone-releasing hormone (LHRH) and gonadotropin secretion. We propose that changes in an animal's metabolic status, occurring as a function of life stage, is reflected in alterations in circulating metabolic hormones and substrates, which, in turn, serve as either signals or essential precursors for the synthesis of neurotransmitters engaged in regulating the LHRH pulse generator. Our specific aim will be to identify these humoral factors and to elucidate their mechanisms of action. We suggest that this interaction between the metabolic and reproductive control systems and the resulting permissive influence on LHRH and gonadotropin secretion may be determinative in initiating the onset of puberty in primates and may also help to explain the etiology of reproductive failure associated with metabolic disorders and undernutrition in human beings. Second, using immunocytochemical and monoamine histofluorescence techniques, we propose to map the distribution and concentration of LHRH and catecholamine pathways in the medial basal hypothalamus of the developing monkey. Our specific aim is to identify changes in the neuroanatomical substrate, which may occur as a function of pubertal brain maturation. Together, these studies may help to foster a better understanding of human reproduction and could offer more insight into the clinical management of infertility.

Our primary goal is to learn about the basic neuroendocrine mechanisms controlling the reproduction in the male primate. We propose to use in situ hybridization for GnRH mRNA to study the physiological control of GnRH gene expression within individual neurons in the brain of the male macaque, Macaca fascicularis. We have plotted 4 major areas of investigation. The first concerns steroid hormone feedback. Testosterone serves a major role in the feedback control of GnRH secretion in the male primate, but the cellular mechanisms mediating this process remain obscure. In this aspect of the proposal, we will focus on determining whether gonadal hormones, and testosterone in particular, influence the level of GnRH mRNA in the brain; in addition, we will attempt to ascertain whether endogenous opioid pathways are involved in this negative feedback system. The second part concerns development. In primate species, the maturation of the reproductive system awaits only the augmentation of GnRH secretion, but the cellular mechanisms underlying the pubertal awakening of GnRH secretion are still unresolved. In this aspect of the proposal, we will focus on determining whether increases in GnRH mRNA can be implicated in controlling the onset of puberty in the primate. The third part concerns the problem of metabolic stress. Nutritional and metabolic status can have a profound influence on the secretion of GnRH in primates, but again, the cellular mechanisms mediating these disturbances remain unknown. We will attempt to ascertain whether changes in GnRH mRNA are responsible for changes in GnRH secretion caused by alterations in metabolism and to elucidate the possible role of glucocorticoids and corticotropin-releasing hormone in this process. Fourth, we will try to improve the methodology for conducting in situ hybridization analysis of GnRH mRNA in the brain. We believe this work will foster a better understanding of basic cellular neurobiology and help us to understand more about clinical problems related to human reproduction.

Funds have been provided for the purchase of a high performance static spectrofluorometer for shared use by a group of investigators. The instrument will be used for four different projects involving proteins, each of which utilizes fluorescence as a technique. Fluorescence intensity measurements will be used as a means of monitoring such processes as protein-protein and protein-nucleic acid interactions, ligand-induced conformational changes, and accessibility of fluorophors to quencher. Measurements of fluorescence anisotropy will also be used to study protein associations and conformational changes. Fluorescence energy transfer will be employed as a "spectroscopic ruler" to measure the separation of sites on a protein. Studies of the above kinds require an instrument with high sensitivity and stability, low background, and capability of providing corrected spectra. The individual projects are concerned with the properties and interactions of the Ca2+-binding regulatory proteins calmodulin and troponin C, the nature of the catalytic site of papain, the characteristics of nucleic acid-unwinding proteins, and the properties of the topoismerase enzymes which mediate alterations in the geometry of DNA. A central goal of molecular biology is to elucidate the structure of specific molecules and determine how their chemical characteristics influence their activity. One approach is fluorescence spectroscopy, which provides data about molecular subgroups and molecule-molecule interactions. This kind of information explains biological processes at their most basic level.

