项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

LOVE, DONA

项目受资助机构

JOHNS HOPKINS UNIVERSITY

项目编号

5R01AI052733-16

立项年度

2019

立项时间

未公开

研究期限

未知 / 未知

项目级别

国家级

受资助金额

533349.00美元

学科

Infectious Diseases

学科代码

未公开

基金类别

Non-SBIR/STTR RPGs

关键词

未公开

参与者

CASADEVALL, ARTURO

参与机构

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

项目标书摘要：? DESCRIPTION (provided by applicant): Melanin is a pigment that performs a variety of functions and is found in the plant and animal kingdoms. In fungi melanin reinforces cell walls, shields against ultraviolet radiation as well as toxic metals, harnesses high energy electromagnetic radiation and contributes to virulence. Despite its importance, very little is known about the structure of melanin because it is insoluble and amorphous, making it difficult to analyze. In the previous funding period we described a new, melanin-based process for harnessing energy through the capture of radiation; we laid the foundation for a new melanoma therapy targeting melanin that is now in clinical trials; we demonstrated the remarkable ability of melanin to shield against radiation and provided a novel way to study the structure of melanin by solid-state NMR analysis; we discovered an extracellular vesicular transport in fungi (associated with the formation of a fungal melanosome). This research program renewal is focused on melanization in the human pathogenic fungus Cryptococcus neoformans, which is responsible for almost a million annual cases of meningitis worldwide, primarily in patients with AIDS. We will build on the achievements and tools of the previous funding period in order to focus on the fungal melanosome and the process of melanization. Three Specific Aims are proposed: 1) To generate a molecular definition for the cargo in melanizing vesicle populations; 2) To investigate the mechanism by which the fungal melanosome interacts with the cell wall; 3) To investigate the molecular structure of C. neoformans melanin assemblies on their cell-wall scaffold. C. neoformans melanin is critical for virulence and it is also a potential target for therapeutic drug development. Agents that target melanin are attractive because they could be applied against a broad array of pathogenic fungi.