Faculty Student Mentoring Program – Mini Grant Application 2012-13
Diana W. Verzi, Professor of Mathematics dverzi@mail.sdsu.edu
760-768-5531 ( on campus dial 6-5531) SDSU-Imperial Valley Campus
Abstract
Dr. Satchi Venkatamaran of the Department of Aerospace Engineering and the Computational
Science and Research Center (CSRC) has nominated Dr. Diana W. Verzi, Deparment of
Mathematics and Imperial Valley Campus, for a mini-grant to fund the cost of research and
presentation incidentals in working with undergraduates from SDSU-Imperial Valley Campus
(SDSU-IV) in mathematical models for the interdependence of intra-cellular calcium density and
insulin release in pancreatic beta cells.
Pancreatic beta cells secrete insulin, the hormone that maintains blood plasma glucose within
narrow limits. Insulin allows muscle to take up glucose for immediate energy, and causes the
liver and fat cells to store glucose. Diabetes is a disease in which glucose is chronically elevated,
leading to blindness, kidney failure, limb amputation, cardiovascular disease, and death. Last
year, a group of four mathematics majors from IV campus were supported by FMSP to study
calcium influx/efflux as a second messenger for regulating membrane oscillations that lead to
insulin release. Models were developed and fit to data supplied by NIH, successfully recovering
frequency and magnitude of calcium dynamics, but lacking in qualitative behavior. Students
reported results in a talk at the SDSU Student Research Symposium (SRS), and in a poster and
the Society for Industrial and Applied Mathematics (SIAM) annual meeting. They have also
contributed to a paper. This year’s research will be added to that paper and the plan is to submit
it for publication summer 2014.
During the coming year, our ongoing research will consider the effect of intra-cellular calcium
buffering from the endoplasmic reticulum (ER), proposed to fine-tune calcium levels at a local
level. Our work will follow a path suggested by Dr. Arthur Sherman, director of the
Mathematical Cell Modeling Section (MCMS) of the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH). Dr. Verzi
collaborates with Dr. Sherman and plans a sabbatical with the MCMS within the new few years.
Project Description
Academic year 2013-14, Dr. Verzi and three Imperial Valley (IV) Campus undergraduate
students will study how membrane potential (V) and calcium (Ca++) oscillations from internal
and external sources are used to regulate insulin secretion. Potassium channels and Ip3
receptors will be considered as mechanical elements that indirectly affect the level of free
intracellular calcium levels within the cytosol. The students are supported by NSF-STEM
scholarships out of SDSU Computational Science and Research Center (CSRC), and this study
will produce simulations, or computational studies, based on physics and differential equations
that describe diabetes-related changes in the chemistry, activity and morphology of pancreatic
beta cells. Two students are continuing in my research group from last year, and will participate
in the CSRC program this year as seniors. The third student joined by group last spring and has
been accepted into the CSRC scholarship and workshop program for academic year 2013-14.
Cooperative efforts between Dr. Venkatamaran and Dr. Verzi
Students researchers will participate in weekly CSRC research skills workshops and colloquiums
at main campus, under the direction of Dr. Venkatamaran, to present and consider a variety of
research topics. Dr. Verzi is a researcher with CSRC, recruiting students from the IV campus to
consider graduate studies and careers in research. She will join the students in colloquium
attendance when presentation is within the scope of their joint research area. On these trips, Drs.
Venkatamaran and Verzi will meet with the students to jointly review and support their research
efforts and plan for future study.
Students will meet with Dr. Verzi one morning per week to report findings and receive guidance
for continued work. Dr. Verzi builds on her previous work for activity and calcium regulated
structural changes in the central nervous system for hippocampal dendritic spines (Verzi, 2004;
Verzi et al., 2005; Verzi and Baer, 2005). Students will report on this year’s work at the SDSU
SRS. Plans for this year are to bring the students to San Diego for two days with an overnight
stay, allowing them more time to attend other sessions and view the work of other students.
Students in the research group register for Math499 Special Study, so that I may apply for an
Instructionally Related Activity Grant to cover the cost of this field trip in March, 2014.
The NSF-STEM scholarship program supports student studies, but does not cover the cost of
their weekly required attendance in the colloquia and workshops. The FSMP mini-grant is
requested to contribute to student travel and parking expenses for the 112 miles between Imperial
Valley and main campuses, and to defray the cost of duplication, equipment, software and
ongoing recruitment.
Recruitment Plan
Students will give a talk about their research, the FSMP, and the CSRC NSF-STEM scholarship
program to sophomores at Imperial Valley [community] College, the feeder school for SDSU-IV
Campus. The IV Campus is upper-division only with respect to the hard sciences, and both the
community college and IV campus are Hispanic-serving institutions, supporting efforts to
increase representation of minorities in research and graduate programs in the hard sciences.
