# PROBING CELLULAR INTRACELLULAR CALCIUM SIGNALING AND SENSING THROUGH COMPUTATION

> **NIH NIH R35** · LOYOLA UNIVERSITY CHICAGO · 2020 · $324,911

## Abstract

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Intracellular Ca signaling Kekenes-Huskey, PM. University of Kentucky
Probing cellular intracellular calcium signaling and sensing through
computation
 Calcium signaling regulates biological function across a broad range of tissue types and species,
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but several factors known to control Ca -dependent signaling efficiency have challenged both compu-
tational and experimental inquiry. There are significant gaps in our understanding of how nuances in
protein structure and dynamics as well as their intracellular distribution affect fundamentally important
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processes including how 1) Ca accumulates within localized intracellular regions 2) proteins bind
2+ 2+
Ca with high affinity 3) Ca 'sensor' proteins regulate signaling cascades. Detailed knowledge about
these topics and their inter-dependencies would yield new paradigms in how we view biology, physiology,
and health. Computer simulations are attractive in this regard, both for describing phenomena that are
difficult to directly resolve experimentally, as well as forming integrative conceptual models spanning
these underlying topics. However, several prominent hurdles render such transformative simulations
cost-prohibitive. Among these, reducing the intractable computational expense involved with model-
ing fine detail processes like transport governed by sub-nanometer to micron scales, atomistic-scale
thermodynamic factors shaping ion/protein binding, and long-range forces that promote protein/protein
signaling pathways, is likely the foremost challenge in biophysics today. In this proposal, we outline sev-
eral multi-scale algorithmic advances that will ease this challenge, while providing insight into important
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Ca -driven processes that orchestrate life:
 Theme 1 Tuning Ca2+ sensing and response at the molecular level. In this theme, we will
 develop new paradigms for understanding nature's tricks for controlling specificity and kinetics in
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 Ca sensing functions.
 Theme 2 Automated detection of disease-associated morphological changes in cardiac
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 cells and their influence on Ca homeostasis. In this theme, our lab will leverage troves of
 underutilized microscopy data to answer questions regarding the role of intracellular organization
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 in shaping Ca signaling.
 Theme 3 Molecular mechanisms of cellular-scale control via the P2X4 receptor. In this
theme, we will establish strong links between molecular scale protein structure/function and their
control of cellular-scale signaling outcomes.
1

## Key facts

- **NIH application ID:** 10003329
- **Project number:** 5R35GM124977-04
- **Recipient organization:** LOYOLA UNIVERSITY CHICAGO
- **Principal Investigator:** Peter Michael Kekenes-Huskey
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $324,911
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003329

## Citation

> US National Institutes of Health, RePORTER application 10003329, PROBING CELLULAR INTRACELLULAR CALCIUM SIGNALING AND SENSING THROUGH COMPUTATION (5R35GM124977-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10003329. Licensed CC0.

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