# TOXOPLASMA GONDII:  CELL BIOLOGY AND GENETICS

> **NIH NIH R01** · DARTMOUTH COLLEGE · 1988 · $195,346

## Abstract

The long term objective is to understand, as completely as possible, the
host-parasite relationship in cultured cells and in animals infected with
Toxoplasma gondii, an obligate intracellular protozoan parasite.  The first
specific aim is to determine the mechanism by which gamma interferon (INF)
inhibits the growth of T. gondii in cultured cells.  This mechanism appears
to involve the induction of host cell enzymes that degrade tryptophan to
kynurenine.  The enzymes responsible for this degradation will be assayed
and characterized.  The role of the INF-induced degradation of tryptophan
in the antitoxoplasma effect will be studied by using mutant host cells
that cannot be induced to make the degradative enzymes and by using
inhibitors of these enzymes.  The possibility that tryptophan degradation
products are toxic to T. gondii will be examined as will the possibility
that trytophan levels in the INF treated host cell's pool are too low to
support parasite growth.  The second aim is to examine the in vivo
effectiveness of murine gamma-INF in mice infected with T. gondii.
Experiments will measure protection against a lethal challenge dose,
activation of peritoneal macrophages, and the metabolism of radioactive
tryptophan.  Recovery from toxoplasmosis is probably mediated primarily by
cellular immunity.  One aspect of this immunity could be the production of
lymphokines such as gamma-INF.  In the absence of adequate cell mediated
immunity, toxoplasmosis is a serious infection in immunosuppressed patients
and especially in the victims of AIDS.  The other persons at high risk of
severe toxoplasmosis are unborn fetuses.  Toxoplasma gondii causes severe
congenital defects when pregnant women are infected.  Some of these
infections result from the ingestion of oocysts excreted in the feces of
infected cats.  The third aim is to produce a safe and effective feline
vaccine that can prevent this transmission.  The principle of the vaccine
is that the critical antigens for feline immunity are expressed on the T.
gondii gametes that are produced only in cat intestinal epithelium.  The
vaccine will consist of a mutant parasite that cannot make one gamete but
can make the other.  Without both gametes, infectious oocysts cannot be
excreted but one gamete may be sufficient to immunize.  The fourth aim is
to isolate and characterize more mutants of T. gondii and use them in
genetic crosses to define linkage groups of the parasite genome.  These
mutants will also be used to analyze the events of meiosis, which might be
a single step process in T. gondii and other related parasites such as
those that cause malaria.

## Key facts

- **NIH application ID:** 3125652
- **Project number:** 5R01AI014151-11
- **Recipient organization:** DARTMOUTH COLLEGE
- **SAM.gov UEI:** EB8ASJBCFER9
- **Principal Investigator:** ELMER R PFEFFERKORN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $195,346
- **Award type:** 5
- **Project period:** 1981-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125652

## Citation

> US National Institutes of Health, RePORTER application 3125652, TOXOPLASMA GONDII:  CELL BIOLOGY AND GENETICS (5R01AI014151-11). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3125652. Licensed CC0.

---

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