MELANOGENESIS IN CRYPTOCOCCUS NEOFORMANS

Project: Research project

Project Details

Description

Melanin synthesis has been associated with virulence for a variety of
microbial pathogens. However, little is known about either
melanogenesis or the structure of melanin. The experimental system that
Dr. Nosanchuk will study is that of Cryptococcus neoformans, a
pathogenic fungus which causes life-threatening meningitis in 5-10
percent of patients with AIDS. This system has several unique advantages
for the study of melanin and virulence, including the fact that
melanized and non-melanized cells can be easily generated by simply
growing the organism with or without a variety of phenoloxidase
substrates. In addition, melanogenesis in C. neoformans is catalyzed by
a single enzyme. Dr. Nosanchuk proposes a novel approach to the study
of melanin and melanogenesis C. neoformans by applying the technology
of phage display libraries to identify melanin-binding peptides that
will comprise unique reagents for the study of melanin. Furthermore,
murine monoclonal antibodies (mAbs) will be generated that bind melanin.
Melanin-binding peptides and mAbs will be used to study melanization in
vitro and in vivo. The objectives are to determine whether melanogenesis
occurs in vivo and to obtain information on the structure of melanin.
Four specific aims are proposed: 1. To identify peptides which bind
melanin; 2. To study the antibody response to melanin and generate
melanin-binding mAbs; 3. To explore the structure of melanin using
biochemistry, phage display peptide libraries and mAbs; and 4. To use
peptides and mAbs to study C. neoformans melanogenesis in vivo and in
vitro.
StatusFinished
Effective start/end date7/1/986/30/99

Funding

  • National Institute of Allergy and Infectious Diseases

ASJC

  • Applied Microbiology and Biotechnology
  • Library and Information Sciences
  • Biochemistry
  • Biotechnology
  • Microbiology

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