Impact:

This innovative research will yield information about transmission, pathogenesis and intervention strategies to enable detection, control and eradication of new emergent diseases.

Component 2:  Genetic and Biological Determinants of Disease Susceptibility

Problem Statement 2A:  Mastitis

Outputs:

·        Identify genetic variations associated with difference in immune cell activation, migration, and host responses to Gram-positive versus Gram-negative bacteria.

·        Effective vaccines to prevent mastitis.

·        New biotherapeutic platforms based on protective host proteins to induce the cow’s innate immune response.

·        Therapeutics to reduce cell damage during mastitis.

·        Markers for mammary stem cells and methods for their regulation.

·        New biotherapeutic platforms based on targeted expression of host-derived inflammatory products with receptor antagonists and/or siRNA molecules.

·        Innovative approaches using naturally expressed anti-bacterial peptides to increase resistance to prevalent pathogens.

·        New management and nutritional schemes to prevent metabolic stresses contributing to immunosuppressive states in the dairy cow.

Impact:

The development of new genomics- and immunologic-based strategies will provide dairy farmers with new and effective options for controlling mastitis.

Component 2:  Genetic and Biological Determinants of Disease Susceptibility

Problem Statement 2B:  Avian Tumor Viruses

Outputs:

·        Basic research information to understand how genetic variations influence the immune response to Marek’s disease infection.

·        Basic research information to understand how the interplay between specific host and Marek’s disease viral genes, and the variation within these genes, leads to disease susceptibility or resistance.

·        Simple molecular tests to pathotype field strains of Marek’s disease virus.

·        Identification of viral genes responsible for pathogenesis and identification of predictors of virulence shifts.

·        Elucidation of viral genes associated with immune evasion mechanisms.

·        Characterization of biological pathways that lead to the development of Marek’s disease.

·        Characterization of vaccine-induced determinants of protective immunity.

·        A safe and highly effective vaccine with mass vaccination capability that conveys protection against emerging Marek’s disease viral strains in defined host animal genotypes.

Impact:

The availability of genomic-based countermeasures will provide new synergistic options that can be used strategically by the poultry industry to design effective control programs against emerging Marek’s disease viral strains.

Component 2:  Genetic and Biological Determinants of Disease Susceptibility

Problem Statement 2C:  Mucosal Diseases of Livestock and Poultry

Outputs:

·        Discovery of genes that confer susceptibility to mucosal diseases of cattle, pigs, and poultry.

·        Identification of genomic regions or specific structural variations that are associated with differences in pest- and disease-resistance traits.

·        Improved methods of predicting genetic merit based on dense SNP-based marker data.

·        Development of enabling tools (immunological reagents, SNP markers and SNP Haplotypes) to propel our understanding of host responses to mucosal diseases.

·        Identification of the genes mediating resistance from previously determined quantitative trait loci (QTL) associated with susceptibility to mucosal diseases of livestock and poultry.

·        Differences in host immunological and physiological responses to mucosal diseases will be associated with genetic markers and then fine-mapped to specific genes.

·        Gene expression and genetic variations associated with protective mucosal immune responses will be identified and characterized.

·        Biological determinants of innate and adaptive protective immunity will be identified and characterized.

·        Comparative genetic maps to identify areas of similarity (synteny) between the bovine, swine, avian, humans, and mice genome.

·        Identification of markers for the detection of underlying mucosal disease infections.

·        Highly effective diagnostics, vaccines, and biotherapeutics designed to prevent and control mucosal diseases in targeted animal populations.

Impact:

·        The ability to identify animals susceptible to mucosal pathogens likely to be encountered in defined production systems will enhance our ability to improve farm biosecurity measures and the management of diseases.

·        Animal genomics research will make important contributions to our understanding of developmental biology and advance human and veterinary biomedical research.

·        Comparative animal genomics will provide new venues for understanding animal and human host responses to zoonotic diseases.

·        Farm animal functional genomics will provide new research platforms for understanding wildlife diseases.

·        Animal genomics will provide the tools to align animal health traits with targeted production environment to increase their performance in intensive or extensive management systems.

·        Animal genomics will provide new technologies to enhance marker assisted selection of disease resistance traits.

·        Animal genomics will provide new genomics-based diagnostic tools for managing disease susceptibility traits at the farm level.

·        Targeted disease resistance to reduce mucosal infectious diseases will lessen the use of chemicals and drugs to control animal disease in the farm environment.

·        Genetic markers will enhance traceability and on-farm biosecurity.

