Dr. Richard A. McIndoe, associate director of the MCG Center for Biotechnology and Genomic Medicine, has received a $15 million, five-year grant—MCG’s largest ever—to continue operating the Coordinating and Bioinformatics Unit for the innovative National Institutes of Health project, Animal Models of Diabetic Complications Consortium.
He also will begin providing the same services for the Mouse Metabolic Phenotyping Centers, another NIH-funded consortium of centers offering mouse-testing expertise to scientists nationwide for diseases including diabetes, obesity and related disorders.
The Animal Models of Diabetic Complications Consortium consists of 13 investigators generating ideas for mouse models, a Mouse Generation and Husbandry Core to generate the mice and the Coordinating and Bioinformatics Unit to oversee consortium activities.
“The NIH recognized years ago that there were few good animal models that mimic the complications of diabetes,” Dr. McIndoe said. Even the NOD mouse, a spontaneous model for type 1 diabetes, is inadequate, primarily because complications tend to come with age and mice have a relatively short lifespan.
Diabetes complications include cardiovascular and kidney disease, diabetic retinopathy and nerve and bladder damage. “Diabetic cardiovascular disease is probably the biggest mortality risk for types 1 and 2 diabetes; somewhere around 60 to 70 percent of diabetic mortality can be associated with cardiovascular disease,” Dr. McIndoe said.
The high risk of model development impeded financial support until the NIH committed funds several years ago. Scientists who receive funding agree to make their development data and resulting animal models available to the scientific community.
In 2001, while on the University of Florida faculty, Dr. McIndoe received the first grant to provide administrative and coordinating activities for investigators working on model development. Work includes organizing semi-annual Executive Steering Committee meetings, monthly teleconferences, workshops, training sessions and organizing activities for the External Advisory Boards.
A major task was developing a computer system that could store and analyze the huge amount of data generated by investigators, then share it with scientists worldwide through a Web portal, www.amdcc.org.
“We have to have a way of storing and capturing all that information in an efficient way so another researcher can go back and do the same experiment or analyze it in real time,” Dr. McIndoe said. “You also need to store information flexibly so they can grab the information any way they want. We are constantly adding statistical analysis so data can be analyzed quicker.”
To date, about 70 animal models have been studied, information on about 25 has been deposited in the database Dr. McIndoe developed and about 20 of those models will soon be available from mouse repositories. Scientists will generally need several models to mimic human disease. “They don’t want an animal model that looks like a mouse problem; they want an animal model that looks like a human problem,” Dr. McIndoe said.
For the second round of NIH funding, each investigator will propose two new models and turn them over to a husbandry core for development. “Once created, the models will be sent back to the investigators, who will be in charge of understanding the pathology of the complications,” said Dr. McIndoe.
The NIH integrated operation of the consortium with the Mouse Metabolic Phenotyping Centers, which also were up for grant renewal. The centers’ first round of funding didn’t include money for administration and bioinformatics, but it was quickly determined both were needed.
“The centers bring to the general scientific community a low-cost way of doing a variety of metabolic assays on mice that would be cost-prohibitive to set up in your local lab,” Dr. McIndoe said. For a small fee, centers will characterize mouse metabolism, blood components including hormones, energy balance, eating and exercise, organ function and form, physiology and histology. For more information about services and fees, visit www.mmpc.org.
The University of Cincinnati, Vanderbilt University and the University of Washington have been designated as Mouse Metabolic Phenotyping Centers. MCG’s Coordinating and Bioinformatics Unit is soliciting additional centers, which will be funded through a subcontract with MCG.
The Animal Models of Diabetic Complications Consortium and the Mouse Metabolic Phenotyping Centers will continue to function autonomously. But Dr. McIndoe has gutted the infrastructure he created for the consortium to accommodate the workings of both. “The face of it will be individual, but the underlying software architecturally works together.”
“This grant, the largest award ever received by MCG, is on target with the NIH’s initiatives to accelerate translation of scientific discoveries into improved health care,” said MCG Vice President for Research Frank Treiber.
“The grant will greatly strengthen our external competitiveness for other center grants,” said MCG School of Medicine Dean D. Douglas Miller. “It also will help our internal planning efforts in the area of data coordination for clinical translational research, a major strategic focus of the school.”
At MCG, Dr. McIndoe also is the local director of informatics for two major newborn screening studies for type 1 diabetes and co-principal investigator on studies seeking type 1 diabetes biomarkers.
- Toni Baker