Computational Applications in Diabetes and Endocrinology

NIH/NIDDK Education Project Grant R25 DK064122-01  05/01/03 – 04/30/08

Principal Investigator: Michael L. Johnson
Co-PIs:    Boris Kovatchev

 

Overall Goal

We develop a cross-disciplinary NIDDK educational program in Computational Applications in Diabetes and Endocrinology that integrates quantitative and computational strategies with diabetes and endocrine research in undergraduate, graduate, and postgraduate curricula at the University of Virginia (UVA). Development and implementation of an undergraduate summer research experience is assisted by three consultants - undergraduate math and biology faculty at Sweet Briar College (SBC; a small, technologically-oriented undergraduate women’s college near UVA) with whom the program directors have a productive, long-standing relationship re: educational development activities. The goal is a unique, innovative, curriculum-driven program that creates educational opportunities to attract students and fellows to careers in biomedical diabetes/endocrine research, with particular emphasis on quantitative applications. In this way, we hope to target historically under-represented disciplines in biomedical research in diabetes and endocrinology (math, stats, engr, comp sci, etc.).

A broad array of independently-funded projects in diabetes/endocrine research at UVA [spanning a range of hierarchical levels of organization: (i) sub-cellular/cellular; (ii) hormonal-patterning; (iii) endocrine-network; (iv) human, macroscopic; and (v) biobehavioral] will serve as content basis for the educational modules developed in this program. Students will derive unique benefit from attempts to replicate challenges presented by contemporary research, thereby providing skills needed to transition from undergraduate classroom to graduate education to professional career and beyond.

The instructional format will be modular, based on individual diabetes/endocrine research projects/questions. Tangible deliverables we propose to develop: (i) undergraduate research experience modules with problems sets, laboratory and project activities, and instructor lesson plans; (ii) advanced, graduate-level textbook, “Quantifying Diabetes: Data Analysis and Modeling Methods for Diabetes Research and Clinical Practice;” (iii) corresponding interactive CDs; and (iv) interactive web site providing links between textbook/CD content and research projects, and updated tutorial materials. Eventually, we plan to offer formal degree subspecializations in Biomathematics (BS/MS) and Computational Diabetes and Endocrinology (MS/PhD).

Content Basis

The research environment in diabetes and endocrinology at UVA has recently undergone a conceptual consolidation in terms of quantitative and computational applications. UVA thus finds itself at a particularly propitious time to develop and implement the proposed novel, cross-disciplinary educational program given the prominent positioning enjoyed by diabetes and endocrine research at the university, and the considerable existing momentum to aggressively further develop the associated basic and clinical research environment. As such, our proposed plan provides a unique opportunity to bring together, in a multi-educational-level curriculum-based strategy, currently-active basic and clinical biomedical researchers in the context of the increasingly important role that quantitative and computational applications are playing in contemporary biomedical research, in general, and diabetes and endocrine research, in particular. The proposed program will draw on this collective research experience to design contemporary curricular materials appropriate for all educational levels, focusing all the while on applications of computational, mathematical, and quantitative modeling, analysis, and interpretive approaches to diabetes and endocrinology.

Target Audience and Anticipated Outcomes

The proposed program’s multi-disciplinary and interdisciplinary emphasis on quantitative applications to diabetes research is being designed specifically to attract students and postdoctoral fellows from scientific disciplines underrepresented in disease-oriented biomedical research (such as mathematics, statistics, engineering, informatics, computer science, and computational sciences) and encouraging them to apply their expertise to, and pursue careers in, research relevant to diabetes and other endocrine diseases and disorders.

As such, anticipated outcomes of this program’s educational activities are to:

(i)  inspire interest and facilitate developing quantitative expertise of future diabetes and endocrine researchers;

(ii)  provide an educational model to facilitate interfacing the biomedical sciences of diabetes and endocrine research with quantitatively-oriented sciences; and

(iii)  develop closer, productive, collaborative relationships between those engaged in biomedical diabetes and endocrine research and those engaged in education.

Uniqueness

The proposed educational program will be unique in several ways:

(i)  for the first time, the integration of genetics, physiology, pathology, and treatment of diabetes will be brought together in the context of a single educational program devoted to mathematical and computational methods;

(ii)  the content basis for each of the proposed educational initiatives will be based directly on ongoing contemporary research projects in diabetes and endocrinology at UVA;

(iii)  the program will engage with all educational levels, thus smoothing the transition from undergraduate to graduate and postgraduate education and, ultimately, to careers in diabetes and endocrine research; and

(iv)  the program will target a diverse audience of students and postdoctoral fellows, those with quantitative and computational backgrounds wishing to learn applications of their expertise to research in diabetes and endocrinology, as well as those active in diabetes and endocrine research wanting to expand their knowledge base by adding these increasingly-important quantitative analytical and interpretive abilities.

Program Features

The featured elements of the proposed program are:

(i)  an undergraduate summer research experience in computational diabetes and endocrinology;

(ii)  a graduate course in “Computational Methods in Diabetes and Endocrinology;”

(iii)  a graduate/postdoctoral-level seminar series; and

(iv)  professional development workshops.