·        Enhance the ability to breed animals for selected traits that confer health and environmental sustainability in target management production system.

·        Animal genomics will enable the design of highly effective diagnostics, vaccines, and biotherapeutics to prevent and control mucosal diseases in targeted animal populations.   

Component 3:  Countermeasures to Prevent and Control Zoonotic Diseases

Problem Statement 3A:  Brucellosis

·        Scientific information to increase our understanding of immunologic responses in bison, elk, and feral swine, including mechanisms of persistent infections, host tolerance, and protective immunity.

·        The development of a safe and efficacious brucellosis vaccine for bison that can be remotely delivered.

·        New vaccine platforms designed to control and eradicate brucellosis in elk.

·        New vaccine platforms designed to control and eradicate brucellosis in feral swine.

·        New diagnostic platforms with improved sensitivity and specificity profiles to facilitate the diagnosis and epidemiologic trace back of Brucella strains in field outbreaks.

Impact:

The discovery of new countermeasures specifically designed to prevent and control brucellosis in wildlife will eliminate new source of infections and enable the eradication of brucellosis in our domestic livestock.

Component 3:  Countermeasures to Prevent and Control Zoonotic Diseases

Problem Statement 3B:  Leptospirosis

Outputs:

·        In vitro disease models consisting of host cell cultures leading to molecular characterization of host-bacterial interactions, variations in gene expression, and associated pathogenic mechanisms.

·        Characterization of protective immune responses to spirochete antigens in large and small animal disease models.

·        Large-scale sequence analysis to characterize the genome of selected spirochetes and identify strain specific regions in various Leptospira strains.

·        Multi-locus sequencing to determine genetic variability of key genes.

·        Transcription studies to identify differentially expressed genes to characterize virulence traits and select vaccine candidates.

·        Genetically altered bacteria using in vitro and in vivo studies to establish key links between specific genes and phenotype.

·        Discovery of efficacious molecular vaccines to prevent the spread of Leptospirosis in domestic animals and wildlife.

Impact:

·        Functional genomics analysis of Leptospira strains will enable the identification of virulence determinants, vaccine discovery research, and new diagnostic platforms for classification of field strains.

·        New generation vaccines will improve the control of maintenance and accidental host infections in our domestic animals thereby lowering the incidence of disease and protecting farm workers from spirochete-associated zoonoses. 

Component 3:  Countermeasures to Prevent and Control Zoonotic Diseases

Problem Statement 3C:  Tuberculosis

Outputs:

·        Identification of microbial immunogens critical for development of protective immunity.

·        Scientific information to increase our understanding of the molecular pathogenesis of Mycobacterium bovis infections.

·        Comparative analyses to understand the variations of host immune responses to natural infections versus vaccination as well as neonatal versus adult cattle responses

·        Discover improved sensitive and specific diagnostic platforms amenable to the rapid screening of large cattle herds.

·        Discover diagnostic platforms to differentiate infected versus vaccinated animals.

·        Discover effective vaccine platforms to prevent and control Mycobacterium bovis in cattle and relevant wildlife reservoir hosts.

Impact:

New improved countermeasures to control Mycobacterium bovis in wildlife and domestic livestock will help prevent new incidences of bovine tuberculosis and support its eradication from the United States. 

Component 4:  Countermeasures to Prevent and Control Respiratory Diseases

Problem Statement 4A:  Ruminant Respiratory Diseases

Outputs:

·        Define determinants of virulence and characterize mechanisms of infection.

·        Define pathogen interactions that lead to polymicrobial infections and respiratory disease complexes.

·         Characterize mechanisms of immune evasion and protective immunity.

·         Develop drug and vaccine delivery systems that target the ruminant respiratory tract.

·        Discover and evaluate alternatives to antibiotics for preventing and treating respiratory diseases.

·        Discover diagnostic platforms that can be used to develop on-site tests.

·        Discover highly effective vaccines that induce targeted immune responses to prevent colonization of the respiratory tract and prevent shedding and disease transmission.

Impact:

The overall impact of the research will be improved diagnosis, control, and prevention of endemic respiratory diseases that will benefit the beef industry. The impact of the research will be derived from the identification of disease pathogen reservoirs, understanding pathogen transmission, and the discovery and technology transfer of highly effective diagnostics, vaccines, and biotherapeutics designed to control and eradicate respiratory diseases from herds.  Incremental development of these tools will provide more predictable costs and better potential returns to cattle and sheep producers, making the business of livestock production sustainable.  The overall goal of these projects is to produce scientific information and tools that will enable the U.S beef industry to remain competitive and profitable.

