Rochelle D. Schwartz-Bloom - US grants

The overall objective is to determine the mechanisms of regulation of the GABA receptor/chloride (C1-) ion channel complex in rat brain. Since abnormal GABAergic neurotransmission appears to be a major factor in seizure disorders, regulation of the 'transducer' component (the GABA receptor/C1- ion channel) of GABA-ergic transmission may play an important role in the etiology and response to seizure activity. Two major biochemical tools will be used to achieve these objectives. One involves studies of the regulation of GABA receptor-gated C1- ion channel binding sites labeled with (35S)TBPS. The other involves studies of the regulation of GABA receptor-mediated 36C1- ion flux. An important feature of these techniques is that they can be used in the same tissue from the same animals under identical conditions, something that was not possible in the past. The research plan is divided into 3 parts. The first is to determine the cellular mechanisms of regulation in vitro. Alterations in GABA receptor/C1- ion channel activity will be measured subsequent to 1) desensitizing conditions 2) alterations in membrane phospholipids by phospholipases (i.e., release of free fatty acids and subsequent formation of oxygen radicals and lipid peroxides) and 3) exposure to phosphorylating conditions. The role of these cellular processes in regulating the GABA receptor complex in vivo will be determined in the second and third parts of the research plan. In the second part, alterations in the sensitivity of the GABA receptor/C1- ion channel will be studied following repeated exposure of rats to agonists off the GABA receptor complex which are known to down-regulate GABA recognition sites. These drugs which act at 3 distinct sites on the GABA receptor complex include GABA agonists, benzodiazepines and barbiturates. Each of these drugs has anticonvulsant activity. In the third part studies are designed to measure changes in GABA receptor/C1- ion channel activity following both chemically- and electrically-induced seizures. Convulsants which act at distinct sites on the GABA receptor complex (bicuculline and picrotoxin) and maximal electroshock will be administered repeatedly over a 10 day period. The studies will provide new insights into the mechanisms that regulate GABAergic neurotransmission on a cellular level. This research should reveal the importance of these mechanisms in the actions of convulsant and anticonvulsant drugs and in the physiology of seizure activity itself.

In cases of cardiac arrest or stroke, the brain is deprived of blood, glucose, and oxygen and ischemic damage to specific neuronal populations occurs. One of the major factors that contributes to the ischemic damage is an increased excitability of neurons. Since neuronal excitation can be inhibited by the neurotransmitter, gamma-aminobutyric acid (GABA), the objective of this research plan is to determine the role of GABA neurotransmission in the neuronal damage following transient global ischemia. The model involves occlusion of 4 vessels (cerebral and carotid arteries) in the rat; changes in GABA neurotransmission are determined at both pre and postsynaptic loci. For presynaptic studies, in vivo microdialysis will be used to measure extracellular GABA levels in brain regions selectively vulnerable to ischemic damage. For postsynaptic studies, MRNA expression of GABA/A receptor subunits, GABA/A receptor binding, and function will be assayed using 1) in situ hybridization histochemistry, 2) receptor autoradiography (using [3H]muscimol to label GABA/A agonist sites and [35S]t- butylbicyclophosphorothionate to label the GABA-gated chloride channel, and 3) ion flux techniques to measure GABA gated 36 chloride uptake in synaptoneurosomes from cerebral cortex, hippocampus, and striatum. The research plan is divided into 3 parts to determine: 1) if changes in extracellular GABA levels promote or prevent ischemia-induced neuronal degeneration, 2) if changes in GABA/A receptor expression, binding, and function in selectively vulnerable regions promote or result from ischemia-induced neuronal death, and 3) if pharmacological agents that enhance GABA/A receptor function protect vulnerable neurons from degeneration and preserve GABA/A receptor characteristics and function in rats with transient global ischemia. These studies should provide new insights into the role of GABA neurotransmission in the initiation, promotion, or prevention of ischemic-induced neuronal injury. In addition, these studies may provide the bases for investigating new treatment strategies for dementias and sensorimotor deficits that occur after cardiac arrest and stroke.

