Improving muscle growth and feed efficiency: Nottingham - Zoetis FLIP programme

Lead Research Organisation: University of Nottingham
Department Name: Sch of Biosciences

Abstract

This FLIP project is to support the exchange of staff between the University of Nottingham (UofN) and Zoetis (previously Pfizer Animal Health), the largest global animal health company based in Kalamazoo, MI, USA. There are specific areas of expertise that one partner has and the other partner would benefit from and it is this interchange of knowledge and expertise via a staff exchange programme that this proposal will fund. All these areas of interest relate to the primary aim of the research, to identify novel mechanisms of improving animal production efficiency.

The objectives of the project fall into 4 areas:
1. Bioinformatics and systems biology. The UofN have developed methodologies and systems for handling and analysing large datasets, which Zoetis would like to utilise. This will initially involve a bioinformatics specialist from Zoetis spending 6 months at the Advanced Data Analysis Centre (ADAC) at UofN, followed by the Director of Bioinformatics for ADAC visiting Zoetis for 1 month.

2. Determination of energy metabolism in cells and animals. Zoetis have experience in and the equipment for determining energy metabolism in cells (Seahorse analyser); whereas UofN have experience in and the equipment for determining energy metabolism in animals (mice and rats - CLAMS). Initially, a PDRA (to be appointed) from UofN will visit Zoetis for 1 month to validate the Seahorse (Extracellular Flux) analyser (to assess effects of novel target genes on muscle growth and metabolism, particularly nutrient utilisation efficiency) and then for 2 months to use it as a bioassay tool. Then University of Nottingham academics will visit Zoetis for 2 weeks to combine their expertise with that of Zoetis staff to identify effective and viable targets (from a separately funded project) which influence muscle growth and metabolism (nutrient utilisation). This will be a key step before then going on to manipulate these genes in an in vivo system (mice) in order to obtain proof of concept that the genes do alter muscle growth and feed efficiency, which is work to be funded as part of a BBSRC LINK grant currently under review or (if this is not successful) directly by Zoetis. Lastly, an in vivo specialist from Zoetis will visit UofN for 1 month to allow knowledge transfer of the in vivo methodologies already established there for measuring energy expenditure (CLAMS)in mice and rats.

3. Chick embryo manipulations. Zoetis are keen to develop their work in this area in order to identify agents (e.g. compounds) that influence growth and development of muscle and bone cells in chick embryos and thereby potentiate post hatch growth and welfare. This will initially involve a UofN academic visiting Zoetis for 1 week to explain the methodologies and establish exactly what Zoetis are wanting to do, before a poultry specialist from Zoetis spends 3 months at UofN learning the techniques.

4. Culture and working practices. The last objective is built into the other 3 objectives as it relates to all exchangers gaining experience of the culture, capabilities and working practices of the other partner (academic institution or large pharmaceutical company).

Planned Impact

The more immediate impact will be on the exchangers themselves. The exchange visits are targeted at specific areas of work and will therefore develop specific skills in those individuals and thereby enhance their capabilities at their home organisation. However the experience gained from simply visiting the other partner will broaden the exchangers' perspective as regards how research is done in a different environment, which may then impact upon the culture and working practices of the home organisation.

The overall aim of the work is to identify novel genes that may be drug targets to increase muscle growth and feed efficiency in pigs (and possibly other livestock), which will obviously benefit the Industrial partner, Zoetis, in their search for new drugs. However, Zoetis will not be the only beneficiary. From an academic point of view, the work will enhance our understanding of how muscle growth and metabolism are regulated at the molecular level. Importantly, this information may then be developed into a better understanding of other species, including man. Indeed, much of the early basic research on the use of growth promoters in farm animals has subsequently been translated into humans for the treatment of muscle-related diseases such as muscular dystrophies and sarcopenia. We therefore believe the work proposed will also eventually be translatable into human medicine.

The ultimate impact will be in the form of a drug that improves the efficiency of meat production, thereby contributing to the protection of food security worldwide. By making animal production systems more efficient, there will obviously be impacts on the farmers/producers, but also on the general public via improvements in food security (availability and/or cost of food).

Publications

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Description The purpose of this FLIP application was to support the exchange of staff between the University of Nottingham (UofN) and Zoetis, the largest global animal health company (previously Pfizer Animal Health), based in Kalamazoo, MI, USA. The overall aim was to enhance the ongoing research to identify mechanisms by which animal growth and feed efficiency (in pigs and chickens) can be improved, to enable the goal of sustainable intensification of livestock production to be achieved.
Several key staff from the UofN have visited the Zoetis main research site at Kalamazoo, USA. These visits have involved knowledge exchanges between staff on the two sites. This has enabled Zoetis staff to have deeper understanding of the biological mechanisms involved in animal growth and for UofN staff to have a better understanding of the commercial practice of identifying a biological target that can be manipulated using a pharmacological approach. The latter has shaped our current approach to research.
Through these interchanges UofN have helped to advise and thereby direct the focus of some of the research being carried out at Zoetis, both on pig and chicken production. As a result of the FLIP grant exchanges a member of staff from the UofN (Dr Dylan Sweetman) was recruited by Zoetis (Kalamazoo, Michigan, USA). He now current works as Principal Research Scientist in Zoetis's R&D research team identifying the mechanisms by which chicken growth efficiency could potentially be manipulated. In addition, the experiences of working with Zoetis, compared to their experiences in academia, has motivated the UofN Researcher to a gain employment as a Principal Research Scientist with a pharmaceutical-related company.
Through contributions of Zoetis staff whilst on placement at UofN, significant contributions have been made to bioinformatics and systems biology analysis of data sets. These contributions have been additive to data sets which have then resulted in published outputs (refereed conference abstracts and published paper), where we have described novel metabolic processes being associated with pig muscle growth. Currently additional manuscripts are being prepared which have been produced following inputs from Zoetis, particularly for the area of bioinformatics. Placements of staff from Zoetis have allowed knowledge transfer of techniques which assess the impact of novel genes on muscle growth using a mouse model system, as well as the use of equipment for assessing energy expenditure. These techniques are currently being evaluated at Zoetis (USA) for application to drug screening programs.
Exploitation Route Some of the interpretations of the data sets examining pig muscle growth carried out by visiting stafff from Kalamazoo have made a contribution to understanding the underlying mechanisms responsible. This information on fundamental aspects of muscle growth is directly translatable to human health, particularly conditions where muscle mass needs to be maintained, for example sarcopenia
Sectors Agriculture, Food and Drink,Healthcare

