# STRUCTURE FUNCTION STUDIES OF MUSCLE AND HEART

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 1992 · $223,536

## Abstract

The broad aim of this research is to establish the molecular basis of
skeletal and cardiac muscle assembly and function in the normal tissue
and in heart failure.  The major present goals are (1) to use molecular
genetics to study the length dependency of cardiac muscle (Starling's law
of the heart) by defining the amino acid residues responsible for the
length sensing mechanism.  Specific manipulations of the structure of TnC
will be correlated with alterations in the cardiac and skeletal
length-tension curves. (2) We propose to investigate the basis of
cooperativity in the Ca2+-switching processes of the thin filaments in
cardiac muscle.  Also, by examining the interactions of force modifying
compounds, such as TFP as well as cardiotonic agents, with the Ca-binding
proteins and their genetic variants, we will examine whether the
hydrophobic residues of TnC participate in setting the cooperativity
level in the Ca-force relations in muscle.  In addition we will study the
specific role of the central helix in TnC and calmodulin in the switching
mechanisms.  In particular, we propose to determine whether the central
linker between the N- and C-terminal lobes is essential to function.
Further, by combining the mutation studies with computer simulations, we
will examine whether the bending of the central helix that could cause
compaction of the molecule, is essential for the molecular dynamics
related to ligand binding, and also whether the highly conserved arginine
residues are implicated in this function. (3) We also propose to
characterize the properties of cofactor-B.  Cofactor-B, discovered in
this lab, is a protein essential for reconstitution of extracted fibers.
Our goals are to purify, clone, mutate, determine isoformic diversity,
and study the expression of cofactor-B in normal tissue as well as during
the development of cardiomyopathy of the Syrian hamster.  A major
hypothesis is suggested that cofactor-B controls the link between
the weak and strong cross-bridge states.

## Key facts

- **NIH application ID:** 3156643
- **Project number:** 2R01AR033736-07A1
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** JAGDISH GULATI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $223,536
- **Award type:** 2
- **Project period:** 1992-09-18 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156643

## Citation

> US National Institutes of Health, RePORTER application 3156643, STRUCTURE FUNCTION STUDIES OF MUSCLE AND HEART (2R01AR033736-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156643. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*