DESCRIPTION: (Applicant's Abstract) The overall objective of this program is to help high school students integrate what they have learned in biology and chemistry using pharmacology, the study of drug action. A partnership between a scientist/educator and a high school chemistry teacher will lead this effort. A series of modules (units) will be developed for high school teachers to teach and reinforce several basic biology and chemistry concepts using the science of drug use and abuse as a relevant context. The National Science Education Standards will be used as the framework for developing units to be integrated into existing science education curricula. The final materials will be published in a multimedia format so that teachers can access 3D graphics. The primary goal of the proposed program is to enhance science (biology and chemistry) knowledge of high school students. Secondary goals are: 1) provide science teachers with tools to integrate principles of biology and chemistry, 2) to engage teachers in the development, field-testing and evaluation of instructional materials, 3) to increase interactions between high school teachers and basic scientists, and 4) to introduce students to careers in science that involve research on the actions of drugs and drug abuse. Specific activities will be carried out during the funding period to achieve the stated goals and objectives: 1) development of a teachers' manual containing a set of 10 units that use principles of biology and chemistry to describe the actions of drugs in the body; 2) a national recruitment of 48 high school biology and chemistry teachers to participate in the field-testing of the materials; 3) summer workshops for the teachers (the test group and the "wait-list" control group) to participate in the manual development, to obtain science content background and to work with scientists to design supplemental activities; 4) field-test of the materials by the teachers in their biology and chemistry classes; 5) evaluation of the teachers' experience and students outcomes using questionnaires and a testing protocol developed to measure differences between the test and "wait-list" control groups and between the "wait-list" group before and after use of the units; and 6) the publication and dissemination of materials nationwide with the help of the National Science Teachers Association. The application of biology and chemistry to drug use should stimulate thinking about the role of these sciences in "every day life" and help students understand how drugs actually work and affect their bodies.

DESCRIPTION: (Verbatim from the Applicant's Abstract) Transient cerebral ischemia, produced by cardiac arrest, cardiopulmonary bypass surgery, etc., causes neuronal death in selectively vulnerable regions of the brain such as area CA1 of the hippocampus. There exists considerable evidence that glutamate neurotransmission plays an important role in ischemia-induced neuronal death. In contrast, relatively little is known about the role of GABA neurotransmission. The long-term objectives of this research program are to understand the role of GABA neurotransmission in ischemia-induced neuronal death; the major working hypothesis is as follows: GABA neurotransmission is reduced early after ischemia and this may be due, in part, to the generation of reactive oxygen species. The decrease in GABA neurotransmission may promote proapoptotic and other injury signals that eventually lead to neuronal death. Pharmacologic enhancement of GABA neurotransmission early after ischemia may prevent the loss of GABA neurotransmission and generation of early signals of neuronal injury. Both in vivo and in vitro models of ischemia will be used for these studies, in combination of the acutely prepared hippocampal slice. The Specific Aims of the research are to: l) determine the effect of transient cerebral ischemia (in vivo) on GABA neurotransmission within the hippocampal slice, 2) determine the role of oxidative stress in ischemia-induced changes in GABAA responses in the hippocampal slice, 3) determine the potential mechanisms by which oxidative stress (i.e. H2O2) affects GABAA responses in the hippocampal slice and 4) determine the effect of increasing GABA neurotransmission on early injury signals following ischemia in vivo and in vitro. GABAA responses will be measured in differentially-vulnerable areas of the hippocampus including CAl pyramidal neurons, CA1' interneurons and CA4 interneurons using a Cl- sensitive fluorescent dye, MEQ, and W laser scanning confocal microscopy. Perforated patch recordings of area CA 1 pyramidal neurons will provide additional information about changes in the Cl- gradient. Early markers of cell injury will be assessed along with the measurement of GAB4A responses. These markers provide biochemical, structural and functional information concerning neuronal viability. They include, c-fos and MAP2 expression, the proapoptotic signals, cytochrome c efflux and caspase-3 activation, and ATP levels. Understanding how ischemic insults affect inhibitory neuronal transmission and how specific populations of neurons die will help us to identify new treatment strategies to prevent ischemia-induced neuronal death in humans.

