Duration: 10/01/2003 to 09/30/2008

Administrative Advisor(s):

NIFA Reps:

Non-Technical Summary

Statement of Issues and Justification

STATEMENT OF THE ISSUE

Disease losses represent a significant component in the overall cost of poultry production. These costs not only include the direct losses due to increased mortality and condemnations but also increased production costs caused by suboptimal food conversion, cost of vaccines and vaccination. Several pathogens, e.g., chicken infectious anemia virus (CIAV), may cause subclinical infections that interfere with protective immune responses to other pathogens. In some cases, pathogens are in a continuing arms race with vaccines and genetic resistance in becoming more pathogenic as was eloquently described by Witter (2001) for Mareks disease. In order to battle these pathogens it will be essential to increase our understanding of the genetic bases for disease resistance and immunity, which will lead to more effective prevention and treatment procedures. These new methods will increase production efficiency and lower costs.

JUSTIFICATION

World-wide consumption of poultry products has increased drastically during the last 25 years and is expected to increase over the next decade (Roenigk, 1999). Poultry consumption rose world-wide from 31.1 million metric tons in 1988-1990 to an estimated 55 million metric tons in 1998-2000, which represents a 77% increase. Equally impressive is the increase in poultry consumption during this period from 21.8 to 29.0 % as the share of poultry, pork, and beef-veal consumption. It is expected that the shift towards poultry consumption will continue (USDA, 1997 and 1998). The continuing increase in poultry production has important economic consequences for the USA. First, the USA has one of the most efficient poultry production systems in the world and is currently an exporter of poultry products. Broiler exports in 1996 were 2.07 x 106 metric tons with a value of $2,027 x 106, (Broiler Industry 60 (5):22, May, 1997) which represented a 20.8% increase over 1995. Further growth in the production of broilers is expected and it is anticipated that the USA poultry producers will profit from increased worldwide demand. In addition, the production of poultry feed is also in a large part dependent on the USA grain and soya production, providing additional benefits to the economy. Although these predictions may have been overly optimistic in view of the current economical situation, poultry production in the USA remains strong. Broiler placements in the USA totaled 7.23 billion in the first 10 months of 2002 (WATT Global e-NEWS, October 26, 2002).

The impact of diseases is one major impediment for increased productivity. Total losses caused by specific diseases not only include mortality, decreased egg production, and condemnations but also costs of vaccination, chemotherapy, and eradication programs. Although there are no recent published data available on these losses, Biggs (1982) quoted a loss of $1,427 x 106 in 1975 for the US alone. Witter and Schat (2002) estimated that the total losses (mortality, vaccination costs, reduced egg production) caused by Mareks disease (MD) were close to one billion dollars worldwide in 1984. These losses have certainly increased over the last 17 years, especially given the emergence of ever more virulent strains of MDV. These so-called vv+MDV strains are causing MD outbreaks in chickens properly vaccinated with MDV (Witter, 2001). Recent problems with Salmonella enteriditis have caused considerable economic losses and further losses can be expected. For example, if FDA suggestions for S. enteriditis elimination are implemented, the costs of table eggs will increase dramatically (Dr. D. Kradel, personal communication). The losses due to S. enteriditis in the US are based on the human health impact of only a small number of positive hens. In addition to the clearly identifiable problems, a substantial portion of the losses is caused by suboptimal production as a consequence of interactions among management, genetic resistance and disease agents (Biggs, 1982).

Reduction of these losses depends on several interrelated factors; the interaction between genetic background of the chicken and the development of the immune responsiveness is especially relevant. Immune responsiveness is at least in part determined by the major histocompatibility complex (MHC) as well as by other genetic traits. The collaborating NE-60 stations have demonstrated MHC-related resistance to a number of diseases. Information demonstrating that genetic selection related to immunity may reduce economical losses is important, because successful adaptation of appropriate selection procedures by primary breeders may lead to a rapid dissemination of more resistant strains and a subsequent reduction in losses. NE-60 has invited representatives of breeder organizations to the annual meetings to disseminate new information on an informal basis. These breeder representatives also bring information on field problems and comments on the importance of approaches taken by NE-60. These aspects will become even more important with the advent of biotechnology applications especially because the chicken genome will be sequenced during the next five years.

