Bruce Johnson - US grants

This award provides funds to the Department of Neurobiology and Behavior at Cornell University to help purchase equipment which will be used to teach undergraduate biology students, and students in allied fields such as physics, engineering and computer sciences, modern techniques in cellular neuroscience through hands- on laboratory experience. This will be accomplished by active research scientists in a series of three undergraduate courses entitled: 1) Principles of Neurophysiology, 2) Electronics for Neurobiologists, and 3) Computer Interfacing for Neurobiologists. In the first course, undergraduates will use the state-of-the-art research equipment (computers, voltage clamp amplifiers, micromanipulators, microelectrode pullers, and perfusion pumps) in laboratory exercises designed to teach the principles of electrical signalling in the nervous system. In these exercises, computer data acquisition and analysis and teaching students the use of Macintosh II computers, along with the related hardware and software necessary for this purpose will be emphasized. This course will replace all standard vertebrate preparations with invertebrate model systems. In the electronics course, students will learn fundamental principles of electronics as applied to electrophysiology and other biological fields to design simple, relevant circuits such as those used for basic voltage and patch clamp amplifiers. The computer interfacing course will use the Macintosh II computers to teach the technical details (hardware and software) of computer interfacing methods in biological experiments. This project has important significance not only in providing undergraduates with training in new and powerful methods of experimental neuroscience, but also in developing advanced teaching tools useful for other neuroscience training programs. Through this project, undergraduate students will gain theoretical and technical skills that will help them be productive scientists in both corporate and academic research environments. The grantee is matching this award with non-Federal sources.

The research plan explores fundamental questions related to the role of nitric oxide (NO) in cytokine-induced lung injury. Derangements in pulmonary vasomotor and endothelial function are prominent in this pathophysiology. Many of these sequelae are reproduced by the inflammatory cytokines which in turn influence the production of NO by constitutive (cNOS) and inducible (iNOS) nitric oxide synthases. The role of these isoforms, however, is not clear. Nonspecific inhibition of the enzymes has yielded both beneficial and injurious results. Our overall hypothesis is that transient cytotoxic NO production by iNOS mediates cellular dysfunction and damage while continued physiologic production of NO by cNOS maintains homeostasis and is protective during cytokine induced lung injury. We first evaluate cultures of pulmonary arterial microvascular smooth muscle and endothelial cells where cytokine stimulated NO synthase expression and associated cytotoxicity are defined. We then selectively alter NO production by the different isoforms and evaluate the resulting cytotoxicity and cellular dysfunction. Specifically, we inhibit iNOS in cytokine exposed cultures with aminoguanidine and anti sense oligonucleotides, and we simulate iNOS induction in cultures without cytokines by iNOS transfection and the addition of the NO donor S-nitroso-N-acetylpencillamine. In parallel, we inhibit cNOS in cytokine exposed cultures with antisense oligonucleotides and L-N(omega)-nitroarginine, and we stimulate cNOS activity by transfection.

*** Smith The Research Experiences for Undergraduates site at the Rice Quantum Institute of Rice University will be continued. The main objective of the program is to provide undergraduate students with an opportunity to observe and participate in research in a highly-interdisciplinary university research environment with strong faculty support. The program has, and will continue to focus on active participation in research, but also strives to show the participants how the research funding process works, give them insight into applications of basic research, and provide them with an understanding of the fundamental motivations for research activity. Each undergraduate becomes affiliated with one of the 25 research groups at the Quantum Institute, and works on an independent project that he/she can bring to completion in the allotted ten-week time frame. In addition to research activities, a special seminar series for the participants is organized in which invited speakers deal with topics ranging from "hot" topics in research, commercial applications of basic research, entrepreneurship, graduate schools, opportunities for employment, and other topics. ***

Abstract

The objective of this research is the development of a new type of a scanning local probe microscope capable of obtaining chemical information with nanoscale resolution and to utilize this microscope in a wide range of applications pursued by different research groups at Rice University. The microscope will consist of a metallodielectric nanoparticle mounted or integrated as an Atomic Force Microscope tip (AFM) tip. The nanoparticle will be designed to have plasmon resonant response in the infrared region of the spectrum (2.7 -10 microns in wavelength; 1000-3600 cm-1). The strong electromagnetic field enhancements associated with the excitations of plasmons in the probe tip will dramatically enhance the cross sections for infrared excitation of dipole active vibrational modes in the tip-sample junction