DESCRIPTION: During the past 4 years, we have carried out a very successful science education partnership (funded by NIDA) between a scientist/educator (the Principal Investigator) and a high school chemistry teacher (Dr. Myra Halpin). The overall objective of our partnership was to help high school students learn biology and chemistry better by presenting basic concepts within the context of pharmacology (e.g. drug abuse). The results of the teacher and student testing were outstanding, leading us to continue our partnership to make our program even better. Here we present a new research plan, modified according to our past experience, to produce and deliver our instructional program to high school biology and chemistry students using current technologies. We will develop additional instructional modules for high school teachers to reinforce basic biology and chemistry concepts using the science of drug use and abuse as a relevant context. Specifically, we have the following objectives: 1) Develop an instructional program consisting of 10 modules that use principles of biology and chemistry to describe the actions of drugs in the body. 2) Build an interactive website for teachers and students to access the pharmacology modules during the field-testing. 3) Recruit - 300 high school biology and chemistry teachers nationwide to field-test the modules. Teachers will be randomized to an experimental group and a "wait-listed" control group. 4) Conduct 2 types of teacher training workshops; a 6-hour on-site workshop at the annual NSTA and NCSTA meetings and a 6-hour two-way video workshop with simultaneous broadcast between the NC School of Science and Math (NCSSM) and selected school districts throughout the US. In the workshops, high school biology and chemistry teachers will obtain background for the science content and work with scientists to design supplemental activities. 5) Field-test the modules. After participating in the workshops, teachers use the modules in biology and chemistry classes at their high schools. 6) Determine the program?s outcomes by evaluating the teachers? and students? experiences. Students in the wait-listed control group and the experimental groups will be given end-of-course tests containing questions of basic biology and chemistry knowledge, as well as advanced knowledge about drugs. Teachers will be tested on pharmacology knowledge before and after the workshop, and again 1 year later. 7) Make final revisions for the publication and dissemination of the modules on the interactive website and the CDROM. The application of biology and chemistry to drug use should stimulate thinking about the importance of these sciences in "every day life" and help students understand how drugs actually work and affect their bodies. Based on our previous study, the students learn science better too!

Currently, US high school students rank low in science and math compared to their peers in other nations. The Alcohol Pharmacology Education Partnership (A-PEP) is designed to help high school students learn biology, chemistry, and math better by presenting basic concepts within the context of alcohol pharmacology. The basis for pursuing this project results from outstanding effectiveness of our previous program that focuses on drugs of abuse. Here we present a research plan to produce and deliver a new instructional program to high school biology and chemistry students using high quality materials (hard copy and web-based) and current distance learning technologies. We will develop instructional modules for high school teachers to reinforce basic biology, chemistry, and math concepts using the science of alcohol use and abuse as a relevant context. The specific objectives are: 1) Develop a series of 6 modules that use principles of biology, chemistry, and math to describe the actions of alcohol in the body. 2) Build an interactive website for teachers and students to access the alcohol pharmacology modules during the fieldtesting. 3) Recruit approximately 300 high school biology and chemistry teachers nationwide to field-test the modules (teachers serve as their own controls). 4) Conduct 2 types of teacher training workshops; a 6-hour on-site workshop at the annual NSTA and NCSTA meetings and a 6-hour two-way video workshop with simultaneous broadcast between the NC School of Science and Math (NCSSM) and school districts throughout the US. In the workshops, high school biology and chemistry teachers will obtain background for the science content and work with scientists to design supplemental activities. 5) Field-test the modules. After participating in the workshops, teachers use the modules in biology and chemistry classes. 6) Determine the program's outcomes. Students (in control and experimental groups) will be given end-of-course tests containing questions of basic biology and chemistry knowledge, as well as advanced knowledge about alcohol pharmacology. About 15,000 students will be tested; analysis will use hierarchichal linear modeling. Teachers will be tested on pharmacology knowledge before and after the workshop, and again 1 year later. 7) Publish results and release the curriculum on the A-PEP website. The application of biology, chemistry, and math to alcohol use should stimulate thinking about the importance of these sciences in "every day life" and help students understand how alcohol actually works and affects their bodies. Based on our previous study, the students learn science better too.