At this time, the sequence of the MHC related genes is already available (Kaufman et al, 1999). These data will be important toward development of tailored vaccines presenting epitopes that are recognized by specific haplotypes. ARS-ADOL station has already shown that certain genetic strains respond differently to different MD vaccines. Recent data from the NYC station have shown which specific gene products are recognized in cell-mediated immune responses. The combined data from these groups indicate that tailored vaccines may become a distinct possibility in the future and research towards this goal is included in this proposal. Similarly, several NE-60 groups are working on the regulation of immune responses by studying cytokine activation pathways that are important for innate and acquired immune response.

In the previous five-year project outline it was stated that rapid progress in the understanding of the interactions between genetic background and disease resistance was expected over the next 5 to 10 years. This prediction was based, in part, on the development of MHC-congenic strains and the development of monoclonal antibodies (Mabs) for lymphocyte (sub)populations by several participating stations of NE-60. During the last five years, we have also made strong progress in the molecular aspects of genetic resistance to diseases by cloning several cytokine genes (e.g., ARS-PBESL) and examining the expression patterns of these cytokines using quantitative real-time PCR assays (several NE-60 stations). The combination of these new and previously developed tools have led to a very productive first 4 years of the current grant with 267 papers published and additional papers in press both of which include a substantial number of joint publications among NE-60 stations (Publications list).

Further progress in improving genetic resistance to diseases will require the application of advanced techniques in immunology, biochemistry, virology, bacteriology, parasitology, molecular biology and genetics to study pathogens using well-defined strains of chickens in facilities designed to contain infectious agents. NE-60 members form the ideal team to pursue the proposed studies, because they have: i) a proven collaborative research record, and ii) as a group the needed expertise listed above.

Related, Current and Previous Work

RELATED CURRENT AND PREVIOUS WORK

Extensive publication searches indexed in the comprehensive databases (Agricola, Biosis, CAB, CRIS, Health Index, and Medline) for the last five year period revealed substantial scientific contributions that NE-60 members have made in genetics of disease resistance and immune response in poultry. The truly essential, cooperative, multidisciplinary nature of the project is illustrated by the many joint-authored publications among participating stations. Other groups outside the U.S. conduct research complimentary to that of NE-60. Institutions in Australia, Czech Republic, Denmark, France, Israel, the Netherlands, and the U.K. conduct research on the chicken MHC. Selection based on non-MHC traits is also performed in the Netherlands, France, and Israel. Marek's disease research programs exist in Japan and the Netherlands. Working relationships, either formal or informal, exist between NE-60 stations and the international laboratories conducting similar research. This assures coordination of efforts and avoidance of unnecessary research duplication. Addition of international contributors from Canada and the Netherlands to the new proposal demonstrates the stature of the project.

The NE-60 project addresses issues in poultry genetics or disease not investgated by other multistate projects related to poultry. Two projects have no emphasis on immunity or disease. NE-127 Biophysical models for poultry production systems studies physiological responses to various environmental factors. Project S-289 "Factors associated with genetic and phenotypic variation in poultry: molecular to populational" focuses on genetic variation in performance traits. The NC-168 project "Advanced technologies for the genetic improvement of poultry" may be the most related to NE-60. Although certain gene families are being examined in both projects, the two efforts remain quite distinct in their objectives and application of work with these genes. The NC-168 project identifies and maps poultry genes while developing strategies for incorporating new genes into selection programs. By contrast, the NE-60 project studies poultry genes to elucidate their role in genetic resistance and immunity. The NRSP-8 National Animal Genome Research Program emphasizes mapping the genomes of various agriculturally important animal species including chickens.

Several stations (CA, DE, IA, NC) as well as collaborators participate on both NC-168 and NE-60 technical committees. This representation will enhance communication to coordinate complementary efforts, encourage appropriate joint efforts and avoid duplication. Other NE-60 members also interact with NC-168. Collaborative efforts between both technical committees are expected to continue. For example, genes important for production traits identified by NC-168 can be evaluated for effects on immunity and disease resistance. Disease resistance genes identified by NE-60 can be examined for their production effects by NC-168. Likewise, lines selected for particular characteristics by NE-60 may be used for NC-168 genome mapping efforts, whereas transgenic chickens or new selection methods developed by NC-168 may be examined for use in immune response and disease resistance studies in NE-60. Two other U.S. laboratories that are NC-168 members conduct poultry genetics research relevant to immunity and disease resistance. OH has studied the genetics of disease resistance in turkeys and the turkey MHC. VA has selected lines for antibody response to SRBC and has used these lines to examine the relationships among blood groups, MHC and disease resistance.