 
Description The purpose of this FLIP application was to support the exchange of staff between the University of Nottingham (UofN) and Zoetis, the largest global animal health company (previously Pfizer Animal Health), based in Kalamazoo, MI, USA. The overall aim was to enhance the ongoing research to identify mechanisms by which animal growth and feed efficiency (in pigs and chickens) can be improved, to enable the goal of sustainable intensification of livestock production to be achieved. The FLIP project has influenced career choices of two staff involved in this project. Through direct interaction with industry they were able to reflect on their career aspirations as well as their working conditions. Their choice has been to leave academic sector and work for companies involved in the pharmaceutical industry, one of them being the FLIP partner Zoetis. This has resulted in a loss of staff from the academic sector which will have an economic impact on the research outputs within this sector.
Sector Agriculture, Food and Drink,Pharmaceuticals and Medical Biotechnology
Impact Types Cultural,Societal,Economic

 
Description Direct award from Zoetis (industry award)
Amount £36,000 (GBP)
Organisation Zoetis 
Sector Private
Country United States
Start 04/2016 
End 11/2018
 
Title RNA-Seeker 
Description A web-app has been created allowing users to access RNA-seq data sets by species, tissue and experiment and then interrogate expression levels for groups of genes, by name/ID or gene ontology term. This allows expression data for orthologous genes of interest, from different tissues/experiments/species to be explored and compared. Although in some respect crude this simple comparison is potentially a way to quickly build and refute hypotheses concerning fundamental patterns in gene expression within and between species. The construction of "RNA-Seeker" web-app has, in part, been facilitated by utilizing the RNA-seq data sets from pig skeletal muscle, liver and adipose tissue generated from the research carried out in the project BB/J005320/1. This facility allows the exploration of orthologous genes in pigs across these three metabolically important tissues a resource which will be of value to the pig research community. Please note the http://Final address is pending server/firewall configuration 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact This data base is awaiting final validation but will be available in externally to the University of Nottingham in 2016. Although genomic database are available for pig this RNAseq generated database allows researchers to validate transcript expression in the three metabolic important tissues skeletal muscle, liver and adipose tissue in pig from "real" transcript expression profiles rather than those generated in silico. 
URL http://adac-genomics1.nottingham.ac.uk/RNA-Seeker/
 
Description BSAS invited talk 2017 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk entitled "Use of transcriptomics to identify mechanisms of improved growth and feed efficiency" presented at British Society for Animal Science conference in Chester, April 2017
Year(s) Of Engagement Activity 2017
 
Description Invited Speaker International Meat Science and Technology conference, Bangkok, Thailand 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk entitled "Stimulated muscle growth: the potential implications for meat quality"
Year(s) Of Engagement Activity 2016
URL http://icomst2016.com/
 
Description Invited Speaker at Nutrition Society Winter Conference (Dec 2014) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact oral presentation of abstract and discussion with professional from UK Nutrition community

Increased awareness of the mechanisms involved in muscle growth in livestock and potential translation of these observations to areas associated with human health.
Year(s) Of Engagement Activity 2014
 
Description Invited speaker Nutrition Society Student Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Invited talk entitled "Sustainability in animal nutrition"
Year(s) Of Engagement Activity 2016
 
Description Invited speaker at Nutrition Society Summer Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Selected as the Theme Leader's prize in Cellular and Molecular Nutrition, Nutrition Society Summer Conference for abstract - Skeletal muscle hypertrophy in pigs is associated with an increased expression of serine biosynthetic pathway genes along with genes associated with an endoplasmic reticulum stress. Oral presentation of abstract and discussions with professional from UK Nutrition community.

Increased awareness of the mechanisms involved in muscle growth in livestock and potential translation of these observations to areas associated with human health.
Year(s) Of Engagement Activity 2015
 
Description Invited speaker at Nutrition Society Summer Conference 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited talk entitled "Improving efficiency in meat production"
Year(s) Of Engagement Activity 2015
 
Description Invited speaker the Joint Annual Meeting of the American Society of Animal Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Seminar given by Dr John Brameld (CoI BB/J005320/1 and PI BB/MM001385/1) followed by questions and discussion with representatives of the animal production industry

Increased awareness within the animal production industry of the molecular mechanisms involved in promoting lean tissue growth.
Year(s) Of Engagement Activity 2015
URL http://m.jtmtg.org/abs/t/63802