Our primary goal is to learn about the basic neuroendocrine mechanisms controlling the reproduction in the male primate. We propose to use in situ hybridization for GnRH mRNA to study the physiological control of GnRH gene expression within individual neurons in the brain of the male macaque, Macaca fascicularis. We have plotted 4 major areas of investigation. The first concerns steroid hormone feedback. Testosterone serves a major role in the feedback control of GnRH secretion in the male primate, but the cellular mechanisms mediating this process remain obscure. In this aspect of the proposal, we will focus on determining whether gonadal hormones, and testosterone in particular, influence the level of GnRH mRNA in the brain; in addition, we will attempt to ascertain whether endogenous opioid pathways are involved in this negative feedback system. The second part concerns development. In primate species, the maturation of the reproductive system awaits only the augmentation of GnRH secretion, but the cellular mechanisms underlying the pubertal awakening of GnRH secretion are still unresolved. In this aspect of the proposal, we will focus on determining whether increases in GnRH mRNA can be implicated in controlling the onset of puberty in the primate. The third part concerns the problem of metabolic stress. Nutritional and metabolic status can have a profound influence on the secretion of GnRH in primates, but again, the cellular mechanisms mediating these disturbances remain unknown. We will attempt to ascertain whether changes in GnRH mRNA are responsible for changes in GnRH secretion caused by alterations in metabolism and to elucidate the possible role of glucocorticoids and corticotropin-releasing hormone in this process. Fourth, we will try to improve the methodology for conducting in situ hybridization analysis of GnRH mRNA in the brain. We believe this work will foster a better understanding of basic cellular neurobiology and help us to understand more about clinical problems related to human reproduction.

This grant covers experimental Elementary Particle Physics research by a group at Adelphi University in collaboration with other NSF and DOE supported scientists. The group will make precision measurements of the parameters which specify the electroweak interactions within the Standard Model of interacting quarks and leptons. They will initiate research on neutrino interactions at Fermilab and participate in design studies for the SSC.

The goal of this research is to understand the molecular physiology of the gonadotropin-releasing hormone (GnRH) and pro-opiomelanocortin neurons. An array of cells in the hypothalamus and forebrain secretes GnRH, which controls the release of pituitary gonadotropins and ultimately coordinates the reproductive axis in both male and female animals. Despite their acknowledged role in reproductive physiology, we understand little about the cell biology of these neurons. Our first objective is to examine the regulation of several important genes coexpressed by GnRH neurons in the rat brain. To this end, we will focus on two proGnRH processing enzymes, carboxypeptidase H (CPH) and alpha- amidating enzyme (PAM), and the neuropeptide galanin. We will test the hypothesis that these genes, as expressed in GnRH neurons, are targets for sex steroid-dependent feedback regulation. Using double in situ hybridization, we will measure and compare cellular levels of the messenger RNAs for CPH, PAM, and galanin in GnRH neurons under different steroid treatment regimens. Other neurotransmitter systems in the brain, including members of the endogenous opioid family (e.g., beta-endorphin from POMC), transduce hormonal signals from the gonads (e.g., testosterone and estradiol) and modulate the secretory activity of GnRH neurons. Our second objective is to learn more about the molecular physiology of testosterone-sensitive POMC neurons in the hypothalamus of the rat. We and others have previously shown that POMC neurons in the arcuate nucleus are functionally heterogeneous, but what molecular attributes determine this heterogeneity and how gene products, in addition to POMC itself, are regulated within these neurons are unknown. We will use double in situ hybridization to measure POMC mRNA and aromatase or estrogen mRNAs for the purpose of studying how these genes are regulated by sex steroids within anatomically defined subsets of POMC neurons. We believe this work will foster understanding of cellular neuroendocrinology and may offer clues to resolving clinical problems related to human reproduction.