Component 4:  Countermeasures to Prevent and Control Respiratory Diseases

Problem Statement 4B:  Porcine Respiratory Diseases

Outputs:

·        Define pathogen interactions that lead to polymicrobial infections and respiratory disease complexes in swine.

·        Characterize the changes in gene expression underlying porcine cellular responses to infection with respiratory pathogens.

·        Characterize global changes in gene expression of porcine bacterial pathogens in response to respiratory infection.

·        Define determinants of virulence and characterize mechanisms of infection.

·        Genomic and proteomic analysis of respiratory pathogen to determine changes in gene expression during the infection process.

·        Identification of microbial genetic variations associated with differences in virulence and disease transmission.

·         Characterize mechanisms of immune evasion and protective immunity.

·        Discover highly effective vaccines that induce targeted immune responses to prevent colonization of the respiratory tract and prevent shedding and disease transmission.

Impact:

The overall impact of the research will be improved control and prevention of endemic respiratory diseases that will benefit the swine industry.  The impact of the research will be derived from better understanding the pathogenesis of disease and the discovery and technology transfer of control measures, including vaccines, designed to eradicate respiratory diseases from swine herds.  The overall goal of these projects is to produce scientific information and tools that will enable the U.S swine industry to remain competitive and profitable.

Component 4:  Countermeasures to Prevent and Control Respiratory Diseases

Problem Statement 4C:  Poultry Respiratory Diseases

Outputs:

·        Define the characteristics of aerosol spread for priority respiratory pathogens in relevant poultry production systems.

·        Define determinants of virulence and characterize mechanisms of infection.

·        Define pathogen interactions that lead to polymicrobial infections and respiratory disease complexes.

·         Characterize mechanisms of immune evasion and protective immunity.

·         Develop drug and vaccine delivery systems that target the avian respiratory tract.

·        Discover and evaluate alternatives to antibiotics for preventing and treating respiratory diseases.

·        Discover differential diagnostics platforms that can be used to develop flock-side tests

·        Discover highly effective vaccines that induce targeted immune responses to prevent colonization of the respiratory tract and prevent shedding and disease transmission.

Impact:

The overall impact of the research will be improved diagnosis, control, and prevention of endemic respiratory diseases that will benefit the poultry industry. The impact of the research will be derived from the identification of disease pathogen reservoirs, understanding pathogen transmission, and the discovery and technology transfer of highly effective diagnostics, vaccines, and biotherapeutics designed to control and eradicate respiratory diseases from poultry flocks.  The overall goal of these projects is to produce scientific information and tools that will enable the U.S poultry industry to remain competitive and profitable.

Component 5:  Countermeasures to Prevent and Control Reproductive and Neonatal Diseases

Problem Statement 5A:  Bovine Viral Diarrhea (BVD)

Outputs:

·        Discovery of methods to diagnose cattle pregnant with persistently infected fetuses.

·        Discovery of effective diagnostics, vaccines, and biotherapeutics to support reproductive health management protocols.

Impact:

Results of this research will provide improved diagnostic tests, vaccines and scientific information to elucidate the causes of persistently infected ruminants with BVDV.  Results of this research will also provide new information on how certain viruses (e.g., pestiviruses) are able to attack the host immune system, thus enabling science-based strategies for vaccine or biotherapeutic intervention.  This research will provide countermeasures and integrated protocols to enable eradication or more effective prevention of BVDV in U.S. cattle herds.   

Component 5:  Countermeasures to Prevent and Control Reproductive and Neonatal Diseases

Problem Statement 5B:  Neosporosis

Outputs:

Component 5:  Countermeasures to Prevent and Control Reproductive and Neonatal Diseases

Problem Statement 5C:  Reproductive Health of the Dairy Cow

Outputs:

·        Scientific information to determine the role of infectious and metabolic diseases that result in decreased reproductive performance.

·        Scientific information to define immune mechanisms involved in reproductive failure.

·        Discovery of genetic and phenotypic markers that influence fertility.

·        Development of diagnostics to enable marker-assisted selection programs.

·        Development of management tools to prevent infectious and metabolic diseases that affect reproductive efficiency.

·        Discovery of effective diagnostics, vaccines, and biotherapeutics to support reproductive health management protocols.

Impact:

Results of this research work will provide scientific information to elucidate the causes of reproductive diseases and provide countermeasures and integrated protocols to increase the overall reproductive performance of U.S dairy herds.   