Statistics demonstrate that the time for undergraduates to think about graduate school is when
they are sophomores, so that we need to recruit them even before they enter IV Campus.
Presentation by mentored students and application handouts will recruit new mathematics
majors, mentored student researchers and NSF-STEM scholars to support this effort.
Mathematics and psychology remain the only majors from the college of sciences offered at the
IV Campus. While the psychology major is part of our 4-year undergraduate program,
mathematics remains a 2+2 program with the community college. With faculty outreach efforts,
supported by programs like the FMSP, I am proud to report that minority students from our
mathematics program have been accepted into graduate programs in mathematics, computational
sciences and medical school.
Research and Training Plan
Fall 2013
Students will gain knowledge in stochastic modeling and numerical methods, along with Matlab
programming and research techniques from Stat550 Applied Probabillity. They will further gain
insight into the world of research by attending weekly workshops and colloquia sponsored by
CSRC.
Specific to the planned research, they will research recent articles about calcium released from
internal stores and suggested models for recovering these contributions, as suggested by Dr.
Sherman. They will alter the programs written last year and validate their code by returning
graphs from earlier works (Fall C et al., 2002; Sherman A, 2005, Bertram et al., 2004,
Jahanshahi et al., 2009). Plan for utilizing undergraduate researchers is to have them alternate
emphasis between programming and simulation, or model research/analysis and reporting
results.
We will build upon last year’s work to consider the effect of the release of buffered calcium from
the endoplasmic reticulum (ER) on calcium and membrane potential kinetics, with appropriate
flux terms. Since acetylcholine (Ach) is an important potentiator for insulin secretion,
promoting the production of IP3 and dumping the stores, the ER should strongly influence
calcium kinetics, and all calcium-dependent processes within the beta cells.
Spring 2014
Students will continue to gain knowledge of theoretical models and numerical methods for
research in Math336 Mathematical Modeling, and by attending CSRC sponsored workshops and
colloquia. They will run simulations to fit parameter values and kinetics that return results from
measures taken at the University of Virginia (Charlottesville) Pancreatic Cell and Islet Isolation
Core, supplied by Dr. Craig Nunemaker, Director.
Students will prepare a talk about the work at the SDSU SRS, and contribute to writing a paper
to be submitted for publication summer 2014. They will attend CSRC Applied Computational
Science and Engineering Student Support (ACSESS) Conference in March 2014, along with Dr.
Verzi. In May 2014, they will present at the SDSU-IV Student Research Symposium, followed
by presentation of their work at the SDSU Student Research Symposium in San Diego.
References
1) Computational cell biology , edited by CP Fall, ES Marland, JM Wagner and JJ Tyson.
Springer-Verlag, NY (2000).
2) Bursting-The genesis of rhythms in the nervous system, Coombes and Bressloff ed. Ch
2: “Negative calcium feedback: The road from Chay-Keiser”, by Sherman A. World
Scientific Publ. Pte. Ltd. (2005).
3) The phantom burster model for pancreatic beta-cells (2000) Bertram R, Previte J,
Sherman A, Kinard TA, Satin LS. Biophys. J 79(6), 2880-92.
4) Bertram R Sherman A (2004) A calcium-based phantom bursting model for pancreatic
islets. Bull Math Biol 66, 1313-44.
5) Metabolic and electrical oscillators (2007) Bertram R, Sherman A, Satin LS. Am J
Physiol Endocrinol Metab 293, 890-900.
6) Multiscale modeling of electrical and intracellular activity in the pancreas: The islet
tridomain equations (2009) Goel P and Sherman A. Multiscale Model. Simul. 7(4), 16091642.
7) Calcium and glycolysis mediate multiple bursting modes in pancreatic islets (2004)
Bertram R and Sherman A. J. Biophys. 87, 3074-87.
8) Carter JD, Dula SB, Wu R, Nunemaker CS. A practical guide to rodent islet isolation.
Biological Procedures Online 11(1), 3-31, 2009.
9) Jahanshahi P, Wu R, Carter JD, and Nunemaker CS (2009) Evidence of diminished
glucose sensitivity and endoplasmic reticulum function among non-oscillatory pancreatic
islets. Endocrinology 150, 607-15.
Budget for FSMP funds by semester
Fall, 2013
Contribution to mileage for
students carpooling to
CSRC weekly
Printing, copies,
computational equipment
and supplies
$750
15 trips at 224 miles
roundtrip
$250
Spring 2014
Contribution to mileage for
students carpooling to
CSRC weekly
Printing, copies,
computational equipment
and supplies
$750
$250
15 trips at 224 miles
roundtrip