New scientific discoveries - with collaborators
1. New standardised assays for measuring immunity (called immune phenotypes): Without measurement, progress is slow. We developed an ImmunoChek (or Ichek) assay to measure informative read-outs in whole blood from cattle in response to bacterial and viral antigens. Using IChek, we plan to conduct baseline studies of the immune response, from which disease-associated and pathological biomarkers can then be developed.
2. Assessment of vitamin D status in Spring-born dairy calves for the first time: Vitamin D has long been known to be important for bone growth, but more recently its extensive involvement in the immune response has also been recognised. However we had no prior information on the Vitamin D status of Irish livestock. Our analysis shows that calves are low in vitamin D and we are currently investigating the impact this has on disease susceptibility.
3. Discovery and characterization of new host defence peptides (HDPs) in multiple livestock species: Using a comparative genomics approach, we have identified novel HDPs in cattle, horses and sheep. These suites of natural antibiotics hold exciting potential as adjunct or alternatives to antibiotics. They have published efficacy against bacteria, viruses, parasites and fungi!
4. Identification of a role for bovine HDPs in bull fertility: Knocking these genes out in mice results in male sterility and men with mutations in these genes are less fertile. We have shown that these genes play a role in bull fertility too, for the first time.
5. First assessment of a role for methylation in the regulation of the T cell response in cattle with TB: TB continues to pose enormous challenges for livestock as well as humans. Understanding the role of the epigenome, and identifying epigenetic differences as a result of infection is another critical piece of the picture to improve diagnosis and treatment options.
6. Identification of differentially expressed antimicrobial peptides in the salivary gland of cattle with Johne's disease: Despite the vast majority of infectious diseases being spread via the faecal-oral route we know very little about protective mechanisms in the oral cavity in livestock. This study has identified the immune competency of the salivary gland in cattle and also some potential targets that may play a role in anti-mycobacterial defence.
7. Detection of inflammatory biomarkers in cervical mucus from cows with endometritis: The modern dairy cow is not unlike a high performance athlete and requires all available energy to support her physiology during calving. Fighting an infection, either at a clinical or sub-clinical level depletes her energy reserves which has a production and fertility cost. Our study evaluated the occurrence of uterine disease (Endometritis) in Irish dairy cows under a pasture based system. We also identified some key immune changes in the early post-partum period that sets some cows up on a disease trajectory! We can now measure these markers in cervical mucus - a non-invasive way to detect disease.
8. Identification of genes associated with resistance to Johne's disease: Breeding for improved disease resistance is a key goal of many livestock immunologists/geneticists. Disease resistance is a trait affected by multiple genes, the vast majority of which we have yet to identify. We have performed some analyses that not only help us understand the disease process (pathogenesis) but could also ultimately be used to improve disease resistance.
9. Identified new strategies to enhance vaccine efficacy: A number of factors contribute to variable responses to vaccination in neonatal calves, principally due to the immature nature of the developing immune system. We have identified targets, and vaccine adjuvants that activate these targets to drive enhanced cell-mediated immunity (CMI). CMI is particularly important for pathogens which internalise inside host cells such as viruses, and mycobacteria.
2. Assessment of vitamin D status in Spring-born dairy calves for the first time: Vitamin D has long been known to be important for bone growth, but more recently its extensive involvement in the immune response has also been recognised. However we had no prior information on the Vitamin D status of Irish livestock. Our analysis shows that calves are low in vitamin D and we are currently investigating the impact this has on disease susceptibility.
3. Discovery and characterization of new host defence peptides (HDPs) in multiple livestock species: Using a comparative genomics approach, we have identified novel HDPs in cattle, horses and sheep. These suites of natural antibiotics hold exciting potential as adjunct or alternatives to antibiotics. They have published efficacy against bacteria, viruses, parasites and fungi!
4. Identification of a role for bovine HDPs in bull fertility: Knocking these genes out in mice results in male sterility and men with mutations in these genes are less fertile. We have shown that these genes play a role in bull fertility too, for the first time.
5. First assessment of a role for methylation in the regulation of the T cell response in cattle with TB: TB continues to pose enormous challenges for livestock as well as humans. Understanding the role of the epigenome, and identifying epigenetic differences as a result of infection is another critical piece of the picture to improve diagnosis and treatment options.
6. Identification of differentially expressed antimicrobial peptides in the salivary gland of cattle with Johne's disease: Despite the vast majority of infectious diseases being spread via the faecal-oral route we know very little about protective mechanisms in the oral cavity in livestock. This study has identified the immune competency of the salivary gland in cattle and also some potential targets that may play a role in anti-mycobacterial defence.
7. Detection of inflammatory biomarkers in cervical mucus from cows with endometritis: The modern dairy cow is not unlike a high performance athlete and requires all available energy to support her physiology during calving. Fighting an infection, either at a clinical or sub-clinical level depletes her energy reserves which has a production and fertility cost. Our study evaluated the occurrence of uterine disease (Endometritis) in Irish dairy cows under a pasture based system. We also identified some key immune changes in the early post-partum period that sets some cows up on a disease trajectory! We can now measure these markers in cervical mucus - a non-invasive way to detect disease.
8. Identification of genes associated with resistance to Johne's disease: Breeding for improved disease resistance is a key goal of many livestock immunologists/geneticists. Disease resistance is a trait affected by multiple genes, the vast majority of which we have yet to identify. We have performed some analyses that not only help us understand the disease process (pathogenesis) but could also ultimately be used to improve disease resistance.
9. Identified new strategies to enhance vaccine efficacy: A number of factors contribute to variable responses to vaccination in neonatal calves, principally due to the immature nature of the developing immune system. We have identified targets, and vaccine adjuvants that activate these targets to drive enhanced cell-mediated immunity (CMI). CMI is particularly important for pathogens which internalise inside host cells such as viruses, and mycobacteria.
Immunological tools developed - with collaborators
- Novel assays to measure the immune response in cattle ex-vivo and in-vitro. These low cost assays could also be easily adapted for use in any other species.
- Optimised assays to measure biomarkers in cervical fluid of the post-partum cow. These tools have the potential to reduce the requirement for invasive sampling and therefore are welfare friendly.
3. Primary cell culture models: While whole-animal models are critically important to understand the whole picture of health and disease, cell lines can be used to assess specific questions and reduce the requirement for animal infection studies. Furthermore, primary cells are preferable as they are more physiologically relevant than immortalised cell lines.
- Salivary epithelial and fibroblast cell culture model
- Uterine endometrial epithelial and stromal cells
- Nasal epithelial cells
- Tracheal epithelial cells
- Mammary epithelial cells
- Primary fibroblast cells, including from the ear.
4. We have identified small molecule inhibitors that target the inflammasome to reduce inflammation in bovine cells in vitro. These are potential new drugs that now require assessment in vivo.
5. Novel effective adjuvants to drive cell-mediated immunity and enhance vaccination efficacy.
- Salivary epithelial and fibroblast cell culture model
- Uterine endometrial epithelial and stromal cells
- Nasal epithelial cells
- Tracheal epithelial cells
- Mammary epithelial cells
- Primary fibroblast cells, including from the ear.
4. We have identified small molecule inhibitors that target the inflammasome to reduce inflammation in bovine cells in vitro. These are potential new drugs that now require assessment in vivo.
5. Novel effective adjuvants to drive cell-mediated immunity and enhance vaccination efficacy.