Michael Rush - US grants

The Eagle-UnionCommunity School Corporation proposal seeks support to build upon and extend the work initiated with NSF support ( working partnership of many parts which is focusing on the use of modern technology for teaching science and mathematics. There are two major objectives of the project. E Objective I: Teachers in grades four through ten will integrate essential problem solving, critical thinking, and communications skills into the science curriculum using information technologies (electronic mail, online database searching, and CD-ROM). E Objective II: Each of the teachers will develop and implement at least one comprehensive student-based project. The projects will promote problem solving, critical thinking, and communication skills, and integrate the use of the information technologies. Over the three years of project support 120 teachers, 30 student teachers, and 5,600 students at in grades 4 - 10 will become involved in the program. The project leadership anticipates the involvement of an additional 5,000 students in each of the three years following completion of the NSF project.

9454331 Rush Eagle-Union Community School Corporation Institute for Science and Technology This 48 month project provides five-week institutes for 290 inservice and 40 preservice teachers of grades K-12. The goals of the project are to provide pedagogical and philosophical foundations for improving science education, develop strategies for increasing student learning of science, and develop a significantly improved delivery system to encourage creativity, problem solving, critical thinking, and communications. The project has four activities. The first is the Institute for Science and Technology. Through these summer institutes, teachers take two years to get fully trained and integrate technology into the curriculum. The second is the internships and mentorship program offered at places like the Indianapolis Zoo and Lilly Research. A third component is the "Teacher in Residence" who is selected each year to work with the project. Finally, there is a complementary preservice component with Purdue University that is funded locally. Fifty teachers are selected in the first year form Project INSITE. They receive 5 weeks of training over the two summers. This includes formal training in science, work experience, research experience, training on the Internet and telecommunications, etc. Several of these teachers will be selected to help as trainers for subsequent groups each of eighty teachers. Participants are initially from Indiana. Cost sharing is 30%.

? DESCRIPTION (provided by applicant): Approximately one-third of Americans are obese resulting in over $1,400 extra health care costs per capita each year in the United States, which makes obesity a major public health and economics issue. Unabated high caloric diets can lead to obesity and associated medical. Anti-hyperglycemic agents such as sulfonylureas and biologicals such as insulin control free glucose levels but do not necessarily prevent obesity. There is vast potential to discover new therapeutic agents to help prevent excessive carbohydrate related obesity. Nature provides broad chemical diversity, and natural products continue to be sources of new chemical scaffolds and new classes of compounds for a wide range of therapeutic agents. The research of this predoctoral training grant will be to discover natural product inhibitors of the gluconeogenic enzyme, fructose-1,6- bisphosphatase (FBP). FBP functions as a gluconeogenic enzyme without involvement in any other biochemical or metabolic pathways; undesirable side effects that are common to less specific targets can be avoided. Although the pharmaceutical industry has validated FBP as a viable anti-obesity target, the only promising compounds weakly bind to a cofactor receptor site. Therefore, ligands to the active site of FBP and potent inhibitors of any type remain undiscovered; the diversity of natural products represents an unexplored resource for lead compounds. The primary impediment to the discovery of natural product lead compounds is that most natural products exist in complex mixtures and are not compatible with most high-throughput screening approaches. To overcome this impediment, I have been developing high-throughput mass spectrometry-based assays that are designed for identifying active compounds within complex mixtures. Specifically, my preliminary data show that microbead affinity selection screening (MMASS; invented in the laboratory of sponsor Dr. van Breemen), which uses high resolution UHPLC-MS and metabolomics-type data processing, provides the selectivity and speed required for screening complex natural product mixtures. Using the inflammation target 15-lipoxygenase (15-LOX) to establish proof of concept, I enhanced the throughput of MMASS by approximately 100-fold and then applied it to the discovery of a 15-LOX inhibitors in extracts of 15 North American prairie plants used by Native American women for their anti-inflammatory properties. These assays resulted in the identification of quercitrin as a 15-LOX inhibitor in an extract of mermaid weed. To complete my dissertation research, I will use MMASS to test botanical extracts provided by the UIC/NIH Center for Botanical Dietary Supplements, natural product libraries and extracts of microbial cultures available at UIC for potential new inhibitors of FBP. The IC50 values and mechanisms of inhibition of the hits will then be determined. There is significant need to identify new compounds that inhibit FBP and tapping the chemical diversity of natural products will provide lead compounds with perhaps unique scaffolds and novel binding mechanisms.