This project will result in a new and unique nanoscale spectroscopic tool that will be useful across a very broad range of technical applications, such as fundamental nanoscale studies in the physical and chemical sciences, a valuable new imaging probe in the life sciences, and a unique, breakthrough sensor technology for environmental analysis and detection of trace chemical species. The highly collaborative multidisciplinary instrument development team consists of researchers in the departments of Electrical and Computer Engineering, Chemistry, Physics, and Bioengineering. Two courses will be developed during this project addressing the theoretical and experimental aspects of nanoscale instrument component design and fabrication. A large number of users for this instrument have been identified within the Rice science and enginee

This award is in support of the Research Experiences for Undergraduates site located the Rice Quantum Institute at Rice University. The REU program conducted by the Rice Quantum Institute (RQI) brings students from outside universities to Rice University for a ten-week interdisciplinary summer research program. Each student works directly within the research group of a faculty mentor from science and engineering departments within RQI. Each project is designed to be part of a long-range research program by the faculty mentor, but individual to the student and manageable within ten weeks. The students are collectively exposed to different disciplines by contact with a variety of research groups in other labs, weekly seminars by Rice grad students and frequent scientific and social interactions (as well as joint housing) with the other REU students. In mid-session, the students present brief computer presentations to each other and the PI of the context, goals, hurdles and long-range expected yield of their projects. During the final week, written reports are turned in, exit interviews are performed, and, on the last day, students present their work at the RQI Colloquium. This annual event, which assembles a large audience made up of REU students, of research groups and others from Rice, as well as interested outsiders from neighboring schools and industries, showcases research going on within the Institute. This site is co-funded by the Department of Defense in partnership with the NSF REU program, and by the Physics Division, the Division of Materials Research, and the Chemistry Division within the Directorate for Mathematical and Physical Sciences.

The University of Arizona is partnering with the Tucson Unified School District to implement and study a professional community designed to alleviate the mismatch between the expectations of student teachers in mathematics and science and their mentor in-service teachers. This vexing problem often arises when student teachers expect to implement reform-based pedagogies while their mentor teachers insist on traditional approaches. The project is creating a "third space," a professional community that includes 40 pre-service and 50 in-service teachers, university scientists and mathematicians, science and mathematics education faculty, and school district administrators. The third space is providing a neutral forum for the exchange of perspectives on issues of pedagogy with the expectation that student teachers would implement inquiry-based science and problem-solving mathematics pedagogies with the knowledgeable support of their mentor teachers. The project is being implemented in two low-income, culturally and linguistically diverse elementary schools with a comparison school used as a control.

The evaluation/research component is a qualitative study led by Horizon Research, Inc. The fundamental research question is whether the third space model establishes interpretive systems that foster enactment of inquiry-based and problem-solving teaching practices. Data collection will include all participants in the third space forum, but focuses on the pre-service and in-service teachers through written products and discussions of lesson design activities, videotapes of teaching by pre-service and in-service teachers, and analysis of comments made in a web-based forum. Instruments to be used are the Reform Teaching Observation Protocol (RTOP), the Experiences Patterns Explanations (EPE) framework, and the Inquiry-Application Instructional Model (I-AIM).

The main product of this project is the third space model and the research that supports its success. The model will be disseminated broadly and if replicated widely, it would represent a major improvement in the professional development of teachers in the areas of inquiry-based science and problem-solving mathematics.

