Wright State University announced today that is has received a prestigious Program Project Grant (PPG) from the National Institute of Neurological Disorders and Stroke (NINDS). The $4.8 million grant is the first Program Project Grant Wright State University has received. Five university scientists will use the grant to further their research into why full recovery is not always achieved after damaged nerves have regenerated.
"These grants are extremely competitive, and this award underscores the high caliber of neuroscience research being conducted at Wright State," said David R. Hopkins, president of Wright State. "In this research arena we are successfully competing at a national level. We are extremely proud that Wright State has taken a leadership role by bringing this Program Project Grant to the region."
Program Project Grants are designed to "encourage multidisciplinary research approaches to a diverse array of nervous system disorders," according to NINDS, one of the 27 institutes and centers that comprise the National Institutes of Health, and the guidelines require at least three interrelated projects that contribute to the program objective. Five collaborative projects, each led by a Wright State NIH-funded investigator, will work together to better understand the recovery-or lack of it-from neurotrauma.
The team of Wright State investigators-Drs. Francisco Alvarez, Timothy Cope, Kathrin Engisch, Robert Fyffe and Mark Rich-are accomplished researchers in fields covering developmental biology, synaptic function and sensorimotor behavior of the spinal cord and peripheral nervous system. The diversity of their analytical viewpoints will, through this grant, create a synergy of research information focused on a common interest. (see sidebar on the five projects)
When the Connections No Longer Work: After Nerves Regenerate
Our wired communication system sends and receives electrical impulses from the central nervous system (CNS) through a highly specialized peripheral nervous system (PNS), which transmits sensory information and controls movement. The PNS relays messages from the body to the brain and regulates internal processes. When the PNS is damaged, nerve activity may be blocked, interrupted or completely disrupted, depending on the severity of the injury.
Damage to the PNS, peripheral neuropathy, includes more than 100 classifications, each unique in its presenting symptoms, based upon the type of nerves damaged-motor, sensory, or autonomic, or a combination of these. The most common cause of peripheral neuropathy is trauma. But, chemotherapy and a wide range of systemic diseases, including diabetes mellitus, vascular disease, and kidney disorders, also damage nerves and neuronal cells. Unlike the CNS, the PNS can regenerate both neurons and nerve circuitry.
"We know that damaged peripheral nerves regenerate, but regeneration is not synonymous with recovery," said Timothy Cope, Ph.D., professor and chair of the Department of Neuroscience, Cell Biology, and Physiology in WSU's Boonshoft School of Medicine, director of the school's new Comprehensive Neuroscience Center, and principal investigator on the PPG. "Neither sensation nor movement return to pre-injury levels after nerve regeneration. Although regeneration of the PNS is necessary to restore voluntary movement, injury initiates changes in the spinal cord that do not reverse with regeneration. Problems remain in timing and strength of muscle contraction, problems that are essential to normal movement."
The goal of Wright State's Program Project Grant is "to understand how injury, regeneration and alterations in neural activity affect synaptic and network function and to explore the mechanisms that either promote or impede recovery," said Cope. "The wide array of approaches and expertise that we have as a team is likely to accelerate our understanding because we can attack the problem of limits on regeneration with greater insight and technical expertise than any one of us could achieve alone."
Cutting-edge methodologies will be shared across the five projects. Studies will examine neurons and synapses using electrophysiological tools to evaluate their function. Microscopy and associated imaging techniques will assess structure and changes in protein expression.
"Collaboration with the other team members is critical to placing our findings in the context of functional and structural changes that are occurring in the CNS and PNS after nerves regenerate," adds Dr. Fyffe, Ph.D., associate dean for research affairs.
"Essential details about the mechanisms underlying changes following PNS injury are largely unknown and must be obtained in order to develop clinical applications to many common human conditions, including spinal cord injury," adds Dr. Cope. "How can we get these neural circuits to operate normally, to communicate the way they used to? Our research niche focuses on the limits to recovery after nerve regeneration."
