Location: Research Programs
Project Number: 3022-32000-018-032-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2023
End Date: Aug 31, 2025
Objective:
New approaches to understanding host immune responses to infection are needed to advance livestock health research, including studies of disease pathogenesis and correlates of disease resistance. Currently, the field is stymied by the lack of conventional immunological reagents such as antibodies and cytokine measurement tools. However, the use of next gen host transcriptome sequencing technologies provides a solution to the problem by elucidating cellular immune responses at unprecedented detail while bypassing the need for conventional immunological reagents. Such approaches have begun to revolutionize the study of human diseases in the last 5 years and can be readily applied to study livestock disease as well. We propose therefore to use RNA sequencing (including scRNAseq, bulk RNAseq, and deconvolution algorithms) to develop an atlas of the airway and blood immune cell populations of healthy cattle, and how these populations change in response to shipping stress and to pneumonia. We will also define the changes that occur in these cell populations as the immune system matures in the first year of life. We have already completed initial scRNAseq and bulk RNAseq on airway cells from healthy cattle and are therefore confident we have advanced cell preparation and bioinformatic tools required to complete the proposed studies in cooperation with the USDA ARS.
Approach:
The Cooperator proposes to conduct three studies to create a new atlas of airway cells and circulating leukocytes in cattle and how these cells respond to stress, infection, and age maturation. The data from these studies will form the foundation of a new approach to investigating immune responses and disease pathogenesis in cattle and the information can also be used to complement and extend conventional immunological investigations and provide new target leads.