David Ellis - US grants

Taxol, a diterpenoid extracted from tissues of the slow growing Taxus brevifolia Pacific yew) tree, shows considerable promise as an anticancer drug. However, a reliable large scale supply of taxol is not available. Tissue culture of Taxus may provide an alternative supply. Unfortunately, taxol, by binding to microtubules, is likely toxic to most cells; thus the development of a microculture system for the high level production of taxol may require the differentiation of cell types capable of partitioning the toxic compound away from actively dividing cells. To achieve this, we propose to develop a nodule culture system for Taxus based on work done with other woody plants. Nodules are dense cell clusters which form, grow and multiply as a cohesive unit. Nodules are particularly attractive for taxol production as they display a high degree of both cellular and tissue differentiation. Nodule cultures can theoretically serve as a production system for taxol since the outer rapidly dividing cell layers maintain the growth needed for biomass proliferation while the inner differentiated cells provide an isolated location for taxol production. Nodule cultures will also serve as a manipulatable model for studies of taxol biosynthesis. We will investigate the conditions which affect nodule development, growth and tissue HPLC taxane profiles. To understand the requirements taxol production, immunocytological localization of taxanes within intact plants and the seasonal environmental influences will be determined. Such information will be used to deduce the conditions required for maximal taxol synthesis in nodule cultures. The influence of batch and perfused bioreactor systems on production will also be determined. Once the development of a Taxus nodule system for enhanced taxol production is accomplished, then it can be used to extend the research to the elucidation of the enzymes and genes involved in taxol synthesis.

The capstone experience to the Applied Mathematics Undergraduate Program is concentrated in a mathematics modeling course, requiring prerequisite materials in computer programming, differential equations, linear algebra, and mathematical statistics, followed by senior project courses. In these project courses an industrial environment is simulated, attempting to give students the best possible environment for professional positions as applied mathematicians. This project is updating the existing laboratory resources with four high performance IBM-compatible PCs, 80486 based, and two SUN SPARCstation machines, including common industrial mathematics software. This enhancement to the computer laboratory is allowing the institution to incorporate intense, realistic computational assignments as part of the capstone experience in undergraduate applied mathematics.

9402301 Ellis A group of six science and technology centers across the country proposes to form a pilot collaborative effort to establish connections to NSFNET. These institutions share the vision that access to the resources provided via NSFNET will significantly enhance their ability to achieve their common missions and goals in providing informal science education for students, teachers, and the general public. Further, it is expected that this group of institutions will serve as a model for other museums and represents the vanguard in what will become a general movement for science and technology centers to become full participants in this national communication network. The partner institutions of this collaboration are: The Franklin Institute (PA), Liberty Science Center (NJ), Museum of Science (MA), Center of Science and Industry (OH), Oregon Museum of Science and Industry (OR), St. Louis Science Center (MO), The Science Place (TX). Connection to NSFNET will bring a wide range of remote information resources within immediate reach of museum researchers, educators, and visitors. Specifically, access to the NSFNET will help the partners of this pilot group to improve operations in the areas of teaching, research, and service.

9500433 Ellis The "Research Experiences for Undergraduates" in the Physics Department of the University of Toledo will be continued. This program places eight students each summer in the research programs of the Department, which cover a number of topics in Physics and Astronomy. The students will be given a number of opportunities to interact professionally. ***

PHY-9731880- David Ellis, University of Toledo

The "Research Experiences for Undergraduates" in the Physics Department of
the University of Toledo will be continued. This program places eight
students each summer in the research programs of the Department, which cover a number of topics in Physics and Astronomy. The students will be given a number of opportunities to interact professionally. Available research fields include astronomy, astrophysics, atomic physics, biophysics, condensed matter physics, materials science, and optics. Student projects will include a written report and an oral presentation of results. Also, students will participate in a weekly seminar, with speakers including students, faculty, and visiting researchers. Students will be recruited nationally, and free housing will be provided, so that students from various regions can meet each other and broaden their view of the diversity of physics programs in the U.S. Group social activities and field trips will enhance students' overall experience.

This project will establish a long-term collaboration between the Mathematics Department of San Francisco State University (SFSU), one of the country's largest centers of education for minority students, and the Mathematical Sciences Research Institute (MSRI), one of the world's leading mathematical research centers. Each semester this collaboration will revolve around an undergraduate topics course at SFSU based on one of the emphasis programs at MSRI that semester.

The SFSU-MSRI collaboration will be taught by a faculty member in the SFSU Mathematics Department (a different person each semester). This person will participate in the MSRI program associated with the chosen topic during the semester and will act as a bridge between SFSU students and the research mathematicians at MSRI. The SFSU-MSRI collaboration course will feature monthly talks by leading mathematicians who are visiting MSRI to participate in its program.