Affirming our goals, our resources and our expertise
"Getting this grant places us in an elite category," says Howard M. Part, M.D., dean for the Boonshoft School of Medicine. "Our team's impressive accomplishment reflects the hard work and dedication of our outstanding scientists, as well as the continued support of our community, especially from The Kettering Fund and from the Oscar Boonshoft family."
Grants received from these sources helped coordinate neuroscience research and recruit additional outstanding research faculty to Wright State. The Kettering Fund has supported biomedical research at the Boonshoft School of Medicine since 1998 and was instrumental in advancing several key research areas at the medical school.
In February, the school announced the formation of a Comprehensive Neuroscience Center (CNC) for improving research of neurological, developmental, cognitive, psychiatric and trauma-induced nervous system disorders. The CNC was made possible through a grant from the Boonshoft Innovation Fund, established when Oscar Boonshoft, a local philanthropist and long-time supporter, gave Wright State University School of Medicine a gift of $28.5 million dollars in 2005. His goal was to provide new resources to spur innovative ideas and programs that would propel the school to national leadership in medical education, patient care and research.
The newly established center integrates teams of scientists and clinicians across several disciplines-on and off campus-to collaboratively address fundamental issues in both basic science and clinical neuroscience research. Actively involved are faculty in the fields of biochemistry, cell biology, molecular biology, neuroscience, pharmacology, physiology, psychiatry, psychology and toxicology.
"The CNC will advance our research of the nervous system at levels ranging from cellular and molecular mechanisms to behavior," said Cope.
"The Program Project Grant has, in effect, affirmed our goals, our resources and our expertise. The vision for this collaborative center is to continue to build upon our core strengths and infrastructure as well as leverage strategic resources," said Part. "We see neuroscience research as a significant growth area and an important component in educating our students and advancing patient care."
The Program Project Grant recently awarded to five Wright State University researchers by the National Institute of Neurological Disorders and Stroke reaffirms that there is strength in numbers in scientific endeavors. It is the power of shared experience, shared expertise, technology, equipment and resources that are at the foundation of a Program Project Grant. Drs. Francisco Alvarez, Timothy Cope, Kathrin Engisch, Robert Fyffe and Mark Rich bring decades of combined expertise to the pursuit of their common interest. Following are specifics about the researchers' five individual projects by which they endeavor to better understand the recovery-or lack of it-from neurotrauma.
Project One: Circuit Plasticity
Timothy Cope, Ph.D.
Professor and Chair, Department of Neuroscience, Cell Biology and Physiology,
Director, Comprehensive Neuroscience Center, Program Project Grant principal investigator
"After nerve damage and regeneration, we lose the stretch reflex in affected muscles, adversely affecting our ability to control movement. We theorize that damage to the PNS creates problems in spinal/neural circuits which do not reverse after nerve regeneration." » More.
"Motoneurons control the activity in our muscles, but their function is in turn modulated by a fine balance between excitatory and inhibitory influences. We suspect that deficits in reacquiring this balance following nerve injury and regeneration are partly responsible for the incomplete restoration of motor function." » More.
Project Three: Synaptic Plasticity
Mark Rich, M.D., Ph.D.
Associate Professor of Neuroscience, Cell Biology and Physiology
"Injury changes how the synapses transmit at the neuromuscular junction and we theorize that reduced cellular activity at the time of injury adversely impacts signaling strength." » More.
Project Four: Molecular Regulation of Release
Kathrin Engisch, Ph.D.
Associate Professor of Neuroscience, Cell Biology and Physiology
"We are examining the underlying molecular mechanism caused by the change of cellular activity. The process at the molecular level indicates that the protein Rab3A plays a major regulatory role." » More.
Project Five: Postsynaptic Excitability
Robert E. W. Fyffe, Ph.D.
Associate Dean for Research Affairs
"Our laboratory will use new imaging techniques to help determine how the excitability and electrical properties of motoneurons are regulated after nerve injury." » More.
Photo: Researchers (left to right) Robert E.W. Fyffe, Ph.D., Timothy Cope, Ph.D., Francisco Alvarez, Ph.D., Kathrin Engisch, Ph.D., and Mark Rich, M.D., Ph.D.