The Robert Noyce Scholarship Program at Duke University provides funding to train eleven secondary science and mathematics teachers per year over a three-year period for a total of 33 students completing the master's degree in teaching. The recruitment of under-represented minorities and undergraduates who might not consider teaching is emphasized. The Program is increasing the number of highly trained mathematics and science teachers who have advanced study in their teaching discipline and extended teaching experience under the direction of highly skilled mentors. By training in the Durham Public Schools, a high-need school system, these teachers are well prepared to begin their careers in similar school systems where the need for qualified mathematics and science teachers is greatest. Students complete five graduate level courses in their teaching field in addition to course work in education. The teaching internship takes place under the direction of a career teacher who has received extensive training in mentoring and adult development. The internship covers one full semester and a portion of the second semester so that all participating students gain extensive experience teaching high school students in a variety of disciplinary courses and at various performance levels. Each teaching intern works with high school students who are not fluent in English and with students who have been identified with special learning needs in addition to high performing students in advanced placement classes.

DESCRIPTION (provided by applicant): Science literacy in the US adolescent population ranks low compared to other developed nations and is declining (National Center for Education Statistics). A consequence of this deficiency has been that students do not have the tools to make informed decisions about issues concerning their health. One area in which students may lack the scientific tools to make healthy choices is in the use of tobacco products. In particular, the tobacco industry may be able to take advantage of our students'lack of scientific literacy, especially with their creative marketing of so-called "safer" tobacco products (i.e., light/ultralight cigarettes, reduced-exposure products, "natural" cigarettes, and smokeless tobacco). Research suggests that adolescents who don't smoke may be lured into using these products because of the "safer" implication, or they may delay quitting smoking thinking a safer alternative will be available later on. Currently, the main forum for teaching students about tobacco, smoking, and addiction is the high school health education course. Yet, health education courses do not typically provide a level of scientific understanding of these important topics. Moreover, teachers of these courses are usually physical education teachers, who do not have the background to teach the science about tobacco and nicotine addiction. Thus, we propose a partnership between university scientists and high school teachers to help teachers bring science into their health education course. Our overall goals of the project are to 1) increase science literacy of adolescents on the topic of tobacco use and nicotine addiction, 2) provide students with tools to resist the creative marketing of alternative tobacco products, and 3) help students make appropriate decisions about (not) smoking or using other tobacco products that carry implied claims of being "safer" than regular cigarettes. To achieve these goals, we have 5 specific aims: 1) Develop a science education- based module on tobacco products and nicotine addiction for the high school health education course;2) Provide professional development to health education teachers to help them serve as learning facilitators of the science education module;3) Field-test the science education module in high school health courses using a randomized, controlled design;4) Perform a multi-modal evaluation of the effect of the science education module on several outcomes including, science content knowledge about addiction and cancer, students'risk perception of addiction and cancer, ability to resist marketing of safer tobacco products, susceptibility to smoke/use tobacco products, and self-reported use;5) Disseminate the program nationally. We propose that our approach may serve as a model for using science education to inoculate teens against the constant barrage of information about legal and illegal substances that cause disease, including addiction. This is especially appropriate for the high school health education course. Public Health Relevance: This project brings science education to the Health Education class in high schools. We propose that our approach may serve as a model for using science education to inoculate teens against the constant barrage of information about legal and illegal substances that cause disease, including addiction.

As we move ahead into the genomic era, the public must grasp the importance of the impact of exposure to toxins such as environmental tobacco smoke (ETS) on the health of their children. Thus, we propose to translate the findings of our Center Investigators using a social-media approach that engages the community stakeholders in developing the communication materials. Our goals are 1) to translate what scientists learn in their research to easily understood information for the public and 2) to increase science literacy of the public on the topic of epigenetics with respect to ETS and disorders such as Attention-Deficit / Hyperactivity Disorder (ADHD). Ultimately, the goal of our science education approach is to help the public make appropriate decisions to abstain from smoking tobacco products and to avoid exposure to others who smoke. To achieve these goals, we have 6 specific aims: 1) Develop a simple science primer that uses lay language to communicate the effects of ETS on one's genes and how these effects can be handed down to one's offspring. Various stakeholders (e.g., doctors, pregnant patients, teens) will participate in the science primer development; 2) Disseminate the science primer in community health centers to stakeholders along with a call for contest applications; 3) Develop a working document that translates the major findings of each of the 3 Center projects into lay language (add to the science primer in a section called newest research); 4) Hold a contest in which stakeholders construct their own YouTube videos that convey any of the NICHES findings. A committee of judges will choose a set of winning videos for a small field test and eventual dissemination; 5) Conduct a field-test in community health centers using the winning YouTube videos to determine the stakeholders' attitudes and knowledge about the effects of ETS on themselves and their children; 6) Work with NIEHS to disseminate the YouTube videos and science primers on their website; post links to these materials online from the NICHES website and our science education website (www.rise.duke.edu).