Various laboratories have made progress in elucidating the molecular structure of MHC genes and antigens as well as their sequences. Continued work is needed to define additional polymorphisms, regulation of gene expression and their relationships to disease resistance. Studies of the MHC association with diseases have augmented identification of beneficial alleles for resistance to Marek's disease virus, Rous sarcoma virus, Salmonella enteriditis, and Eimeria species. These diseases represent only a small fraction of the pathogens that can affect poultry so the repertoire of pathogens under study must be expanded. A more detailed understanding of the pathogen-host relationship is also needed. Most studies have utilized genetic stocks of the egg-laying type but this work is now expanding into meat-type birds. All these components of chicken MHC research will be addressed by the proposed studies in this project renewal.

The NE-60 multistate research project scientists design, create, maintain, and study unique poultry genetic lines. Some members carry out all of these functions and others a subset as an integral part of our research. These efforts have been our contribution as well as our responsibility to achieve the project objectives of understanding the genetic basis for immunity to disease. Special genetic lines, established over the last 75 years, are at risk at many research stations. If lost, these unique avian genetic resources (e.g., congenic, recombinant, and inbred lines) are unlikely to be recreated. Since member scientists share these genetic resources in collaborative research, their elimination will impact the project, collaborators as well as the avian research community at large. The Technical Committee recognizes the imperative to conserve the resources currently available. Several Technical Committee members served on the Avian Genetic Resources Task Force and are now part of the National Animal Germplasm Program, Poultry Committee. The members are committed to the establishment of a national system of networked researchers and a site for orphaned stock conservation to support our objectives of understanding and improving resistance to disease in poultry.

Innovative technologies such as candidate gene indentification, applications of recombinant DNA, monoclonal antibodies, DNA probes, and QTL analysis, have been effectively used to identify and characterize many facets of disease resistance or immune function. These techniques expand upon the pioneering work conducted by NE-60 members throughout the project history. Project results continue to be an important and readily applicable in both research and industry. Commercial poultry breeders lead other animal breeders in terms of improvement of a variety of economic traits, including genetic resistance to disease. Further research on new methods to select for disease resistance in poultry must, and will, continue in the NE-60 project. Recent scientific advances in understanding the immune system, and enhanced knowledge about poultry pathogens, promise imminent, significant improvements in poultry health, production efficiency, food safety and animal well-being through genetic selection.

Objectives

1. Characterize the functions of genes and their relationships to disease resistance in poultry with an emphasis on the major histocompatibility complex as well as other genes encoding alloantigens, communication molecules and their receptors.
   
2. Identify and characterize environmental, husbandry, dietary and physiologic factors, and immunosuppressive agents that modulate immune system development, optimal immune function and disease resistance in poultry genetic stocks.
   
3. Develop and evaluate methodologies and reagents to assess immune function and disease resistance to 1) enhance production efficiency through genetic selection in poultry, and 2) identify relationships between genes underlying disease resistance and genes underlying production.
   
4. 
   