During the past several decades, basic scientists and clinicians have contributed greatly to our understanding of fundamental aspects of reproductive biology. In turn, this understanding has been applied toward the development of improved methods of contraception and for the diagnosis and treatment of disorders of the reproductive system, including infertility, cancer, congenital anomalies, precocious puberty, and problems associated with menopause. Continued success in this area will be dependent upon training a new generation of scientists who know the basic principles of modern biology and are interested in applying basic research techniques on problems relevant to reproductive biology and medicine. This program is designed to provide a program of study and research apprenticeship toward the goal of preparing young scientists for a research career in the reproductive sciences. This program offers fellowships to 6 postdoctoral candidates with either a doctoral degree (Ph.D.) in a basic science or a professional degree (e.g., MD) in the medical sciences that seek training in reproductive biology. Training opportunities are available from 18 faculty mentors, representing 11 departments at the University of Washington, including the School of Medicine, the College of Arts and Sciences and the Fred Hutchinson Cancer Research Center. The disciplines represented include molecular and developmental biology, physiology and biophysics, reproductive neuroendocrinology, and clinical medicine. The continuation of this successful program will offer a unique and diverse training experience that will recruit new investigators into the field of reproductive biology at a time when there is intense public and scientific interest in the issues surrounding fertility control, hormone replacement therapy and the rule of reproductive hormones in cancer.

The goal of this research is to understand the molecular physiology of gonadotropin-releasing hormone (GnRH) and pro-opiomelanocortin (POMC) neurons involved in male reproduction. An array of cells in the hypothalamus and forebrain secretes GnRH, which coordinates the release of the pituitary gonadotropins and ultimately governs testicular function. Other neurotransmitter systems in the brain, including members of the endogenous opioid family (e.g., beta-endorphin, from POMC) and the excitatory amino acid glutamate, process hormonal signals (e.g., testosterone) from the testis which, in turn, modulate the secretory activity of GnRH cells. Our first objective is to learn how testosterone regulates the synthesis of gene products within the GnRH cell. Here, we will focus on the proGnRH processing enzymes [carboxypeptidase H (CPH) and alpha-amidating enzyme (PAM)] and the glutamate receptor (GluR-K1 type). Using double in situ hybridization, we will map the distribution of the genes coding for CPH, PAM, and GluR-K1 within anatomically defined subsets of GnRH neurons and examine their regulation by testosterone. If we find that testosterone influences the expression of one or more of these genes, we will proceed to test the hypothesis that the effect of testosterone on gonadotropin secretion can be attributed to changes in pro-GnRH processing or alterations in receptor-mediated sensitivity to glutamate. We will approach this by coupling the GnRH promoter to the structural gene for CPH, PAM or GluR-K1 and use these constructs to create and study transgenic mice expressing multiple copies of one of these chimeric genes within GnRH neurons. Our second objective is learn more about the molecular physiology of testosterone-sensitive POMC neurons in the hypothalamus. We and others have previously shown that POMC neurons in the arcuate nucleus are functionally heterogeneous, but what molecular characteristics determine this heterogeneity and how gene products, in addition to POMC itself, are regulated within these neurons are unknown. We will use double in situ hybridization to measure POMC mRNA and aromatase or estrogen receptor mRNAs for the purpose of the studying how these genes are regulated by steroids within anatomically defined subsets of POMC neurons. We believe this work will foster improved knowledge of cellular neuroendocrinology and may offer clues to understanding clinical problems related to human reproduction.

The goal of this project is to understand the mechanisms by which gonadotropin-releasing hormone (GnRH) stimulates the secretion of luteinizing hormone (LH). Recently, a new set of GnRH neurons have been described in embryonic primate brain. Using in situ hybridization, we confirmed the presence of GnRH mRNA-expressing neurons in the medial forebrain of adult pigtailed macaques (Macaca nemestina). These neurons appear to correspond to the neurons that control reproductive function. We also found many GnRH mRNA-expressing neurons in lateral forebrain areas. In rats, the neuropeptide galanin is coexpressed in a subset of GnRH neurons that control reproductive function, and this galanin may act to facilitate LH secretion. We found that galanin mRNA is expressed in a subset of the lateral GnRH mRNA-expressing neurons in pigtailed macaques. These results suggest that primates have GnRH mRNA-expressing neurons localized outside the medial forebrain, whose function is currently unknown, and that galanin may be a cotransmitter with GnRH in a subset of these neurons. We are also examining the effects of leptin on the reproductive axis in primates. In rodents, leptin regulates body weight and metabolism and appears to act as a metabolic signal to the reproductive axis. We found that leptin reverses fasting-induced suppression of LH in male rhesus macaques (Macaca mulatta), suggesting that leptin plays a similar role in primates. In addition, we have identified leptin receptor (Ob-R) mRNA-expressing cells in hypothalamic areas that control reproduction and feeding in monkeys and found that Ob-R mRNA is expressed in proopiomelanocortin and neuropeptide Y neurons but not in GnRH neurons. These results suggest that the effects of leptin on LH secretion may be mediated by neuropeptide Y and products of the proopiomelanocortin gene.

