Innovation and an interest in “big data” characterize the three Nicholas Hobbs Discovery Grants awarded for 2015-16, which were announced by Elisabeth Dykens, Ph.D., Vanderbilt Kennedy Center (VKC) director and Annette Schaffer Eskind Chair.
Hobbs Discovery Grants are an annual VKC grant program open to VKC investigators or members. Their purpose is to support multidisciplinary preclinical or clinical pilot studies in preparation for submitting competitive grant applications to federal agencies or private foundations. The program is made possible by the generous gifts of members of the Nicholas Hobbs Society, the VKC donor society.
“Vanderbilt University Medical Center is at the national forefront of collecting de-identified clinical data from its patients, and its database now has detailed longitudinal clinical data for around a million patients” Dykens said. “These data, called BioVU, represent a huge opportunity for advancing research on common and rare genetic and neurodevelopmental disorders. This year two of the three Hobbs Discovery grants involve ‘mining’ these data, a complex undertaking.”
Autism and Schizophrenia
Mark Wallace, Ph.D. (Hearing and Speech Sciences), and Karoly Mirnics, M.D., Ph.D. (Psychiatry) , received a Discovery Grant to mine clinical and genetic data related to autism and schizophrenia, two prevalent psychiatric disorders that are linked to changes in neurodevelopment. Both disorders are marked by significant individual variation in behavior and severity, which suggests a complex interaction between genetic and environmental factors.
“We will probe the data for associations and correlations with biochemical analyses, comorbidities, hospitalization statistics, genotypic and phenotypic data, treatment approaches, and more,” Wallace said. “We will be looking for links that might provide clues into the mechanisms underlying these disorders.”
The project involves a unique trans-institutional research team with expertise in autism (Wallace), schizophrenia (Mirnics), use of BioVU/Synthetic Derivative (Paul Harris, Ph.D., Biomedical Informatics), data mining (Richard Urbano, Ph.D., Pediatrics), combined with expertise in “big data” analytical and supercomputing approaches and access to unparalleled computing resources of the Oak Ridge National Laboratories (Georgia Tourassi, Ph.D., and Rangan Sukumar, Ph.D., Oak Ridge Labs).
Disorders of Glycosylation
Glycosylation refers to the biological process of adding complex sugar chains to proteins or lipids. Congenital Disorders of Glycosylation (CDG) have been identified over the last 15 years. These neurodevelopmental disorders are characterized by intellectual disability, and the mechanisms involved are not understood. Kendal Broadie, Ph.D. (Biological Sciences) is developing several genetic models of CDGs, and his lab has already identified several strong modifiers of outcome in the Classic Galactosemia (CG) disorder state. At the same time, a genomic analysis in Ireland demonstrated numerous dysregulated glycosylation genes in persons with CDG.
In their Hobbs Discovery Grant, Broadie and colleagues will study 20 or more individuals with CDG who have clinical and genomic data in BioVU in order to identify glycosylation gene variants, matched with healthy persons without CDG.
“The gene variants identified will be used to design and to generate matching mutations in the Drosophila model of CDG,” Broadie said. “Our goals are to improve our understanding of causes of CDG at the gene level using the unique resources of BioVU, and to develop an improved Drosophila model based on clinical data, with the long-range objective of developing novel therapeutic interventions. Moreover, findings could impact a broad range of intellectual and developmental disabilities that lack effective treatments.”
In addition to Broadie, project participants are Patricia Jumbo-Lucioni, M.D., Ph.D. (Biological Sciences), Tyler Reimschisel, M.D. (Pediatrics and Neurology), and Tony Capra, Ph.D. (Biomedical Informatics).
Cochlear Implants and Sleep
A cochlear implant (CI) is a small, complex electronic device that provides sound perception to a person with severe to profound hearing loss. Since 2000, cochlear implants have been FDA-approved for use in eligible children beginning at 12 months of age. Implantation while young exposes children to sounds during an optimal period in brain development for speech and language skills.
While children sleep, the cochlear implant microphone, which picks up sounds from the environment, typically is removed or turned off. By contrast, children without hearing loss hear sounds while they sleep.
“We don’t really know about the potential deprivation effects of a child not hearing during sleep,” said Anne Marie Tharpe, Ph.D. (Hearing & Speech Sciences), who will lead a Hobbs Discovery Grant to study auditory processing during naptime in children with cochlear implants.
Tharpe indicated that studies examining the age of implantation suggest that early implantation, before 3 years of age, is highly beneficial to a child’s overall cognitive and behavioral development.
“If this research finds that the additional experience of auditory processing during short periods of sleep is beneficial to cognitive functioning, it could provide the groundwork for future research examining the effects from additional auditory processing during longer periods of sleep,” Tharpe said.
In addition to Tharpe, investigators are Alexandra Key, Ph.D. (Hearing & Speech Sciences), with expertise in psychophysiology imaging; Beth Malow, M.D. (Neurology and Pediatrics), with expertise in sleep research; and Adrienne Roman, Ph.D. (Hearing & Speech Sciences).
For 2015-16, individual grant awards range from $22,500 to $30,500.
“We are enormously grateful to all our Nicholas Hobbs Society members for their generosity, which makes these innovative pilot grants possible,” Dykens said.
Pictured top of page: Vanderbilt’s BioVU DNA databank now contains more than 150,000 unique genetic samples. (Photo Vanderbilt University / Anne Rayner)