Methods

OBJECTIVE 1. Chicken strains characterized for specific genes or features of immune responsiveness remain valuable genetic resources for collaborating NE-60 members and other scientists to evaluate of disease responses. IA will maintain six MHC-congenic lines on the G-B background and 14 other inbred lines of homozygous MHC types including several congenic pairs. NC will maintain lines G-B1, G-B2 and K strain. NH will retain MHC congenic lines including six B complex recombinants. NYC will maintain the SPF flocks of N2a and P2a strains. NYC will develop a small flock free of CIAV DNA. Eight B-congenic lines in inbred line 15I5 are maintained by ARS-ADOL. The station has 19 6C.7 recombinant congenic strains (RCS) containing a different 12.5% of the line 72 genome in the line 63 background. These birds will reveal non-MHC genes affecting tumor resistance and immune development. CA, M. Miller (Beckman Research Institute, BRI) and ARS-ADOL will examine MHC gene expression in the early differentiating embryo using antibodies for B-F, B-L, B-G and Rfp-Y for detection. Cell surface expression will be assayed by indirect immunofluorescence and immuno-PCR. NC will investigate differential iNOS expression in macrophages from hypo- (G-B1 and G-B2) and hyper- (K strain) responder chickens focusing on CD14 and TLRs in LPS-mediated signaling. AL will measure B-FI and B-FIV class I loci transcript expression with real-time PCR. A B-FI molecule transfected cell line will be tested as an NK cell target, to determine if B-FI expression confers resistance to NK mediated killing. AL will identify antigenic peptides of B-FI alleles. B-FI alleles should bind a subset of antigenic peptides due to their low polymorphism and locus-specific sequences compared with the more polymorphic B-FIV molecules. ARS-ADOL and BRI will compare Rfp-Y glycoproteins expression with other class I loci using RP9 cells expressing the Rfp-Y glycoproteins. Avian leukosis virus will be a model system to determine if Rfp-Y presents traditional viral antigens. ARS-ADOL and AL will develop antisera to BFI locus glycoproteins to investigate these molecules. CA will study avian telomere stability and telomerase activity in normal and transformed cell lines. Chicken TERT (telomerase catalytic subunit) will be cloned and transfected to immortalize cells without transformation for research and potential vaccine development. CA and BRI will dissect the gene order of microchromosome 16 focusing on the breakpoints involved in recombinant B haplotypes and the recombinogenic potential of the ribosomal RNA gene complex. Fluorescence in situ hybridization of probes generated at BRI will establish gene order in recombinant haplotypes. IA will define genes controlling response to Salmonella enteritidis (SE) in young chickens. SE vaccine antibody levels and bacterial burden in non-vaccinated chicks after challenge with pathogenic SE will be evaluated. Genes will be assessed in resource populations developed from IA lines and in primary breeder populations. Samples collected before and after SE exposure from birds having differential response to the bacteria will be contrasted with EST slide microarrays (J. Burnside). Larger microarray sets are expected to become available. Real-time PCR measurements for samples will focus on available chicken cytokine genes. Cellular immune studies will measure bacterial phagocytosis and killing, as well as FACS analysis of immune cell surface protein expression. MS will establish the first comprehensive chicken proteomics program that will be a model for agricultural animal species and may be applied to any poultry production problem. Two dimensional polyacrylamide gel electrophoresis, 2-D liquid chromatography electrospray ionization tandem mass spectrometry, mass/charge of whole proteins and peptide sequence will identify differentially expressed proteins in transformed and the non-transformed Marek!&s disease (MD) lymphoma cells. The entire chicken genome sequence will be completed within 12 months. B19 and B21 transformed B cell lines will be used as antigen presenting cells to study genetic resistance to MD. ICP4 and gB MDV antigens will be targeted to the MHC-II antigen presentation pathway. Mass spectrometry will identify antigenic peptides, eluted from the MHC-II molecule binding groove. Synthesized MHC-II tetramers will be loaded with these peptides to study T cell response in MD resistant and MD susceptible birds. Differential gene expression during immune responses will be examined in MDV specific T cells of genetically defined chickens (GUELPH). DE will compare the MD response and specific MHC types in two distinct broiler populations that differ in disease susceptibility. Single nucleotide polymorphisms (SNPs) will be identified in immune-related genes from an F2 broiler population previously challenged with MD. SNPs in the R2-microglobulin and invariant chain genes merit special interest. Non-synonymous