PI: Robert A. Steiner IBN: 9720143 Reproduction in mammals is governed by a hormonal communication system linking the brain and pituitary gland to the gonads. The brain is responsible for integrating hormonal signals (e.g., estrogen) from the ovaries and testes and directing the secretion of gonadotropin-releasing hormone (GnRH) from cells in the brain. These cells, in turn, serve as the final common pathway for the control of gonadotropin secretion from the pituitary gland. The overall goal of our research is to understand how these brain cells work to coordinate the functions of the reproductive system. The specific objective of this proposal is to learn more about the physiological significance of a small molecule, called galanin, and its receptor in the regulation of reproduction in the female rat. It has been shown by previous research that galanin plays a crucial role in the regulation of hormone secretion from the brain and pituitary; however, we have only a limited understanding of precise mechanisms by which galanin actually works. Galanin-containing cells are widely dispersed throughout the brain, including the forebrain and hindbrain, and galanin works together with other important signaling molecules (e.g., norepinephrine, NE, and GnRH) to exert its action. With probes that allow detection of messenger RNAs coding for galanin and its receptors coupled with a precise chemical analysis of the brain, experiments have been designed first, to identify the target cells for galanin's action in the brain; second, to reveal the functional significance of galanin produced in the hindbrain for the control of reproductive hormone secretion from the pituitary gland; and third, to learn more about the interactions of galanin and other important molecules in mice bearing genetically altered brain chemistry. The results of the studies outlined in this proposal should help us to understand more about the basic cellular and molecular mechanisms governing reproduction and other important physiologi cal functions in mammals.

human therapy evaluation; kidney transplantation; drug interactions; prednisone; diltiazem; chemotherapy; autologous transplantation; dosage; drug adverse effect; cytochrome P450; clinical research; human subject;

human therapy evaluation; emulsions; immunotherapy; dosage forms; kidney transplantation; cyclosporines; transplantation immunology; immunopharmacology; creatinine; clinical research; human subject;

The purpose of this study is to measure changes in ureagenesis after gene therapy in patients with OTC deficiency, an inborn error of urea synthesis. Current treatment is unsatisfactory. A Phase I study of adenoviral mediated gene therapy is underway. We are a collaborating insititution and wish to 1) perform heavy isotope/allopurinol studies to measure efficacy of the experimental treatment; and 2) to obtain blood for liver, renal, hematologic, and immune function to study safety.

To determine the distribution of GnRH mRNA-expressing neurons in pigtailed macaque brain and to examine whether subpopulations of GnRH neurons express galanin mRNA as they do in rats, we used in situ hybridization and computerized imaging. GnRH mRNA was expressed in the medial forebrain and GnRH mRNA-expressing neurons were found in lateral regions of the forebrain. These results suggest that galanin stimulates luteinizing hormone secretion in primates. In addition, they show that GnRH mRNA is widely expressed in the forebrain of pigtailed macaques and that, in some populations of neurons, galanin may act as a cotransmitter with GnRH. Using the same techniques, we mapped the distribution of leptin receptor mRNA. Leptin acts as a metabolic activator of the neuroendocrine reproductive axis in several rodent species, but whether it plays a similar role in primates is unknown. We observed leptin receptor mRNA in the anterior pituitary and several areas of the brain, sug gest ing that leptin is indeed a metabolic signal to the reproductive axis in primates. We have also begun to investigate whether the use of exogenous estrogen or of selective estrogen receptor modulators affects neuropeptide gene expression. We are now testing whether estrogen receptors are coexpressed on neurons in the hypothalamus that may mediate changes in GnRH pulsatility. FUNDING NIH grants RR00166 and HD12629. Finn, P.D., Cunningham, M.J., Pau, K.Y., Spies, H.G., Clifton, D.K., and Steiner, R.A. The stimulatory effect of leptin on the neuroendocrine reproductive axis of the monkey. Endocrinology 139:4652-4662, 1998.

