Children's Hospital of Philadelphia, University of Pennsylvania

URL: http://www.research.chop.edu/programs/iddrc/neurospeccore.php

Keywords Analytical Neurochemistry

Description

The rationale for this core is that neurochemical derangements occur in many developmental disabilities, including metabolic diseases, hypoxic injury, epilepsy, neurotoxicity, etc.

Objectives

• Measure "small molecules" (primarily amino acids and biogenic amines) of  importance to brain chemistry
• Assay stable isotope enrichment with mass spectrometry in order to perform kinetic studies of metabolic flux, both in vitro and in people with developmental disabilities
• Identify and characterize peptides and proteins that are important to neurologic function
• Perform cell-based assays of physiologic processes that are important to brain function, including assays of Ca^2+, calpain, caspase and ROS
• Assist users with regard to experimental design and data interpretation

Services

• Cell-based assays subcore - the focus is in situ visualization of intracellular processes (Ca²⁺, reactive oxygen species and markers of cell death)
• Small molecules subcore - the foci are (a) assay of amino acids and biogenic amines; and (b) assay of stable isotope enrichment to perform kinetic studies of brain metabolite turnover
• Proteomics subcore - the focus is the identification of proteins and their post-translational modifications

URL: http://www.research.chop.edu/programs/iddrc/studydesigncore.php

Keywords Biostatistics and Bioinformatics

Description

The Biostatistics and Bioinformatics Core supports IDDRC researchers in experimental design and biostatistical analysis of data from traditional sources, as well as studies that use genomic and functional genomic data.

Objectives

• Support the needs of the IDDRC investigators in the areas of experimental design, biostatistical and statistical genetics analysis, and bioinformatics
• Offer unique individualized educational opportunities for core users that leverage and complement existing educational programs at University of Pennsylvania
• Engage in the development of new methods needed to address issues in data analysis that are raised by core users

Services

Study Design

• Evaluate feasibility and validity of proposed designs
• Calculate sample size and statistical power and precision
• Advise on the development of appropriate data collection tools
• Support design of new research proposals

Data Analysis

• Provide brief consultations on statistical analyses and on presentation of analyses
• Develop data and analysis workflows for projects requiring significant data integration
• Collaborate fully on the analysis of data
• Integration of genomic and functional genomic data with clinical and public data
• Develop graphs and tables to summarize results for presentation and publication
• Develop new statistical and informatics methods to address issues raised by users' research 

Education

• Raise awareness of training in biostatistical and bioinformatics methods available through the university
• Provide education in statistical and bioinformatics methods for Center members
• Work one-on-one with investigators to reinforce and build on existing levels of expertise

URL: http://www.research.chop.edu/programs/iddrc/cellneurocore.php

Keywords Cellular Neuroscience

Description

An appreciation of cellular physiology and biochemistry is fundamental to understanding the many diseases that are associated with intellectual and developmental disabilities.  The primary goal of this core is to provide IDDRC users with the wherewithal to acquire such information.

Objectives

• Make available a broad array of consultative services and sophisticated techniques to IDDRC users
• Counsel IDDRC users with regard to tissue preparation and cell culture techniques
• Offer IDDRC users novel expertise involving live video-imaging, optical imaging and the generation of human induced pleuripotent stem cells

Services

• Neuropathology
• Cellular Electrophysiology
• Neuronal and glial cell cultures
• Tissue processing and staining
• Tissue microarray and laser capture microscopy

Keywords Neuroimaging

Description

The rationale for the Neuroimaging Core is that the revolution in neuroimaging technology - a landmark achievement of contemporary neuroscience research - enables the in vivo scrutiny of the brain of people with developmental disabilities with a hitherto inaccessible level of detail.  Such information profoundly alters our understanding of these disorders and is essential to the ongoing effort to improve the lives of people who are so afflicted.

Objectives

• Provide in children and adolescents quantitative structural, physiological and functional imaging
• Provide in rodents analogous imaging capabilities by using hardware optimized to yield comparable anatomic resolution, thereby enabling translational interpretations in animal models
• Utilize the technology of this core to develop and evaluate electrophysiologic and imaging biomarkers that better characterize the biologic basis of developmental disabilities
• Utilize such non-invasive and physiologically-specific imaging and electrophysiologic indices to evaluate the efficiency of behavioral and pharmaceutical therapie
• Assist users with regard to experimental design, imaging modality selection, quantitative image analysis and data interpretation

Services

• MEG - the focus is electrophysiologic assessment of brain function and connectivity, emphasizing temporal and spectral attributes
• Magnetic Resonance Imaging - the foci are: (a) structural assessment of brain volumes and grey matter/white matter distribution; (b) physiologic measurements, based on assessments of regional cerebral blood flow, water diffusion, microvascular characterization, and metabolic content; (c) white matter fiber tractography based on diffusion tensor imaging (DTI) and high angular resolution diffusion imaging (HARDI); and (d) functional brain mapping using BOLD fMRI
• PET/CT - the focus of the unit is the use of positron-emitting species to (a) measure regional cerebral blood flow; (b) blood volume; (c) brain glucose and oxygen metabolism; (d) distribution and function of key neurotransmitter receptors and transporters; and (e) identification of salient pathologic features such as amyloid
• Small Animal Imaging - the focus is (a) neuroimaging of animals with methods similar to those used in human studies, a goal being confirmation of animal models as valid surrogates for developmental disabilities; (b) establishing a correlation between the phenotype derived from animal neuroimaging and that drawn from immunohistochemical and/or histologic methods, the latter the "gold standard" of the underlying pathology