# CELL BIOLOGY OF LOCOMOTION & CHEMOTAXIS OF LEUKOCYTES

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1989 · $179,109

## Abstract

The long term goal of this project is to understand at a
fundamental level the response of the polymorphonuclear
leukocyte (PMN) to local injury of the body.  The PMN detects
specific chemical signals that emanate from the site of insult.  It
crawls toward the signal and, upon reaching the source, it ingests
and kills bacteria.  Thus, the PMN provides a critical first line of
defense against infection and to understand the mechanistic basis
for its behavior is of obvious health relavence.

Detection of chemical signals by the PMN is accomplished
through transduction at the cell membrane of specific receptors
coupled to G-proteins.  Second messengers activate the motile
apparatus to polarize the cell and set it into motion.  The
polymerization of actin is critical to the response.

The present goal is to determine how the chemical signals evoke
actin polymerization and how this contributes to the motile
response.  The first aims are structural: to locate the subcellular
sites of actin polymerization following focal stimulation (via a
patch pipette) and diffuse stimulation; determine the polarity of
the evoked filaments in relation to the membrane.  Evoked
polymerization is monitored using modified actins whose
fluorescent signals increase upon polymerization.  Filament
polarity and the relation to the membrane will be determined by
electron microscopy following labeling with the S-1 fragment of
myosin. The next aims are biochemical: indentify the control
mechanism for the stimulus evoked actin polymerization.  The
method is to stimulate intact cells, extract them and probe the
extracts for evidence of regulatory activity (including changes in
free filament ends, proportion of barbed and pointed free ends,
capping and cutting).  We shall also determine if the activities so
identified depend on known actin binding proteins.  The last aims
are also biochemical:  identify pathways linking transduction to
actin polymerization.  We shall start by developing an in vitro
transduction system using as endpoints the activities
characterized in Aim 2.

## Key facts

- **NIH application ID:** 3129334
- **Project number:** 5R01AI019883-07
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** SALLY H ZIGMOND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $179,109
- **Award type:** 5
- **Project period:** 1983-09-01 → 1993-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129334

## Citation

> US National Institutes of Health, RePORTER application 3129334, CELL BIOLOGY OF LOCOMOTION & CHEMOTAXIS OF LEUKOCYTES (5R01AI019883-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129334. Licensed CC0.

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