Molecular compounds in the brain called neuropeptides often regulate physiological functions, acting similarly to hormones. A new member of the family of neuropeptides known as galanins recently has been isolated in mammals and called galanin-like peptide (GALP). Preliminary evidence suggests that GALP plays a role in the neuroendocrine regulation of pituitary functions, but little is yet known about the functions of this compound. This project uses neuroanatomical, physiological and molecular biological techniques to reveal the anatomical circuitry of the cells containing GALP, to discover how and where the expression of GALP occurs, and to develop a mutant mouse model with a targeted deletion of the GALP gene to reveal physiological functions. Results of these studies should provide a novel understanding of possible roles for this molecule in physiological processes such as regulation of metabolism, body weight, reproduction, lactation and growth.
This exploratory project has both high risk and high potential impact. It remains unknown what the specific discoveries will be, but novel data are likely to have major importance, extending beyond neuroendocrinology to regulatory physiology and developmental biology. Graduate and postdoctoral training will also be done in a laboratory with a long record of excellence.

[unreadable] DESCRIPTION (provided by applicant): Galanin-like peptide (GALP) is a newly discovered member of the galanin family of neuropeptides. GALP shares a partial sequence homology with galanin; however, GALP is coded by a separate gene and is likely to have its own unique receptor. Work from our laboratory and others has shown that the expression of GALP mRNA in the brain is limited to a cluster of neurons in the hypothalamic arcuate nucleus and the median eminence. We have recently discovered that GALP neurons are direct targets for the adipocyte-derived hormone leptin. The expression of GALP mRNA is reduced in leptin-deficient states, which can be reversed by the concomitant administration of leptin. When administered into the brain, GALP produces a dose-dependent inhibition of feeding and body weight and also stimulates luteinizing hormone (LH) and testosterone secretion. These studies suggest that GALP neurons serve as part of the hypothalamic circuitry linking the regulation of body weight and reproduction; however, beyond these observations, we understand little about GALP's physiological importance. We propose to use neuroanatomical, pharmacological, and molecular biological techniques to reveal the anatomical circuitry governing GALP cells, map their projections, and discern GALP's functional significance. Our primary aims are 1) to examine the effects of leptin, insulin and ghrelin on GALP neurons and characterize the synaptic inputs and molecular physiology of these cells-focusing on inputs from NPY, proopiomelanocortin, and serotonin, as well as on key transcription factors; 2) to identify the targets of GALP projections in the brain and to reveal its signaling mechanisms; and 3) to assess the functional significance of GALP by evaluating mice with a targeted deletion of the GALP gene, examining the role of GALP in mediating the effects of leptin on the neuroendocrine reproductive axis, and evaluating the functional significance of NPY inputs to GALP neurons, particularly in the context of gonadotropin secretion. Learning the basic circuitry that couples GALP to other neuronal systems, understanding more about the molecular physiology of GALP neurons, establishing the cellular, molecular, and physiological effects of GALP, and learning how GALP neurons are regulated by metabolic hormones are fundamental to understanding GALP's functional role in the orchestration of the neuroendocrine reproductive system, as well as other important physiological processes. [unreadable] [unreadable]

transplant rejection; transplantation immunology; human therapy evaluation; postoperative state; statistics /biometry; hormone metabolism; pharmacokinetics; drug metabolism; cyclosporines; sirolimus; outpatient care; prognosis; postoperative complications; prednisone; circadian rhythms; clinical research; human subject;