The Duke University Master of Arts in Teaching (MAT) Program, in collaboration with the Durham Public Schools and the STEM departments in the Trinity College of Arts and Sciences, establishes a Robert Noyce Scholarship Program Phase II Project to provide stipends to 30 Duke Noyce Scholars during the project period. This project has four goals: 1) Recruit and enroll diverse cohorts of highly-qualified STEM graduates and mid-career professionals; 2) Prepare teachers to improve student achievement in mathematics and the sciences; 3) Support new teachers during the first three years of their career as they teach in high-need school districts; and 4) Continue longitudinal evaluation and analysis of the project to determine those factors most effective in recruiting, preparing, and retaining highly-qualified teachers for high-need school districts.

This project extends and expands work completed in a Phase I project awarded in 2006. In particular it seeks to increase teacher retention and to attract more underrepresented minority STEM majors and professionals into STEM teaching. A comprehensive set of activities is implemented to reach these goals. This Noyce project seeks to build relationships with and recruit from prestigious historically black colleges and universities (HBCUs). The one-year MAT Program for Noyce Scholars includes a curriculum of pedagogical coursework, graduate coursework in the Mathematics and Science disciplines, and two-semester internships in high schools of Durham Public Schools. New teachers in their first three years in the profession are supported by an innovative, structured teacher mentoring program that includes the early-career Duke Noyce graduates, experienced Duke Noyce graduates, and faculty. Other support activities include bi-annual Noyce Learning Conference events and support of professional development through conference participation.

The broader impacts of this project include increasing the diversity of highly-qualified science and mathematics teachers and implementing a model to effectively recruit, prepare and retain STEM teachers. The systematic mentoring program for early-career teachers encourages higher teacher retention rates and provides a model that can be adapted at other programs. Through the evaluation activities, this project advances the understanding of strategies to develop and implement an effective MAT program for STEM majors and mid-career professionals and to support new teachers in high-need school districts.

DESCRIPTION (provided by applicant): The 2012 National Science Education Standards published by the National Research Council call for an integrative, research-based curriculum in science that incorporates high quality laboratory activities that help students learn to investigate, to construct scientific assertions, and to justify those assertions. Yet in their own U.S. Lab Report, the NRC indicates that the majority of high school students participate in science laboratory experiences that are poorly developed and lack clear learning goals. Currently, lab activities are inhibited by many factors, including limited funds and resources, large class sizes, and inadequate teacher training. Moreover, high school science labs are often boring, and use the cookbook approach. Over the past 15 years we have developed and assessed the efficacy of substance abuse-focused modules on learning in high school biology and chemistry. Topics about drugs and alcohol are highly relevant and interesting to high school students. In our most recent study, we developed a lab activity that engages students virtually (www.rise.duke.edu/SEEK). The widespread use of this resource by teachers in our study led to the development of this proposal. We will develop a web-based platform (REX) for educators and their students to engage in virtual laboratory experiments performed by real scientists. Our overall goals of this project are to 1) provide teachers with a rich resource that can be used to integrate inquiry-based virtual lab experiences into the classroom , 2) increase high school student mastery of basic biology and chemistry principles and 3) increase student interest in science and science careers (especially in areas of substance abuse). To achieve these goals, we have 4 specific aims: 1) develop REX (Real Experiments), an interactive web-based platform, to conduct lab experiments online that real scientists perform in areas of substance abuse, 2) design 6 pharmacology-oriented experiments focused in areas of drug and alcohol abuse to populate REX. We will incorporate an interactive algorithm that allows students to participate in the design of their own experiment, analyze data generated by real scientists, interpret results, and reflect on their findings and next steps, 3) field-test REX in10 high school science classrooms (~ 1000 students) in the Durham, NC school district, which comprises a large population of underrepresented minorities, and 4) perform several types of assessments that test the effect of REX on mastery of basic biology and chemistry principles and determine the effect of REX on interest in science and science careers (the study will be controlled). Finally we will conduct an evaluation of the usability of REX by teachers before dissemination publically. We expect that our engaging online resource will be especially useful to teachers and schools without money, training, or infrastructure to conduct laboratory experiments.