SNPs that are more likely to affect the phenotype will be examined. Gene effects on severe stunting in MD challenged birds will be evaluated. NH is developing Rfp-Y congenic chickens on Lines 6.6-2 and UCD 003. Collaborating with BRI, the lines will be tested for Rfp-Y effects on immune responses including Rous sarcoma virus and v-src tumor growth, immunity and metastasis. Regulation of CIAV in gonadal cells will be monitored by CIAV promoter driven reporter gene expression. NYC will transfect cultured theca and granulosa cells with a cloned CIAV promoter/enhancer sequence upstream of the green fluorescent protein gene. Different hormone treatments applied to transfected cells will examine CIAV transcription and replication. NC, NH, CA, and NIU will explore non-MHC alloantigen system effects on immune responses. NH will use stock having L alloantigen alleles on the common genetic background of Line 6.6-2 to examine segregating B and L system types for effects on antibody production as well as other responses. ARS-PBESL will study interleukin receptor molecules in T cell activation with monoclonal antibodies. The station will clone and characterize the IL-2 receptor molecules. ARS-PBESL will investigate various chicken cytokine effects on the intestinal immune system with established protocols. Immunomodulation by cytokines on infection and vaccination against salmonellosis and coccidiosis will be examined. At WAGENINGEN, lines selected for 22 generations for primary antibody responses to SRBC differ in humoral and cellular immunity. F4 (advanced inbred) families will be made to evaluate genomic regions for their contribution to specific and innate immunity. Work will identify positional candidate genes by creating comparative genetic maps for chickens, humans and mice. Bacterial Artificial Chromosome (BAC) libraries will enable the creation of contigs for chromosomal regions containing immune trait genes. The chicken DNA sequence will be crucial to identify these genes for their contribution to immune responses and disease resistance. NC will compare effects of genetic selection on specific immune parameters between modern commercial broilers and the original random-bred control broiler strains. CA will evaluate MD resistance in two ways. Broiler and layer progeny homozygous for the B11 gene will be compared to White Leghorn chicken lines having resistant B21 or susceptible B19 after challenge with the RB1B stain of MD virus. Clinical MD signs plus gross and microscopic MD lesions will be compared to the known resistant and susceptible birds. Inbred parent stocks that are either homozygous or heterozygous for B2 or B5, congenic for background genes, and varied for the Rfp-Y system alleles will be used to study Rfp-Y effects on MD. The genetic background is neither very resistant nor very susceptible to enhance detection of a Rfp-Y influence. Pathogenesis studies will be done as described. OBJECTIVE 2. Multiple stations will study immune enhancement by dietary factors. CA will examine the role of Vitamins A, D, E, and carotenoids in regulating leukocyte development and effector functions. As these fat soluble nutrients are passed from the hen to the chick, the role of the hens diet on the development of the chick will be assessed. NYC will expand studies suggesting that thymulin or dietary manipulations enhance the responsiveness of the specific immune system to vaccination making chickens more resistant to infection. ARS-PBESL will investigate effects of a Lactobacillus-based probiotic on intestinal intraepithelial lymphocytes subpopulations in broiler chickens, and its potential protection against a coccidial challenge. FRAMINGHAM will examine mannanoligosaccharide!&s effectiveness as an immunomodulator in cooperation with other NE-60 stations. AR will study immunomodulatory effects of dietary supplements in broilers. (deleted) NC will study ontogeny of mucosal immunocompetence influenced by genetics and nutrition. CA will explore how genetic differences in immunocompetence affect nutrient needs. The station will determine energetic substrate costs of the immune response and appropriate dietary adjustments for optimizing the responses. ARS-PBESL will evaluate CpG ODNs and other immunostimulants on the development of intestinal immune system with in vitro and in vivo studies. The station has identified a CpG motif that stimulates chicken macrophage production of NO and IL-6. The CpG-ODNs potential as a vaccine adjuvant will be evaluated against salmonellosis and coccidiosis. NYC will further develop the IBV infection disease model to study thymulin supplementation effects on enhancing innate immunity to viral infection. Studies will elucidate the intracellular pathways stimulated by either thymulin or dietary manipulations that enhance NK cell activity. NC will define the role of PEMS-associated astrovirus and reovirus using combination challenges of poults with astrovirus, reoviruses and E. coli. NC will develop an inactivated reovirus vaccine to test maternal protection of progeny against reovirus challenge in poults. NYC will analyze CIAV pathogenesis to understand how this viral DNA is maintained in flocks. The rCAN-based reporter systems will be used to examine putative response elements in the viral genome!