This $749,594 Project Grant award from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) supports research to investigate the role of the host sphingosine kinase 1 (SK1) pathway in controlling Cryptococcus neoformans (CN) fungal infection during immunodeficiency. The research aims to determine the immune mechanisms by which the SK1-S1P pathway regulates the organization of CN granulomas, and define the immune response that protects...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $515,875 to support research on the mechanisms by which the fungus Cryptococcus neoformans induces meningoencephalitis and neurotoxicity in immunocompromised individuals, particularly those with HIV/AIDS. The key objectives are to: 1) Determine how the Cryptococcus polysaccharide capsule component glucuronoxylomannan...
This $1,148,123 Project Grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) supports research to understand the molecular processes and pathways governing the maturation, germination, and pathogenesis of Cryptococcus spores. The primary objectives are to: 1) Determine the molecular mechanisms of spore germination, 2) Identify factors that promote spore germination competence, and 3) Evaluate...
This $300,000 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) aims to develop an anti-Candida peptide vaccine that can reduce the burden and morbidity of life-threatening disseminated candidiasis. The funding supports the use of a novel liposome-displayed peptide vaccine approach, utilizing FBA and MET6 peptide immunogens that have shown promise in inducing protective antibodies...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research Program (CFDA 93.855), provides $170,000.00 in funding to Prokaryotics Incorporated to conduct research on developing new antifungal treatments. The key objectives of this research project are to: 1) use cryo-electron microscopy to elucidate the molecular structures of the fungal target enzyme MCD4 and its human ortholog PIG-N, both in apo and...
This project grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $642,775 to the University of California, Davis to develop novel antifungal agents. The research will leverage one-bead one-compound (OBOC) combinatorial technology and screening strategies to rapidly identify and optimize membrane-active antifungal peptides with desired physiochemical properties, broad-spectrum...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $494,696 to The University of Texas Health Science Center at San Antonio (UTHSCSA) to conduct research on translational control mechanisms that regulate the ability of the fungal pathogen Candida albicans to respond to host environmental stresses and undergo morphological changes associated with virulence. The research...
This federal Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), aims to discover and develop new therapeutic approaches more potent than current antifungals for the treatment of invasive fungal infections such as cryptococcosis, candidiasis, and aspergillosis. The $300,000 award to Microrid Technologies Inc. will fund research to screen chemical libraries and identify potent...
This Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), provides $232,073 to investigate the host-pathogen dynamics between the fungal pathogen Cryptococcus neoformans (CN) and HIV co-infection in microglia. The overarching goal is to explore the phenomenon of replicative aging in CN and its impact on the survival of aged CN cells in the cerebrospinal fluid of AIDS patients. The...
This $2,760,350 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID), under the Allergy and Infectious Diseases Research program (CFDA 93.855), will support research to elucidate fundamental pathways governing the host's ability to combat Cryptosporidium parvum (C. parvum) infections at mucosal sites. The key objectives are to establish reliable small mouse models of cryptosporidiosis and unravel the intricacies of interferon-gamma (IFN-g) responses during...
AN EXTRACELLULAR VESICLE COMPONENT AS A CANDIDATE TO CONTROL CRYPTOCOCCOSIS. - AN EXTRACELLULAR VESICLE COMPONENT AS A CANDIDATE TO CONTROL CRYPTOCOCCOSIS. SUMMARY FUNGAL DISEASES ARE A MAJOR THREAT TO IMMUNOCOMPROMISED PATIENTS. CRYPTOCOCCOSIS, CAUSED BY MEMBERS OF THE CRYPTOCOCCUS GENUS, IS RESPONSIBLE FOR NEARLY 200,000 DEATHS WORLDWIDE ANNUALLY. IMMUNOCOMPROMISED INDIVIDUALS ARE THE PRIMARY POPULATION THAT DEVELOP CRYPTOCOCCAL MENINGOENCEPHALITIS, A 100% FATAL CONDITION IF LEFT UNTREATED. C. NEOFORMANS, THE MOST COMMON CAUSATIVE AGENT OF CRYPTOCOCCOSIS, HAS RECENTLY BEEN CLASSIFIED AS A CRITICAL THREAT BY THE WORLD HEALTH ORGANIZATION. DESPITE THEIR DEVASTATING IMPACT ON HUMAN HEALTH, FUNGAL DISEASES HAVE BEEN CONSISTENTLY NEGLECTED, AS DEMONSTRATED BY THE LACK OF AVAILABLE ANTIFUNGAL VACCINES AND OUR LIMITED ANTIFUNGAL ARMAMENTARIUM. THE RODRIGUES AND NOSANCHUK LABORATORIES HAVE COLLABORATED ACTIVELY FOR OVER 15 YEARS IN THE FIELD OF FUNGAL INFECTIONS AND HAVE EXTENSIVELY CHARACTERIZED FUNGAL EXTRACELLULAR VESICLES (EVS) IN VARIOUS MODELS. EVS PLAY CRUCIAL ROLES IN FUNGAL PHYSIOLOGY AND PATHOGENESIS. RECENTLY, WE DISCOVERED THAT THE TRIPEPTIDE ISOLEUCINE-PROLINE-ISOLEUCINE (IPI), A SMALL MOLECULE COMPONENT OF EVS, EFFECTIVELY CONTROLS CRYPTOCOCCAL INFECTION IN AN INVERTEBRATE HOST. IPI ACTS AS AN INHIBITOR OF DIPEPTIDYL PEPTIDASE 4 (DPP4), WHICH PLAYS A ROLE IN FUNGAL PATHOGENESIS, AS WELL AS IN HOST PHYSIOLOGY, BY REGULATING INSULIN AND GLUCOSE. IN THIS PROPOSAL, WE AIM TO INVESTIGATE THE PARTICIPATION OF IPI AND DPP4 IN FUNGAL IMMUNOPATHOGENESIS THROUGH THREE SPECIFIC AIMS. AIM 1 WILL EXPLORE THE PROTECTIVE MECHANISMS OF IPI IN ANIMAL MODELS OF CRYPTOCOCCOSIS. AIM 2 FOCUSES ON UNDERSTANDING THE ROLES OF FUNGAL AND HOST DPP4 IN DISEASE PROGRESSION, INCLUDING THEIR IMPACT ON GLUCOSE METABOLISM AND THE IMMUNE RESPONSE. AIM 3 SEEKS TO DETERMINE THE RELEVANCE OF IPI AND DPP4 IN OTHER FUNGAL MODELS. SUCCESSFUL COMPLETION OF THIS PROJECT WILL PROVIDE A COMPREHENSIVE CHARACTERIZATION OF A NOVEL CANDIDATE FOR COMBATING CRYPTOCOCCOSIS AND PERHAPS OTHER DISEASES. FURTHERMORE, WE ANTICIPATE GAINING INSIGHTS INTO THE CONNECTION BETWEEN DPP4 AND FUNGAL PATHOGENESIS. THIS PROPOSAL AIMS TO FOSTER INTERCONTINENTAL COLLABORATION AND ENHANCE THE CAPABILITIES OF FIOCRUZ, THE BRAZILIAN INSTITUTION LEADING THIS COLLABORATIVE EFFORT.