DESCRIPTION (provided by applicant): The KiSS-1 gene codes for a family of peptides called kisspeptins, which bind to a G protein-coupled receptor known as GPR54. KiSS-1 and GPR54 are expressed in the forebrain, and mutations in the GPR54 gene cause hypogonadotropic hypogonadism in humans and mice. Kisspeptins stimulate gonadotropin- releasing hormone (GnRH) and gonadotropin (LH and FSH) secretion, and the KiSS-1 gene is regulated by gonadal steroids-suggesting that kisspeptin signaling through GPR54 plays a role in the neuroendocrine regulation of reproduction. The overall goal of this research is to understand the physiological function of kisspeptins in the regulation of gonadotropin secretion in the female rat and mouse. Our first objective is to assess the role of kisspeptins in the preovulatory gonadotropin surge. Here, we will test whether kisspeptin/ GPR54 mRNA signaling pathway is critical for the generation an estrogen (E)/progesterone (P)-induced LH surge. We will also evaluate the possibility that KiSS-1 neurons of the anteroventral periventricular nucleus (AVPV) mediate the effects of E, P, and circadian signals from the suprachiasmatic nucleus (SCN) on the generation of LH surges. The second objective is to investigate the role of kisspeptins in the onset of puberty and sexual differentiation of the LH surge mechanism. In these experiments, we will evaluate changes in kisspeptin neurons over sexual development and determine whether these changes are dependent on sex steroids. We will also investigate whether puberty is associated with an increase in the ability of kisspeptins to stimulate the activity of GnRH neurons. In addition, we will determine whether kisspeptin/GPR54 signaling in GnRH neurons plays a critical role in puberty by evaluating the effects of introducing a functional GPR54 gene into GnRH neurons of GPR54 KOs. Finally, we will investigate whether sex differences in the expression of KiSS-1 and GPR54 are attributable to organizational processes that during the neonatal critical period or hormone-dependent activational events at puberty. Elucidating the role of kisspeptins in the development and regulation of gonadotropin secretion in females may improve our understanding of idiopathic hypogonadotropic hypogonadism in humans and could provide the scientific rationale for improved therapies to treat precocious or delayed puberty and infertility. It's also conceivable that this knowledge could serve as the basis for the development of new and better strategies for hormonal contraception.

DESCRIPTION (provided by applicant): Ovulation is triggered by neural circuits in the brain, which senses a rising tide of estradiol (E2) and-at the right time-generate a surge of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH), causing ovulation. However, the cellular and molecular pathways in the brain that orchestrate this phenomenon are only partially understood. In rodent species, the anteroventral periventricular nucleus (AVPV) comprises part of the circuitry necessary to produce the GnRH/LH surge; however, until recently, the phenotype of the neurons within the AVPV that serve this function were a mystery. Within the past 3 years, it has become widely accepted that a product of the Kiss1 gene, kisspeptin, provides an important-perhaps essential-signal to GnRH neurons. The overall goal of this proposal is to identify the role that Kiss1 neurons in the AVPV play in the generation of the GnRH/LH surge and to reveal the neural, hormonal, and molecular pathways involved in that process. The first specific aim is to determine whether Kiss1 neurons in the AVPV and kispeptin produced by those particular neurons are essential for generating the GnRH/LH surge and to delineate the biophysical properties of those neurons as a function of the surge. Progesterone receptor (PR) signaling is an essential component of the surge mechanism, but the cellular and molecular basis of PR's action in the brain as it relates to the surge is not known. The second specific aim is designed to determine the functional significance of PR in Kiss1 neurons of the AVPV. The third specific aim is to identify the neural afferents and signaling pathways that control Kiss1 neurons in the AVPV and to evaluate their physiological significance in the context of GnRH/LH secretion. The experimental approach combines more traditional methodologies, such as in situ hybridization, immunohistochemistry, and hormone manipulations and measurements, together with innovative gene-targeting strategies. These include methods to 1) identify Kiss1 neurons with GFP and tdTomato for recording in slice preparations; 2) ablate specific neurons through the use of selective diphtheria toxin receptor expression; 3) map the afferent inputs to Kiss1 neurons with retrograde tracing by introducing a fluorescent-tagged pseudorabies virus into Kiss1 neurons; 4) knock-down and knock-in specific genes in Kiss1 neurons with the use of a lentivirus delivery system; and 5) fingerprint the transcriptome of Kiss1 neurons by harvesting individual cells and employing a new ribotagging methodology. The studies described in this proposal utilize a multi-disciplinary approach to advance our understanding of a critical element in the female reproductive life cycle-the neuroendocrine mechanism that governs ovulation.