&s promoter enhancer region for virus activation in the embryo. Experiments will infect chickens at different time points with CIAV and REV or MDV to examine the importance of CIAV infection prior to and after the generation of antigen-specific CTL for REV and MDV. Long-term plans will include the use of recombinant vaccines for CIAV to determine if vaccination will prevent the deregulation of CTL development. Project stations will evaluate CIAV status of various genetic stocks. Polycyclic halogenated hydrocarbons (TCDD, PCBs and PBBs) and polycyclic aromatic hydrocarbons (benzo[a]pyrene, DMBA) are immunotoxicants whose biological risk correlates with their ability to activate the aryl hydrocarbon receptor (AhR). TX will study the developmental toxicity induced by AhR ligands in the chicken embryo by comparative functional genomics. This work will identify altered genes expression after toxicant-induced AhR activation using available chicken immune cDNA microarrays from the Fred Hutchinson Cancer Research Center. NYC will target developmental timing of specific post-hatch immune functions using chemical/toxicological probes. Studies will probe timing of in ovo exposure and specific chemical actions that are likely to alter only a subset of the juvenile chicken!&s immune functions. Additional work will design strategies for protecting the developing chicken immune system against immune insult. NYC will develop methods to increase the efficiency of cell-mediated immune maturation during the last few days before hatching to enhance performance. TX will study the neuroendocrine (NE) circuits within the avian primary immune organs. Experiments will identify and characterize neuroendocrine messenger molecules secreted by the avian bursa of Fabricius and the thymus to determine their significance for the microenvironment to generate lymphocyte receptor diversity. The impact of locally produced NE substances on the ontogeny of the humoral and cellular immune system in birds will be determined. SC will examine the growth promoting factors of chicken Harderian gland cells. Proteins from supernatant fractions of homogenized Harderian glands will be isolated with monoclonal antibody affinity columns. Bioassays will be done using isolated proteins. DNA probes will be used to identify cytokines in the Harderian gland. AR will evaluate autoimmune Smyth line chicken, for the interrelationships between the melanocyte defect, the environment, and the immune system leading to autoimmune destruction of pigment cells. Special emphasis will be placed on the inherent pigment cell defect that leads to the pigment cell!&s recognition and targeting by the immune system. New research will examine the relationship between autoimmune thyroiditis and vitiligo in this line. AR will also study inflammatory mediators in the development of broiler ascites and on organ/tissue responses to antigens. Scleroderma (Sc) is an autoimmune, connective tissue disorder with excessive collagen deposition. The X-10 subgroup of Modified Wisconsin Line 3 Ancona show clinical signs similar to best Sc animal model, Line UCD 200. CA will compare the X-10, UCD 200, and normal tissues through microscopic studies. Serum samples from X-10, NIU, UCD 200 and normal birds will be tested for antinuclear antibodies by indirect immunofluorescence. Restriction fragment length polymorphism (RFLP) analysis will be used to determine if there is a defect in the collagen genes. PA will evaluate different photoperiod regimens and melatonin for effects on production performance and immune responses of broiler chickens. Investigations utilizing photoperiod and melatonin to alleviate the negative impacts of environmental stressors on broiler chickens will be initiated. PA will study different management practices, such as population density and environmental conditions, for effects on production performance as well as endocrine immune interactions in broilers and in laying hens. WAGENINGEN will focus on the effects of battery versus free range housing as well as steady state versus changing conditions on immune responses and gene expression in the lines selected for response to SRBC. Data suggest additive effects of housing (climatic) conditions and genotype on both immune responses and production parameters. The relationship between innate and specific immunity and the intestinal microflora (homotopic challenges) will be examined during immune system maturation in poults. Causal relationships between microflora, levels of innate antibodies and levels of specific antibodies will be studied. Work will explore the importance of naturally occurring antibodies particularly those reactive with the !'anti-Gal!