Structure of the Proposed Modular Instructional Activities

The undergraduate summer research experience and the graduate course will be built around a series of relatively independent modules that focus on specific aspects of diabetes and endocrinology. The level of sophistication of the modules will vary with the target-student level, but all modules will be developed in the following four stages:

(i)  Stage 1 will serve as a general introduction to the diabetes/endocrinology-oriented biological and biomedical research questions to be considered; background will be provided and the problems(s) at hand will be put into appropriate perspective; information will be offered primarily in the form of lectures by UVA faculty whose research forms the basis of the modules;

(ii)  Stage 2 will be a student brainstorming session overseen by the faculty where students will propose strategies for solution and identify needed analytical tools; faculty will provide introductory and supplementary instruction required for identifying and applying these tools;

(iii)  Stage 3 will engage students in applying the solution strategies decided upon in the previous stage on data sets gathered from faculty research; overseeing faculty will provide guidance and maintain close interaction by assisting with this process, however, students will work in quite independent manner, interacting with supporting faculty primarily through inquiry, not through formal lectures (by design, some fraction of particularly challenging data sets will be included for the students as examples of real-world confounding situations typically encountered in research settings); and

(iv)  Stage 4 will have students prepare and deliver formal presentations, including interpretation of results from their data modeling and analysis, discussions of alternate solution strategies, and statistical issues; overseeing faculty will provide formal guidance and supervisory support, as well as intellectual input regarding biological-biomedical interpretations.

Undergraduate Summer Research Experience

The UVA School of Medicine offers summer research internship opportunities to qualified undergraduates who are considering a possible career in biomedical research. The goals of the program are to expose undergraduate students to laboratory research, to familiarize them with the opportunities that exist for careers in biomedical research. The program runs for ten weeks each summer and includes three major components: (i) a hands on research project with a faculty member where the student is exposed to contemporary methods and problems in biomedical research; (ii) a series of workshops in which students are exposed to a variety of advanced research techniques that they are unlikely to see in individual laboratories, including tours and demonstrations of some of the core research facilities at the university; and (iii) a Distinguished Lecturer Series in which participants are exposed to a wide variety of research topics through seminars presented by internationally recognized scientists.

Graduate Course “Computational Methods in Diabetes and Endocrinology”

The proposed graduate course in “Computational Methods in Diabetes and Endocrinology” will serve as a focused introduction for graduate- and postgraduate-level students to obtain a comprehensive introduction to contemporary quantitative methods applied to basic and clinical diabetes and endocrine research. It is anticipated that a graduate/postgraduate-level text will emerge as a consequence of this course development activity, tentatively entitiled “Quantifying Diabetes: Data Analysis and Modeling Methods for Diabetes Research and Clinical Practice,” the primary author of which will be Boris Kovatchev, with contributions from Drs. Bill Clarke, Dan Cox, Linda Gonder-Frederick, Michael L. Johnson, Gene Barrett, Tony McCall and others. Proposed course and text topics include, but are not limited to:

Seminar Series

The proposed course activities will be complemented by a seminar series, “Application of Computational Methods to Diabetes Research.” Participating program faculty and external researchers involved in diabetes and endocrine research will be invited to present current results from ongoing projects in an anticipated once-monthly format (4/fall semester; 4/spring semester).

Workshops

(i) The clinical blood glucose optimization problem of diabetes;

(ii) History of quantifying characteristics of T1DM and T2DM;

(iii) Error-grid analysis;

(iv) Behavioral determinants of T1DM control;

(v) Risk analysis of blood glucose data;

(vi) Use of self-monitoring blood glucose (SMBG) data for evaluation of patients’ glycemic control;

(vii) Stochastic modeling of blood glucose fluctuations;

(viii) Network modeling of blood glucose dynamics;

(ix) Analysis of continuous glucose monitoring (CGM) data.

Three professional development workshops, “Analysis of Hormone Pulsatility,” “Quantitative Methods in Diabetes Research,” and “Analysis of Circadian Rhythms” are expected to be offered annually by the proposed educational program.

The first of these workshops, “Analysis of Hormone Pulsatility,” has already been offered by UVA’s Center for Biomathematical Technology, in conjunction with the NSF Center for Biological Timing and UVA’s NIH-sponsored General Clinical Research Center (see Appendix 4). It has presented annually, in January 1999, 2000, 2001, and 2002, and will be presented again in January 2003. Organized by Michael L. Johnson, it has been delivered by Drs. Johnson and Evans in a three-day format.

The experience of having offered this workshop numerous times has prepared the instructors and lecturers in regard to pedagogical issues that have commonly arisen in presenting this material to quantitatively novice audiences. It is expected that this experience will be valuable when adapting this workshop’s educational methods during design and implementation of the other two proposed workshops.

Principal Investigator

Dr. Michael L. Johnson has a Ph.D. in biophysics with a specialty in modeling of biological processes.  Johnson has written more than 280 publications and edited 8 books, the majority of which involve mathematical modeling of various biological processes, e.g. Methods in Enzymology vol. 210, 240, and 321, and Methods in Neuroscience vol. 28.  Johnson is the biomathematician for the UVA General Clinical Research Center, the only biomathematician on the staff of any of the NIH General Clinical Research Centers.

Advisory Committee

Dr. Gene Block, Provost for the University of Virginia, Director of the Center for Biological Timing, and Professor of Biology, is a distinguished circadian biologist with a demonstrated commitment to educational initiatives;

Dr. Michael Thorner, Professor of Endocrinology and Metabolism and Chair of the Department of Internal Medicine;

Dr. Daniel Cox, Professor of Psychiatric Medicine and Director of the Center for Behavioral Medicine Research;

Dr. William Clarke, Professor of Pediatrics and a pediatric endocrinologist with 20 years of experience in diabetes research and clinical practice;

Dr. William Evans, Professor of Endocrinology and Metabolism, Associate Chair of the Department of Internal Medicine, and Director of the Multidisciplinary Training Program in Clinical Investigation;

Dr. Joel Hockensmith, Associate Professor of Biochemistry and Molecular Genetics, Assistant Dean for Graduate Research and Training, Director of the Office of Graduate Programs, and Director of UVA’s Summer Research Internship Program;

Dr. Loren Pitt, Professor of Mathematics; and

Dr. Jeff Holt, Associate Professor of Mathematics.