Location: Animal Parasitic Diseases Laboratory
Project Number: 8042-31000-107-000-D
Project Type: In-House Appropriated
Start Date: May 15, 2017
End Date: Dec 15, 2021
Objective:
Objective 1. Determine the change in the intestinal metabolome and microbiome during parasitic nematode infection and after anti-parasitic clearance.
Sub-objective #1. Characterize parasite-induced molecular mechanisms that modulate intestinal inflammation.
Sub-objective #2. Evaluate the potential impact of Cry5B on the native and parasitized gut microbiome.
Objective 2. Identify pan-nematode secretome products with immune modulating activity that along with nutritional supplements eliminate parasites and enhance enteric health.
Sub-objective #1. Use antibodies from parasite infected pigs and goats to select for immunogenic cloned parasite products that have been computationally identified as vaccine targets.
Sub-objective #2: Test for cloned parasite products that induce innate immune responses at the mucosal surface of explanted intestinal tissues from pigs and goats.
Approach:
Objective 1. Determine the change in the intestinal metabolome and microbiome during parasitic nematode infection and after anti-parasitic clearance.
Sub-objective #1. Characterize parasite-induced molecular mechanisms that modulate intestinal inflammation.
Hypothesis #1: Parasitic infections alter the relative abundance of butyrate-producing bacteria in the gut and change the composition and concentration of total short-chain fatty acids (SCFA) as well as anti-inflammatory butyrate, which in turn modulates intestinal inflammation and host immunity.
Sub-objective #2. Evaluate the potential impact of Cry5B on the native and parasitized gut microbiome.
Hypothesis #2: The administration of the Cry5B anthelmintic will have minimal effects on the native microbial community in the gut due to its transient nature and invertebrate gut targets.
Hypothesis #3: Parasite-induced changes in the microbiome will be restored to the native structure and function after treatment with Cry5B that reduces worm burden.
Experimental design: Quantifying changes in the intestinal metabolome and gut microbiome induced by parasitic infection, and characterizing the abilities of anti-parasitic treatments to restore altered gut microbiota, are important in dissecting mechanisms of host pathophysiology and immunity. We will conduct an in-depth comparison of the gut metabolome and microbiome between animals randomly assigned to two conditions (naive and infected) and exposed to Cry5B in an optimally determined delivery system.
Objective 2. Identify pan-nematode secretome products with immune modulating activity that along with nutritional supplements eliminate parasites and enhance enteric health.
Sub-objective #1. Use antibodies from parasite infected pigs and goats to select for immunogenic cloned parasite products that have been computationally identified as vaccine targets.
Hypothesis #1: Immunization of target host species with computationally selected immunogenic cloned parasite products will disrupt parasitism and prevent infections.
Sub-objective #2: Test for cloned parasite products that induce innate immune responses at the mucosal surface of explanted intestinal tissues from pigs and goats.
Hypothesis #2: Selected cloned immunogens that also have innate immune features defined by responses in intestinal explants will enhance vaccine efficacy and disrupt parasitism.
Experimental design:
Powerful new technologies to characterize the transcriptomes from multiple life stages of parasitic nematodes (Heizer et al., 2013) can be used to predict secreted peptides common to the pan-secretome. Combining this bioinformatics approach with antibody detection systems of immune peptides and innate responses of intestinal explanted tissues from pigs and goats will be used to identify vaccine candidates for immunization in the target host species of interest.