The Polar Learning And Responding (PoLAR) Climate Change Partnership is using fascination with the changing polar regions and novel educational approaches to engage adult learners and inform public understanding and response to climate change. Learning research and activities implemented during the Phase I demonstration project show that games and game-like approaches motivate exploration and learning of complex material. Focus has been placed on the poles because climate change is rapid in these regions and has global consequences. Images of the changing Arctic and Antarctic have become emblematic of environmental change for the public at large.

PoLAR partners include expertise in: 1) Climate Science, both in Natural Science and Social Science; 2) Learning and Decision Science, including Learning Theory and Practice and Decision Science; and 3) Practitioners in Formal education, Informal education, and Gaming. The intellectual merit of the PoLAR Partnership is the combination of learning, decision, and climate science applied to educational approaches for adult learners. Adults, be they community leaders, the general public, pre- and in-service teachers, or college students, are today's decision-makers. Informed decisions are more likely if individuals are aware of the scientific evidence of climate change and potential economic and social consequences. Research is being conducted in this Phase II project to evaluate the impact of different platforms and tools in raising awareness and improving understanding. The project seeks to: 1) Deepen adult learner awareness and understanding of climate change; 2) Inform responses to climate change impacts through engaged problem-solving; and 3) Advance knowledge on more effective modes of climate change education and outreach.

This project will transform education policies and practices by catalyzing new ways of learning about climate change at the poles based on scientific evidence, learning theory, and education practice, including current and emerging technology. Activities to achieve this goal include: 1) Providing transformative educational approaches that are easy to disseminate and exciting to use in homes, museums, classrooms, and communities; and 2) Inspiring change in practices and policies by seeding game-like approaches in informal and formal educational environments in collaboration with catalytic associates.

This Phase II CCEP project is serving as a hub of communication and dissemination of information on polar climate change through the Polar Home website, which leverages existing resources, including the Climate Change Education Program Alliance (CCEPA). Diverse communities are being engaged through professional development of and public outreach to key stakeholder communities: AMNH teachers, Alaskan leaders through culturally responsive camps, and radio dispatches in multiple languages. The project has the potential to reach millions of adults through partners and associates including the Alaskan Association of Interior Native Educators, Games for Change, Isla Earth, Arctic Portal, AMNH, Association of Arctic Expedition Cruise Operators, American Geophysical Union and WWF Global Arctic Programme.

This project is one of six Phase II projects being funded through the Climate Change Education Partnership (CCEP) program. The CCEP program was developed as part of the NSF Climate Change Education program, established through Congressional appropriations in FY 2009. The CCEP program is a one-time, dedicated NSF effort to establish a coordinated national network of regionally- or thematically-based partnerships devoted to increasing the adoption of effective, high quality educational programs and resources related to the science of climate change and its impacts. The CCEP portfolio encompasses a major interdisciplinary research and development effort designed to promote deeper understanding of, and engagement with, climate system science and the impacts of climate change on natural and human systems. The vision of this program is a scientifically literate society that can effectively weigh the evidence regarding global climate change as it confronts the challenges ahead, while preparing the innovative scientific and technical workforce to advance our knowledge of human-climate interactions and develop approaches for a sustainable, prosperous future. Each CCEP is required to incorporate innovative collaborations among expertise of climate scientists, learning scientists, and education practitioners in either formal or informal learning environments to research, design, and test new models and strategies for effective teaching and learning about climate science. With its focus on interdisciplinary approaches and transformative scales of impact, the CCEP program occupies a unique and complementary niche in the portfolio of Federal investments related to climate science education and workforce development.