Component 6:  Countermeasures to Prevent and Control Enteric Diseases

Problem Statement 6A:  Johne’s Disease

Outputs:

·        Comparative analyses of the M. paratuberculosis proteome leading to the development of highly sensitive and specific diagnostic tests for detection of M. paratuberculosis  for cattle and sheep through identification and characterization of unique bacterial genes and proteins

·        Host immune response analyses to understand the mechanisms of control in early stages of disease and the switch in immunity that results in progression from subclinical to clinical disease.

·        Highly effective vaccine platform that prevents subclinical disease, shedding of M. paratuberculosis, and progression to clinical disease.

Impact:

These studies will provide information on key host-pathogen responses during the infection process leading to the development and application of genomic-based diagnostic tests and vaccines to prevent and control Johne’s disease.

Component 6:  Countermeasures to Prevent and Control Enteric Diseases

Problem Statement 6B:  Enteric Diseases of Poultry

Outputs:

·        Determine and quantify factors associated with disease risk.

·        Determine modulators of stress in production systems that affect enteric disease development.

·        Discovery of cytokines and their expression profiles that govern processes involved in host defense during enteric infection.

·        Identify and characterize pathogens responsible for poultry enteric disease complexes.

·        Develop pathogen-specific markers useful for molecular or immunological detection.

·        Develop molecular tools to study the epidemiology and ecology of enteric pathogens.

·        Discover strategies that enhance the clearance of enteric pathogens.

·        Discover immune epitope candidates for the successful development of vaccine strategies.

·        Discover immunointervention strategies that prevent the development of enteric infections.

Impact:

·        Ability to detect pathogens responsible for enteric disease complexes.

·        Understand the relationship of enteric pathogens to each other and host co-evolution.

·        Discovery of tools that enable the prevention and control of enteric diseases.

Component 7:  Countermeasures to Prevent and Control Parasitic Diseases

Problem Statement 7A:  Drug Resistant Gastrointestinal (GI) Parasitic Diseases

Outputs:

·        Develop molecular-based techniques to rapidly speciate and quantify Eimeria oocysts in litter samples.

·        Develop rapid tests to identify drug resistance markers in Eimeria field isolates.

·        Discover recombinant vaccines that are safe and effective against heterologous field challenges with mass vaccination capability to prevent outbreaks of coccidiosis in poultry farms.

·        Investigate and document drug resistance related to parasite species; e.g., Haemonchus contortus, H. placei, Cooperia punctata, C. oncophora, Ostertagia ostergii, Nematodirus helvetianus, and trichostrongyles.

·        Determine the effect of different production and management systems on the manifestation of drug resistance in sheep, dairy, cow-calf, and feedlot operations.

·        Identify molecular probes to better define parasite species in the field.

·        Identify molecular markers of drug resistance based on mode of action and measure the allele frequency of parasite genes involved in drug resistance.

·        Identify patterns of gene flow in nematode populations to manage drug resistance in different production systems to reduce the impact of drug resistance on productivity.

Impact:

·        A greater understanding of the extent and type of drug resistance in nematodes of U.S. cattle and sheep, especially as related to the type and phase of farm management.

·        Improved molecular probes for speciating nematodes in the farm environment, and for identifying markers of drug resistance.

·        Reduction in the incidence and effects of nematode infections in cattle and sheep by allowing fact-based application of appropriate anti-helminthic compounds.

Component 7:  Countermeasures to Prevent and Control Parasitic Diseases

Problem Statement 7B:  Hemoparasitic Diseases

Outputs:

Component 8:  Countermeasures to Prevent and Control Transmissible Spongiform Encephalopathies

Scrapie

Chronic Wasting Disease (CWD)

Bovine Spongiform Encephalopathy (BSE)

Outputs:

• Develop sensitive and specific ante-mortem tests that are rapid and scaleable.
• Determine the presence of TSE strains and unusual isomers of the prion protein and establish their biochemical, pathological, and epidemiological profile.
• Determine the pathogenesis of TSEs, including establishing route(s) of prion migration in the host, amplification of the agent, and disease expression.
• Conduct interspecies transmission studies to determine the host range specificity and resulting risk of TSEs to other animal species.
• Develop enhanced rapid methods of agent detection to protect the human environment.
• Develop cost effective methods of inactivating TSE agents.
• Identify and characterize genotypic variations and functional genomic mechanisms associated with disease susceptibility or resistance.

Impact:

• Scientific information will enable regulatory and action agencies to promulgate science-based regulatory policies.
• The development of countermeasures will enhance current control and eradication programs for Scrapie and CWD and enable the prevention and containment of future occurrences of BSE worldwide.