Funded PhD Studentship: Leveraging metabolomics to reduce copper toxicity in dairy cattle

Agriculture & Environment

Primary supervisor: Dr James McCaughern, Harper Adams University

Second supervisors: Dr Joe Roberts, Dr Sandy Mackenzie and Professor Liam Sinclair

Project Title: Leveraging metabolomics to reduce copper toxicity in dairy cattle

Successful candidates will receive a yearly stipend (paid monthly) set at the UKRI rate - for 2024/5 this will be £19,237. Harper Adams University is unfortunately unable to offer a fee waiver for international students applying and evidence of funding will be required for International Fee paying students to show they can cover the difference between the UK and international fees for the full four years - for the 2024/5 academic year this amount is £10,890.  However, scholarships maybe be available at the time of appointment to cover the difference between UK and International fees for the duration of the programme.  

During this studentship, the successful applicant is expected to develop sought-after technical skills in the fields of animal nutrition, health and welfare. Applicants must hold a minimum of a 2:1 or equivalent bachelor's degree in an appropriate subject /high grade point average bachelor's degree for international applicants or a 2.2 alongside a suitable Master's Degree. Potential for research based on alternative qualifications/experience as judged acceptable by the university, will be considered on a case by case basis.

Project description:

Background:

Metabolomics is a technique that utilises advanced analytical chemistry to provide researchers with a more complete picture of the animal’s phenotype at the metabolic level (Taylor et al., 2022). The ability to detect and quantify a large number of metabolites within a single sample is helping develop a greater understanding of systems-wide biology across a range of scientific disciplines, and to identify new diagnostic tests (Monteiro et al., 2013). Despite increasing popularity within other fields, the ability to generate significant steps forward within animal science remains relatively untapped.  

One such area where metabolomics can serve to improve animal health, welfare and performance is the dietary supplementation of copper (Cu) to dairy cattle (Atkins et al., 2021; Sinclair et al., 2013; 2017). There are many biological consequences of an inadequate dietary Cu supply, such as anaemia and impaired growth (Suttle et al., 2022). In contrast, there is now substantial evidence of a significant over-supply of Cu to winter-fed dairy cattle within the UK, with a mean dietary Cu concentration of 28 mg/kg of DM reported by Sinclair and Atkins (2015), well in excess of the recommended 9-11 mg/kg DM (NASEM, 2021; NRC, 2001). Reasons for this elevated Cu-status on farm are unclear, but may result from a perception within the feed industry that “more is better” (McCaughern et al., 2020). However, recent evidence from long-term studies at Harper Adams University has clearly demonstrated significant sub-clinical consequences as a result of over-feeding Cu (McCaughern, 2020). For example, McCaughern et al. (2024) identified both a decline in fertility, coupled with negative effects on liver function and the immune system when replacement Holstein-Friesian dairy heifers were fed dietary Cu concentrations above requirements. Milk yield and fertility in early lactation were also compromised (McCaughern, 2020). These findings provide very strong evidence for a revision of Cu feeding limits, both nationally and internationally. Metabolomics can add further weight to these arguments by identifying the key biological pathways responsible for these phenotypic changes, as well as identifying new indicators of Cu status.  

Aims and objectives:

To utilise samples that have been biobanked from previous research studies on the bioavailability of Cu and the long-term effect of over-feeding Cu to growing and lactating dairy cattle to:

1. Profile the biological changes which occur in dairy cattle as a result of an altered Cu status;
2. Identify novel indicators of Cu status and toxicity in growing and lactating dairy cattle 
3. Produce 3 to 4 internationally excellent papers in peer reviewed journals

Methodology: 

Six dairy cattle studies have been undertaken at Harper Adams University in the last 10 years to determine factors influencing Cu availability and the effect of long-term over-feeding of Cu on growing and lactating dairy cattle (Atkins et al., 2020; McCaughern et al., 2020, 2024; Sinclair et al., 2017, Williams et al., 2024). During these studies intake, fertility and milk yield were recorded, and the Cu status and immune function monitored through regular blood and liver biopsy sampling. These samples have been biobanked pending further analyses. In this project blood plasma samples will undergo non-targeted metabolomic analysis according to Icely et al. (2024- pre-submission), to determine the changes in the animal’s metabolism. Blood plasma collected concurrently with liver samples will also be used to scope novel indicators of Cu status, and help facilitate the development of new veterinary tests for Cu status and toxicity in cattle.        

Candidates are encouraged to contact Dr James McCaughern to discuss the project before applying if they wish to.

Contact:Dr James McCaughern, Harper Adams University