P01AI181898

Systems genetics of tuberculosis - Systems genetics of tuberculosis.

Overall program abstract: Mycobacterium tuberculosis (MTB) infection outcomes are highly variable.

Most individuals contain the infection and remain asymptomatic for a lifetime.

A fraction of those infected develop disease; and even among these patients, the timing, location, and presentation of the pathology is remarkably diverse.

This variability is also evident in the efficacy of both chemotherapy and vaccination.

While this heterogeneity represents a great challenge for TB control efforts, the biological determinants of MTB infection outcome have been difficult to define due to the complexity of contributing factors.

Both human and bacterial populations are genetically and phenotypically diverse, and interactions between this genetic complexity and a variety of environmental factors ultimately determines clinical course.

To overcome this complexity, we leveraged new mammalian and bacterial genetic resources to create a model system that can be used to study the effect of each of these variables in isolation and in combination.

Host diversity is incorporated using mice from the Collaborative Cross (CC) and Diversity Outbred (DO) resources, newly generated reference panels that reflect the diversity of an outbred population.

Bacterial variation is incorporated using large panels of MTB strains that reflect both naturally- and experimentally-generated diversity.

Controlled interventions, such as vaccination, can be overlaid on this host-pathogen diversity.

Using this highly-tractable system, our program discovered that the combinatorial complexity of these interactions converge on a discrete number of biological pathways that influence outcome.

Supported by the cutting-edge mouse and human genetic, genomic, and analytical resources provided by the cores, our SGTB program will now focus on parallel studies in this model system and human clinical samples to identify and dissect the pathways that influence outcome.

This structure will ensure that mechanistic mouse studies are linked to relevant human phenotypes.

Ultimately, these insights will be leveraged to develop more precise correlates of risk, more specific diagnostics based on clinical phenotypes, and new strategies for the optimization and preclinical development of vaccines.

University Of Massachusetts Medical School

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Worcester, Massachusetts 01655 United States

Single Zip Code

NIAID Investigator Initiated Program Project Applications (P01 Clinical Trial Not Allowed) (PAR-22-225)

Amendment Since initial award the total obligations have increased 95% from $2,817,044 to $5,499,526.