The Center for HIV RNA Studies (CRNA) will focus on determining the structural and mechanistic bases of HIV-1 RNA dependent replication functions at the cellular, viral and atomic levels. Although considerable progress has been made over the past 25 years in understanding how proteins function in HIV-1 replication, comparatively little is known about how HIV-1 RNA structure, dynamics, trafficking, and interactions with proteins enable virus replication. Although HIV-1 RNA is exceptionally rich in biological functions, the paucity of detailed mechanistic insight into how these biological functions are executed is due to inherent difficulties in studying the structure and dynamics of RNA molecules. For example, it has been challenging to obtain high-resolution structural information for RNA and protein-RNA complexes using traditional X-ray crystallographic, NMR or cryo-electron microscopic approaches. It has also been difficult to study the functions and interactions of RNA molecules with proteins in vitro and in cells. The CRNA consists of a multidisciplinary team of structural biologists, chemists, cell and computational biologists, molecular biologists and virologists, many of whom are leaders in the study of HIV-1 RNA and the role of its structures in virus replication. They have developed and will further advance new approaches to overcome current technological obstacles, enabling mechanistic determination of the role of HIV-1 RNA structures and associated proteins in viral transcription, splicing, translation, packaging, particle assembly and interactions with restriction factors. The studies proposed herein will enable the CRNA to advance goals of clinical relevance, including the development of novel antiviral compounds, design of new strategies for the reactivation of latent proviruses, and the augmentation of host defenses against HIV infection. These studies will also result in the development of novel techniques that can be applied to all areas of RNA biology.

This CRPA project is about research on climate change impacts in the Amazonian rain forest and about motivating youth to consider science as a career objective. The project is an exhibit in Biosphere 2 in Arizona wherein a rain forest is maintained and will be used to augment the exhibit of large photos of scientists doing research. Particular attention will be paid to female scientists to motivate young girls. Biosphere 2 and the Girl Scout Council of Southern Arizona will collaborate to attract girls through free admission days to Biosphere 2.

These large photos will be equipped with sound and video so that as a visitor approaches the photo, the sounds of the forest as well as the researcher(s) will be heard. At this point the researcher, in the photograph, will begin a monologue with the visitor explaining what scientists are investigating and who the other workers are. In this monologue, the researcher will explain what they are doing specifically, why they are investigating this subject, and what they plan to derive as a scientific result. The exhibit will consist of fifty very large photographs (3x5 feet) with sound access via smart phones and headsets. In addition, there will be hands on equipment and docents for questions and discussion. The venue receives about 100,000 visitors per year consisting mainly of families, tourists, and clubs.

Through this exhibit, the researchers intend to motivate youth to develop interests in STEM topics. Girls are the main target audience. For families and tourists, the exhibit communicates the message of how science is being used to determine the effect of climate change on rain forests and how that would affect other aspects of weather and the global environment.

PROJECT SUMMARY/ABSTRACT Our long-term goal is to revolutionize the effectiveness of oncologic imaging for millions of Americans. Accurate and early detection of liver tumors and their associated vascular anatomy is critical for tumor staging, pre-surgical planning, and treatment monitoring. Unfortunately, with currently available contrast agents, computed tomography (CT) only shows a sensitivity of 60% for liver tumors <1 cm in diameter, even in modern studies with PET/CT. Available CT contrast agents are severely limited by poor liver and vascular enhancement, particularly for larger patients, and renal and allergic-type contraindications. Obesity is associated with higher risk of cancer mortality, yet current CT agents perform particularly poorly at the high-kVp CT settings needed to image such patients. All current CT agents use iodine, which loses up to 50% of its signal at high kVp. These so-called ?extravascular extracellular? agents equilibrate rapidly between the intravascular and interstitial fluid, and hence provide a ?washed out? appearance of critical structures. These small-molecule contrast agents are unable to quantify angiogenesis, which is a universal characteristic of tumors that correlates with aggressiveness. Unfortunately, prior experimental CT blood-pool contrast agents that can quantify angiogenesis have not been translated to clinical use in part due to slow bioelimination, complex synthetic processes, or toxicity. We developed a scalable process to produce a tantalum oxide nanoparticle contrast agent (TaCZ1) of prototype size (3.1 nm) that provides outstanding blood pool contrast, superior liver enhancement, and rapid renal clearance with no observable kidney pathology. However, reduction in the viscosity and osmolality of TaCZ is desirable to broaden its potential clinical value. Our Specific Aims are to 1) Increase TaCZ particle size to reduce osmolality and viscosity and improve imaging benefits; 2) Demonstrate TaCZ safety in preparation for clinical translation as a contrast agent; and 3) Show the agent's superior detection, characterization, and treatment monitoring of liver tumors. At project conclusion, we will have completed a major step toward clinical translation of a transformative tantalum-based blood-pool CT contrast agent, defined the ideal nanoparticle size for excellent safety, rapid renal clearance, and outstanding CT liver tumor imaging, and assessed this agent for primary and metastatic liver tumor detection, characterization, and treatment response.