Two national diabetes-related initiatives coordinated by MCG bioinformatics expert
A national effort to develop animal models to study the devastating complications of diabetes is being coordinated by a Medical College of Georgia bioinformatics expert.
Dr. Richard A. McIndoe, associate director of the MCG Center for Biotechnology and Genomic Medicine, has received a $15 million, five-year grant – the largest ever received by MCG – 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 expertise in sophisticated, expensive mouse testing to scientists nationwide for a variety of diseases including diabetes and its complications as well as obesity and related disorders.
The Animal Models of Diabetic Complications Consortium consists of 13 investigators from different institutions generating ideas for creating 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 says. 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, he says.
Complications include cardiovascular and kidney disease, diabetic retinopathy as well as damage to the nerves and bladder. "Diabetic cardiovascular disease is probably the biggest mortality risk for type 1 and 2 diabetes; somewhere around 60 to 70 percent of diabetic mortality can be associated with cardiovascular disease," Dr. McIndoe says.
Unfortunately, the high risk of model development impeded financial support until several years ago when NIH opted to commit funds to make it happen, he says. 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 and training sessions and organizing activities for the External Advisory Boards.
A major task was developing a computer system that could take the huge amount of data generated by investigators, store it, analyze it in a flexible way and enable scientists all over the world to access it 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 says. "You also need to store information in a way that is very flexible 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 for ordering from mouse repositories. Interestingly, there is not necessarily a definitive model for even a single complication, rather an array of models will be necessary as researchers manipulate genes to try and 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," he says.
As NIH looked at a second round of funding for the consortium, it took a fresh approach with each investigator proposing two new models and turning 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," says Dr. McIndoe, noting the operational changes reflect the complexity and magnitude of the work.
NIH also opted to integrate 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," he says. "For example, if you don't have a small-animal MRI unit on your campus, there is no way you can do some of these assays." 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. Additional centers are being solicited through the Coordinating and Bioinformatics Unit at MCG and will be funded through a subcontract with MCG, Dr. McIndoe says.
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 AMDCC 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," says Dr. Frank Treiber, MCG vice president for research. "Dr. McIndoe's work will speed the process of understanding the complex interplay between genetic and environmental factors in the development of human diseases such as diabetes and cardiovascular diseases by enabling investigators across the nation to collaborate more efficiently. The scientific community and ultimately all of us benefit from these collaborations that enable access to such rich data bases and promote quicker scientific breakthroughs resulting in improved public health."
"The MCG School of Medicine is pleased with this major NIH award to Rick McIndoe, which will greatly strengthen our external competitiveness for other center grants," says Dr. D. Douglas Miller, dean of the School of Medicine. "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. The studies are following thousands of patients over many years, collecting detailed data on everything from their infections to what that they eat to their fingernail clippings. He also is co-principal investigator on studies looking for biomarkers for type 1 diabetes.
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