Morris Goodman, Ph.D.; Lawrence Grossman, Ph.D.; Leonard Lipovich, Ph.D.; Derek Wildman, Ph.D.; and Harry Chugani, M.D.; will serve as co-investigators in the research for the School of Medicine. The NSF awarded the team $1.7 million for its project.
The School of Medicine team is working on the research with Monica Uddin, Ph.D., of the University of Michigan’s School of Public Health, and Christopher Kuzawa, Ph.D., of the Northwestern University School of Medicine.
The NSF awarded an $800,000 companion grant to co-investigators Chet Sherwood, Ph.D., of George Washington University, and Patrick Hof, M.D., of the Mount Sinai School of Medicine.
“Collaborative Research: Evolutionary Origins of the Brain Energetics and Adaptive Plasticity of Humans” will seek to discover why the human brain learns at such a high rate during childhood and adolescence, but then sees that ability plateau or decrease in later years. The researchers will study a corresponding curve in primate brains’ consumption of glucose, which is intriguingly different from the human curve, and attempt to explain the difference.
“The brain’s capacity for learning (plasticity) is greatest during childhood, and involves the formation and refinement of new neuronal connections,” Dr. Goodman explained. That process is driven by high rates of glucose consumption in the brain.
The team will study key aspects of evolutionary genomics, including comparing RNA diversity and structure between the human brain and the gorilla brain, and attempt to determine which brain genes involved in human-specific aspects of metabolism have human-specific evolutionary changes at their "on/off switches," known as gene promoters, Dr. Lipovich said.
“If we can find the gene that tells us to turn off the glucose consumption in the brain, perhaps we can determine how to tell it to stay on, or turn back on,” Dr. Lipovich said. That could lead to increasing the “shelf-life” of brain plasticity, which could result in increased learning capacity beyond the current peak years of childhood and adolescence.
The School of Medicine’s interdisciplinary research team will use positron emission tomography scans of brain glucose consumption. Members will integrate the results with patterns presented by RNA and protein data on the thousands of genes expressed at changing levels in brain regions across similar developmental stages.
To determine whether molecular and cellular change in human brain development is distinctive to humans, the researchers will incorporate comparative data from great apes and macaque monkeys, our close relatives.
Dr. Goodman said the team expects to find “coordinated expression patterns” in energetic and brain plasticity genes, evidence that adaptive evolution occurred “in their regulatory machinery during the origin of humans.” The results, he hopes, will provide clues about brain plasticity that gives humans their capacity to incorporate experience and learning into the production of culture.
The research, while focusing on adaptive brain plasticity, may serve as a potential springboard for further research into diseases of the brain that involve altered plasticity, such as epilepsy and Alzheimer’s, Dr. Lipovich said.
“There is still much to discover about this so-called ‘junk DNA’ that we haven’t yet identified as having a purpose,” Dr. Lipovich said. A key, and completely unique, aspect of this research will be to monitor RNA in the brain that does not encode proteins. The "junk DNA" may encode tens of thousands of kinds of new RNA molecules that regulate proteins in the brain, although they themselves do not encode proteins. The group is poised to secure a pioneering glimpse of non-protein-coding RNA in human evolution and the brain.
The findings should attract interest across a number of fields, including anthropology, neuroscience, molecular evolution, bioenergetics, endocrinology and pediatrics.
Dr. Goodman is a Wayne State University School of Medicine distinguished professor of anatomy. Dr. Grossman, professor of Molecular Medicine and Genetics, is the Henry L. Brasza director of the Center for Molecular Medicine and Genetics. Dr. Wildman is assistant professor in WSU’s Center for Molecular Medicine and Genetics, and Department of Obstetrics and Gynecology, and a member of the Perinatology Research Branch. Dr. Chugani is a professor of Pediatrics, Neurology and Radiology. Dr. Lipovich is an assistant professor for the Center for Molecular Medicine and Genetics, and Neurology.