Collaborative seed grant proposals were solicited with the following requirements: involve more than one laboratory and discipline, address a current scientific focus of the Hope Center, have a clear application to research translation, and show promise for subsequent independent funding.

Project 1:
“Misfolded protein accumulation and neurodegeneration due to phospholipase gene mutations”
Paul Kotzbauer, MD, PhD, Neurology
Joy Snider, MD, PhD, Neurology
$90,000

Many neurodegenerative disorders are defined by accumulations of misfolded proteins in the brain. Mutations in the gene PLA2G6, which is involved in lipid metabolism, lead to neurodegenerative disorders and accumulation of alpha-synuclein -- the same protein that accumulates in the brains of Parkinson’s Disease patients. This project will develop methods to detect misfolded protein accumulation in cultured neurons, and will generate a new animal model of alpha-synuclein overproduction. These new tools will enable the development of therapies to minimize toxicity and improve clearance of misfolded proteins.

Project 2:
“Function of FGF14 in progressive spinocerebellar ataxia”
David Ornitz, MD, PhD, Developmental Biology
Kel Yamada, MD, Neurology
Jeanne Nerbonne, PhD, Developmental Biology
David Wozniak, PhD, Psychiatry
$100,000

Patients with spinocerebellar ataxias (SCAs) experience a loss of muscle control in their arms and legs, with resulting loss of balance and coordination. Patients with SCA type 27, a dominantly-inherited condition, have progressive ataxia as well as mental retardation. SCA27 is caused by a single-gene mutation in the gene encoding fibroblast growth factor 14 (FGF14). An animal model lacking FGF14 function shows similar behavior. This project will fully characterize the degenerative phenotype in FGF14-deficient animals. Additionally, these investigators will generate an animal model which more closely resembles the genetics of the human disease, to reveal the molecular mechanisms which lead from FGF14 mutation to degeneration of cerebellar neurons.

Project 3:
“Microdevice development for the study of axon degeneration and injury”
Shelly Sakiyama-Elbert, PhD, Biomedical Engineering
Karen O’Malley, PhD, Anatomy & Neurobiology
Amy Shen, PhD, Mechanical Engineering
$50,000

The axon of a nerve cell functions like a highway, shuttling neuronal components that are necessary for the nerve cell’s survival. An emerging idea in degenerative disorders is that a loss of axon function plays an important role in the initiation and progression of diseases such as in Alzheimer’s, Parkinson’s, or ALS. The overall goal of this research is to design and use compartmented chambers to allow the study of axon growth and function under controlled conditions. These microdevices will allow precisely controlled delivery of drugs or toxins to examine their effects on axon function. Through these studies we will gain a better understanding of factors that contribute to neurodegenerative disorders, and test potential drugs under controlled conditions to determine their effectiveness.

Project 4:
“Development of a Clinically Relevant Mouse Model of Infant Traumatic Brain Injury”
David Brody, MD, PhD, Neurology
Alexander Parsadanian, PhD, Neurology
Philip Bayly, PhD, Biomedical Engineering
Krikor Dikranian, MD, PhD, Anatomy & Neurobiology
$50,000

The human brain undergoes substantial growth and development during the first two years of life. Traumatic brain injury (TBI) during this window is a leading cause of death and disability, and can cause profound alterations of the brain including cognitive dysfunction, attention deficit, hyperactivity and impairment in emotional regulation and judgment. There currently are no effective treatments for TBI other than supportive care, and relatively little research focuses on pediatric TBI compared to other problems of comparable importance. To better understand how infant TBI leads to these behavioral changes, this research project will develop and characterize a clinically relevant mouse model.