All lectures in the SFSU-MSRI collaboration course will be made available to the world through MSRI's streaming video technology. This technique, pioneered by MSRI for publishing mathematical lectures on the World Wide Web, uses one browser window to show the slides of the talk and another to show the speaker while the sound flows smoothly. Because research mathematicians rarely pitch work to undergraduates, as they will in the SFSU-MSRI collaboration course, the entire set of lectures will be made available on CD-ROM for dissemination to other universities.

So that SFSU students and faculty can have the library resources needed to prepare for MSRI programs, mathematics books will be purchased for the SFSU library. Each semester, SFSU will emphasize the purchase of books for the library related to the topic of that semester's SFSU-MSRI collaboration course.

This project also will support four SFSU graduate students each year. These students will participate in various activities at MSRI each semester.

SFSU will become an Academic Sponsor of MSRI. Membership benefits include sending two graduate students, expenses paid, to the MSRI Summer Program, inviting speakers from MSRI with expenses partially paid, receiving the preprint series, and financial support for conferences.

0091749
ELLIS

The Museum of Science in Boston is conducting a workshop/symposium that will focus on the question of how best to address the issue of enhancing public understanding of major, on-going research efforts. The workshop will begin a critical discussion among researchers and some of the most prominent practitioners of informal public education in the areas of science, engineering and technology. The discussion will explore possible directions that might be taken in regard to disseminating information about research to the public and in increasing the public's understanding of the role and possible implications of this research. Issues to be examined include:

The scope and aspects of research upon which to focus
The present obstacles to public understanding
The advantages and disadvantages of different approaches for disseminating information
Costs and time frames of different approaches
How to encourage and implement collaboration and networking among institutions that have the goal of increasing public understanding.

The general goal of the workshop is twofold: to provide feedback that will inform the creation of new programs to address the issue of enhancing public understanding of research and to share ideas among institutions that have a common purpose.

The analysis of large complex data sets poses a major challenge for computational mathematics. Topological Data Analysis (TDA) applies concepts from algebraic topology to address this challenge. Topological techniques have been used successfully in engineering and biology but are seldom applied to the analysis of genomic data. In cancer genomics, the identification of copy number aberrations (CNAs) such as gains and losses of DNA segments is an important problem because CNAs are known to contain cancer genes and therefore to be involved in misregulation of key signaling pathways. CNAs may occur independently or may co-occur. The latter are believed to act synergistically and therefore result in unforeseen consequences. For example, the finding that CNAs in 8p12 and 11q13.3 are co-amplified in some breast cancers led to the discovery of functional interactions between the MYC and the TP53 pathways. Such interactions offer an important paradigm for cancer research because many tumors are believed to use similar mechanisms for their progression. Identification of co-occurring CNAs has traditionally been hindered both by the large sample sizes required to find co-occurrences and by the lack of mathematical methods to identify them efficiently. Recently, large microarray-based data sets have become available for breast cancer. The proposed research aims to develop a new TDA-based method to detect independent and co-occurring CNAs in breast cancer. In the proposed approach each CNA profile is characterized by a set of biologically-meaningful topological spaces. Topological invariants of these spaces (i.e., Betti numbers) will be used to de-noise the data and identify CNAs. This project will yield broadly-applicable methods for: (1) representing complex data sets in forms that are amenable to topological analysis; (2) determining the statistical significance of TDA results; (3) computing topological invariants from large data sets.

Rapid advances in the sciences have generated large, complex data sets of unprecedented proportions. New mathematical methods are urgently needed in order to solve fundamental problems in the analysis of such high-dimensional data. In the field of genomics, thousands of measurements have been obtained with the goal of unveiling molecular signatures that characterize essential biological processes. This field has significantly influenced the direction of breast cancer research because of its potential for differentiating various subtypes, pathways and prognoses of the disease. Currently, the major approach to detecting genomic signatures is focused on the identification of single independent events. However, there is increasing evidence that copy number aberrations (CNAs)-- such as amplifications and deletions of the genome--are not always independent of one another; rather, they may co-occur with synergistic and unforeseen consequences. For example, co-occurring CNAs detected in breast cancer have led to the identification of cross-talk between different signaling pathways. The systematic search for co-occurring CNAs has been hampered by a lack of mathematical methods adequate to identify them. The PI proposes to develop new methods in Topological Data Analysis to identify co-occurring CNAs in breast cancer. Further, because copy number changes are associated with other diseases and with evolutionary processes, this project will have important impacts across the sciences, both basic (e.g. evolution and development) and applied (e.g. diseases with a genetic component such as cancer, autism and multiple sclerosis). The proposed research will advance the field of mathematical genetics/genomics with new tools for analyzing complex interactions among genetic elements in genetic/genomic data. The methods developed also have the potential for extension to identify co-occurring events in large, complex longitudinal data sets. Furthering its broader impacts, the project will implement a series of public lectures on real-life applications of computational mathematics with special outreach to local school teachers, students and professionals.