( epitope (FRAMINGHAM). This surface molecule is widely distributed being found of on bacterial, viral and other microbial surfaces. Antibodies in high titer can be found in chickens, turkeys, and ducks. The functional significance of this antibody needs to be elucidated. It may serve as a good indicator of overall immunocompetence. OBJECTIVE 3. IA will investigate the relationships between the genes controlling growth and development, and those controlling vaccine response. A large F2 resource population from which many growth and body composition measurements have been collected, along with vaccine antibody levels to S. enteritidis (SE) will be studied. Parental lines for the cross included outbred broilers, inbred Leghorns and inbred Fayoumis. Primer sets will be developed that can be readily shared for use across many populations. Genes associated with growth and composition will be analyzed for relationship with SE vaccine responsiveness. After promising genes have been identified, advanced intercross generations (F8 to F13) will be evaluated for immunity, disease resistance and growth, to verify the relationships of genes with pleiotropic effects on both growth and immunity traits. ARS-PBESL will validate previous results on quantitative trait loci (QTL) associated with disease resistance. The station will identify candidate genes affecting disease resistance using a cDNA microarray. Five thousands unique genes, identified in the chicken intestinal EST library, will be used to analyze gene expression following Eimeria infection and vaccination. WAGENINGEN will develop microarray techniques to assess expression variation of known and positional candidate genes. Under dietary and immune modulation, chicken selection lines that differ both in immune responsiveness and production traits were less variable than the control line, suggesting genetic linkage or interaction influencing immune and production traits. A high-throughput DNA based typing test to replace serological typing of MHC haplotypes in broiler lines will be developed. Allele sequence information obtained for two class I loci B-FI and B-FIV will be used to design oligonucleotide probes specific for polymorphisms in the B-FIV locus (AL). NYC will determine which epitopes are recognized by MDV-specific CTL using two approaches. A cell line having TAP disrupted by a transfected selectable gene will be examined to determine if the TAP is no longer functional. A second approach uses insect cell lines expressing B21 and B19 MHC class I antigens, that lack TAP genes and cannot present epitopes. NYC will develop tetramer technology to enumerate MDV specific CTL to enable quantitative assessment of the genetic bases for CTL responses that are linked to genetic resistance. ARS-ADOL will develop a SNP test to identify a functional subgroup E receptor and endogenous virus ALV-E susceptibility. The test will then be applied to commercial lines to determine if subgroup E susceptibility has an effect on ALV-J susceptibility. NH will isolate L alloantigen system proteins from chickens having both L alleles on a common genetic background. The L proteins will be resolved by two-dimensional gel electrophoresis for proteomic analysis. NYC will refine juvenile-based immune assays that can accurately predict the immune and host resistance capabilities of the growing chicken. Cost-effective methods to assess immune capabilities will have utility for evaluating exogenous immunomodulation and for immune performance based breeder selection. ELISA development for a panel of chicken cytokines will proceed at ARS-PBESL. Chicken cytokine genes will be expressed in different vectors to produced recombinant proteins. Mouse monoclonal antibodies against cytokines will be produced. Indirect ELISAs will be developed using serum from coccidia-infected chickens. Stations will examine baseline cytokine values for different genetic stocks. ARS-ADOL will analyze various chicken lines, including the B congenics lines, for W interferon production in response to ALV and MDV infection. A capture ELISA will be used to analyze interferon produced after infection. The amount of interferon will be determined in cells cultured from infected animals. Serum enzymes are commonly used to evaluate the health status of animals, either individuals or groups. Normal values will vary depending on the genetic strain and the geographic location. CA will compared serum chemistries in age matched MD challenged and uninfected control birds. CA will collaborate with other stations to evaluate clinical chemistry baseline values and changes associated with additional diseases. Many studies are appropriately conducted at individual stations because of specific facilities, expertise and genetic resources. Other studies may involve shared expertise, resources including stocks and reagents for which this project has been a model.\

