James MacLeod, John S. and Elizabeth A. Knight chair and professor of veterinary science at the Maxwell H. Gluck Equine Research Center and director of UK's Equine Initiative, was recently awarded two grants totaling more than $1.1 million over three years. Three other equine researchers in UK's College of Agriculture were also collectively awarded more than $500,000.

MacLeod's grant was awarded by the National Science Foundation in support of his and a team of collaborators' computational work on the mRNA transcriptome.

"As an equine scientist, it is very gratifying to obtain a large grant from the National Science Foundation for a project with direct relevance to equine health research," MacLeod said.

According to MacLeod, research that determined the primary DNA base sequence of the horse genome was completed in 2007 and 2008. And while it is a major accomplishment, in many ways it is just the beginning. Distributed within the 2.7 billion bases of DNA that compose the equine genome are approximately 20,000 protein-encoding genes. Understanding the structure of these 20,000 genes, what tissues express which genes, when the genes are expressed and how much they are expressed represent functional parameters studied by many scientists working on equine health and disease. 

The grant will be used to develop computer-based analytical methods to study gene expression. MacLeod and other collaborators are using data generated from a number of horse tissues through a process called RNA sequencing, a new technology for analyzing gene expression that enables an assessment of all genes concurrently, not just individual genes or small groups of genes. Funding from the grant will be used for software development, student support and experimental testing of the new computational algorithms.

MacLeod's collaborators for this grant are Jinze Liu, faculty member in the department of computer science at UK, Arne Bathke, faculty member in the department of statistics at UK; and Jans Prins, department chair of computer science at University of North Carolina - Chapel Hill.

"Determining the nucleotide sequence of the equine genome and several emergent DNA sequencing technologies are opening exciting new opportunities to study gene expression.  Changes in gene expression underlie many disease processes and treatment mechanisms.  The computational algorithms that we are working to develop will greatly facilitate the analysis of gene expression based on direct RNA sequencing approaches," MacLeod said.

The second grant, a fellowship grant totaling $100,000 to be paid over two years, was awarded by the Morris Animal Foundation. This grant will provide stipend support for graduate student Jennifer Janes and her project on equine cervical stenosis, commonly known as Wobbler Syndrome, a structural narrowing of the spinal canal in the neck that produces severe neurological deficits through spinal cord compression.

Wobbler Syndrome is a devastating disease targeting the musculoskeletal and neurological systems of horses. It is a distressing disease for owners of affected horses with limited treatment options. Multiple factors are thought to contribute to development of this disease including genetics, high planes of nutrition, trauma, rapid growth and altered copper/zinc levels. The cause and development are not well understood. The focus of this project will be the examination of the role of abnormal bone and cartilage formation in neck vertebrae, as well as the identification of regions of DNA and specific genes that are involved in the disease process.

"Malformations of vertebrae in the neck of horses that pinch the spinal cord are all too common. The resulting neurological deficits can be very serious, even to a point where the horse is a danger to itself and anyone around it. Sadly, euthanasia is a frequent outcome," MacLeod said. "New imaging and genomic technologies developed over the last several years will enable us to re-examine this disease with the aim of improving our understanding of its cause and progression."  

Collaborators are veterinarians Steve Reed and Katie Garrett at Rood & Riddle Equine Hospital in Lexington and Neil Williams, associate director of UK's Livestock Disease Diagnostic Center.

"I think it is a good example of collaboration between Gluck, LDDC and veterinary practitioners," MacLeod said. "Also, the training of the next generation of veterinary scientists is a critical issue for everyone concerned about advances in equine health going forward.

"The Morris Animal Foundation has been a leader in developing funding opportunities that encourage young veterinarians such as Dr. Janes to pursue career paths that include discovery research on animal health problems," MacLeod added. 

MacLeod's grants follow on the heels of two other large competitive research grants secured by scientists in the Gluck Center. Chuck Issel, Wright-Markey Chair in Equine Infectious Diseases at the Gluck Center, was awarded $347,500 per year for a multi-year project funded by the National Institutes of Health for a project called "Equine Infectious Anemia Virus Envelope Variation and Vaccine Efficacy." Ernie Bailey was awarded $28,125 from the Morris Animal Foundation for "Continuation of SNP Gene Mapping Projects."

In addition, Kristine Urschel, faculty member and researcher in UK's Department of Animal and Food Sciences was awarded a First Award Grant for Young Investigators from the Morris Animal Foundation. The two-year grant totaling $100,000 will examine maintaining muscle mass in older horses and will be overseen by David Horohov, William Robert Mills Chair in Equine Immunology at the Gluck Center.

"As horses age, they experience declines in muscle mass that affect their health and performance. We will investigate how age, inflammation and Cushing's disease affect the horse's protein metabolism. This research will provide valuable information about protein metabolism in older horses and allow for improved diet formulation and management strategies," Urschel explained.

"The accomplishments of these talented faculty attest to the confidence the College of Agriculture has placed in its array of programs that make up the Equine Initiative. These projects are relevant to Kentucky's signature industry, but they also confirm that our faculty are competitive in national and international arenas," said Nancy Cox, associate dean of research in UK's College of Agriculture and Agricultural Experiment Station director.

"I congratulate faculty at the Gluck Equine Research Center and across the College of Agriculture for their success in attracting significant research support from federal and industry-based research agents. Their success is a testimony of the quality and the importance of their work to the scientific community and equine industry. We are fortunate to have some of the best faculty, staff and graduate students in the world here," said Mats Troedsson, chair of UK's Department of Veterinary Science and director of the Gluck Center.