Measurement of Progress and Results

Outputs

• Maintain unique genetic lines and develop additional genetic material as needs arise.
• Identify candidate genes associated with immune response or disease resistance via microsatellite DNA markers, microarray technology or proteomic approaches.
• Develop transfected cell lines, antisera, cloned genes, primer sets, ELISA tests, and identification of differentially expressed proteins.
• Disseminate information through referred publications, symposia, invited lectures and informal discussions at national and international meetings.

Outcomes or Projected Impacts

• A safe, healthy food supply for consumers.
• Research will produce greater understanding of disease resistance and immunity.
• Production efficiency will increase due to greater disease resistance and improved immune responses.
• Newly identified genes will impact poultry health and animal agriculture in general.

Milestones

(2004): Identify candidate genes associated with antibody production or disease resistance via microsatellite DNA markers, microarray technology or proteomic approaches. Produce transfected cell lines, monoclonal antibodies and anitgneic peptides for further studies.

(2005): Develop ELISA tests and identify differentially expressed proteins to reveal genes that affect immunity or disease resistance. Use this information to continue project studies .

(2005): Investigate nutritional modulation of immunity to identify specific dietary ingredients that modulate immune function. Then use specific ingredients alone or in combination to test improved responses against disease.

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Projected Participation

View Appendix E: Participation

Outreach Plan

Industry stakeholders frequently attend the annual project meetings. This provides an opportunity for information exchange. For example, representatives of breeder organizations can learn of the latest genetic advances in disease resistance from the project scientists. Members of the technical committee can gain knowledge of emerging field problems that the project can address through experiments. The combined efforts of the NE-60 stations will generate new scientific data. Referred publications, symposia, invited lectures and informal discussions are some methods used to disseminate information. Project investigators have made significant scientific contributions to the improvement of poultry immune responses as well as the genetics of disease resistance. Cooperation among project members and with other researchers will remain a hallmark of NE-60. This cooperative effort will include sharing scientific expertise and genetic resources held at numerous project stations. The additon of several international members will expand the reach and influence of the effort.

Organization/Governance

The planning and supervision of the NE-60 Multistate Research project shall be the responsibility of the Multistate Technical Committee. The membership of this committee shall consist of an Administrative Advisor, a technical representative of each participating agency or experiment station, and a representative of the USDA Cooperative State Research Education and Extension Service (CSREES). The voting membership shall consist of the Technical Committee Representatives.
The Technical Committee shall be responsible for review and acceptance of contributing projects, preparation of reviews, modification of the multistate project proposal, and preparation of an annual report for transmittal by the Administrative Advisor upon approval to CSREES. Annual written reports will be prepared by each technical committee member and distributed at the annual meeting. A limited number of the compiled annual reports will be available upon request from the Administrative Advisor.

The Technical Committee will meet yearly and elect a secretary, who will serve the year after election and as the chairperson the following year. An Executive Committee will be formed to conduct all business of the Technical Committee between annual meetings. The Executive Committee shall consist of the current Technical Committee Chairperson, the Secretary, and the two immediate Past Chairpersons.
The chairperson may name other subcommittees as needed to perform specific assignments. They may include subcommittees to develop procedures, manuals, and phases of the multistate project, to review work assignments; to develop research methods, to prepare publications, and to write proposals.

Other agencies and institutions may participate and vote at the invitation of the Administrative Advisor. Minimum expectations for Technical Committee members are submission of a written annual report every year, and attendance at an annual meeting including presentation of research results at least one year out of two. Collaborators may include emeritus members with an interest in attending annual meetings, scientists who wish to contribute by virtue of having special expertise or interest, and those who engage in research interactions with an individual Technical Committee member. Collaborators should submit a written annual report every year, and present their progress when attending the annual meeting. Guests who attend an annual meeting through special connection to the Technical Committee (i.e. host institution) should make a brief presentation of their interests and ongoing research.

Literature Cited

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Al-Batshan, H. A., S. I. Al-Mufarrej, A. A. Al-Homaidan, and M. A. Qureshi, 2001. Enhancement of chicken macrophage phagocytic function and nitrite production by dietary Spirulina platensis. Immunopharm. Immunotox. 23:281-289.

Bacon, L. D., and R. L. Witter, 1994. B haplotype influence on the relative efficacy of Mareks disease vaccines in commercial chickens. Poult. Sci. 73: 481-487.

Bacon, L. D., H. D. Hunt, and H. H. Cheng, 2000. A review of the development of chicken lines to resolve genes determining resistance to diseases. Poult. Sci. 79:1082-1093.

Bacon, L. D., R. Vallejo, H. Cheng, and R. Witter, 1997. Failure of Rfp-Y genes to influence resistance to Mareks disease. Pages 69-74 In: Current Research on Marek's Disease. R. F. Silva, H. H. Cheng, P. M. Coussins, L. F. Lee, and L. F. Velicer, eds. Amer. Assoc. Avian Pathol., Kennett Square, PA.

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