Resources and Services

The ADM coordinates a substantial pilot grant program, supported through extensive philanthropic efforts and substantial University support, distributing $400,000 per annum in a highly competitive program designed to promote high-risk high return IDD projects. The Core has established reportage and systematic assessments that continuously scrutinize and evaluate the functioning of the center, ensuring that efficiency and cost-effectiveness are maintained at the highest levels and that the Cores evolve to be fully responsive to changes in technology and systems.

Resources available to the UR-IDDRC Human Phenotyping and Recruitment Core (HPR) resources, are outlined below:

The Department of Biostatistics and Computational Biology (DBCB)
The DBCB has a long record of excellence in methodological and collaborative research as well as in graduate education. Institutional and departmental resources include: a department faculty with multi-disciplinary expertise across the statistical and mathematical sciences; state-of-the-art computer equipment; experienced administrative and IT staff to support research and educational activities of the faculty; opportunities for collaboration with a wide array of research scientists and clinicians; and access to extensive print and electronic collections of statistical texts and journals through the University’s academic research libraries. IDDRC investigators will have full access to the facilities and resources of the DBCB in conducting research associated with the HPR Core or other Cores of the IDDRC.

Research Space
Center for Advanced Brain Imaging and Neurophysiology (CABIN): Through the HPR Core, UR-IDDRC investigators have access to the child-friendly environment of the newly remodeled CABIN for clinical assessment activities.  The Center for Advanced Brain Imaging and Neurophysiology (CABIN) is a 6,000 sq. ft. facility that houses a number of specialized neuroimaging laboratories affiliated with the departments of Brain and Cognitive Science on River Campus and the Department of Neuroscience in the School of Medicine and Dentistry. The facility has recently been upgraded and outfitted with quiet assessment spaces appropriate for detailed cognitive and behavioral assessment.

DBP Neurodevelopmental Research Suite: The Developmental and Behavioral Pediatrics Neurodevelopmental Assessment Suite is dedicated and reserved for the purposes of conducting IDD research and contains five treatment rooms designed for behavioral studies of children with intellectual and developmental disabilities and their families. It is located in a quiet corridor in the Saunders Research Building, home of the Clinical and Translational Science Institute at the UR Medical Center. This facility provides convenient, off-street parking, a comfortable, staffed family reception and waiting area, quiet testing rooms with child-friendly furniture, an observation room with two-way mirror, interview rooms for study teams to meet with parents and guardians, and ample locked storage space for testing equipment and materials. The testing facility incorporates Noldus Observer XT technology that provides the opportunity to collect, analyze, and present observational data for studies investigating specific classes of human behaviors (e.g., spoken language, self-injurious behavior). The DBP Neurodevelopmental Research Suite is one of the two primary assessment spaces for the HPR Core.

Clinical Research Center (CRC): The Clinical Research Center (CRC) was one of the oldest General Clinical Research Centers funded by the NIH, with continuous funding since the 1960s. It is now a component of the CTSI. This space consists of a combined adult and pediatric unit totaling 8,474 square feet in contiguous space. The CRC has two components located within the School of Medicine and Dentistry: an inpatient unit consisting of 4 beds and an outpatient area with 8 rooms to support outpatient procedures/studies. Both units share a staff of skilled nurses experienced in the implementation of sophisticated clinical studies. A primary nurse is assigned to each protocol and is available to work with investigators, their research nurse(s) and study coordinators throughout the course of the study. The CRC encourages and facilitates participation of volunteer subjects through its accessible location and dedicated parking. In addition, studies may be conducted in off-site locations as needed. The CRC expedites protocol initiation through specific training programs, dedicated staff assistance, and the co-location of administrative support functions in the CRC. Other resources available to investigators include a metabolic kitchen, DEXA, two rooms dedicated to muscle function testing and analysis and a room for glucose-clamp metabolic studies. Laboratory services are available including short term storage of samples. Study coordination services are also available for short- or long-term needs. This constellation of accessible support services in a dedicated environment ensures that investigators overcome the challenges attendant to clinical and translational patient-oriented research. 
Affiliated Research Centers

University of Rochester Clinical and Translational Science Institute: The University of Rochester Clinical and Translational Science Institute (UR-CTSI) is the academic home for clinical and translational science at the institution, providing a centralized, integrated infrastructure.

Center for Health + Technology (CHeT): The URMC has established the multi-disciplinary Center for Health + Technology (CHeT) whose mission is to conduct hypothesis-driven, rigorously designed, initial investigations of novel therapeutic interventions for human diseases. This research center is focused on strengthening and augmenting the institution’s capabilities to conduct basic and clinical research projects that advance scientific discoveries to initial human experimentation in a safe and efficient manner, consistent with regulatory oversight. 

Center for Community Health: The Center for Community Health provides consultation services related to community-engaged research. Services are offered to ensure that investigators have support for both project development and implementation in the community.
Recruitment Resources
The UR Batten Center maintains an IRB-approved contact registry of individuals with NCL disorders; this resource will facilitate recruitment of CLN3 disease subjects for the Research Project supported by the HPR Core.
URMC maintains a local registry of volunteers interested in participating in clinical research and clinical trials. URMC investigators have access to this resource along with ResearchMatch, a national registry of research volunteers. Additionally, URMC’s Greater Rochester Practice-Based Research Network supports research engagement through primary care practices in our region. There are currently 85 practices in the network, including 40 pediatric practices, 14 family medicine practices, 17 internal medicine practices, and 4 med/peds practices. The member practices represent more than 150,000 children (80% of Monroe County). These resources will help to facilitate recruitment on behalf of IDDRC investigators by the HPR Core.

The Center for Advanced Brain Imaging and Neurophysiology (CABIN) is the central facility of the TNN, and is housed in the ANNEX building of the University of Rochester Medical Center. Located directly across the street from the Medical Center and 100 yards from the UR River Campus (College of Arts and Sciences, School of Engineering & Applied Sciences), the CABIN serves as a bridge between these two crucial branches of neuroscience research. The building contains dedicated vivarium space for non-human primates, and mouse colonies. The renovated facility is 100% research dedicated and provides an exceptional environment for human subject and animal imaging that will ensure success of the TNN Core in four key areas.

• Accessibility: The environment is pleasant and subject friendly and, as a research center, there is no access-competition with clinical work. Dedicated parking for participants is located <20 feet from the entrance.
• Technology: Scanning and image processing facilities are state-of-the-art, ensuring optimal image quality, imaging speed and access to innovative applications. New high-end supercomputing resources ensure adequate support for data intensive analyses.
• Technical Expertise: The CABIN supports a full complement of MRI expert faculty and staff who will support the work of the TNN Core, from data acquisition through analysis, significantly extending the human resources of the TNN Core, but at no additional cost to the IDDRC.
• Funding: The TNN pilot grant program is administered through the UR-IDDRC ADM core. In order to encourage applications and develop new users, the TNN pilot grant program has a rolling application process.

CABIN Facilities: The CABIN houses a 3T Siemens Prisma MRI on the first floor, along with a room containing a mock scanner for participant acclimatization and fMRI task training, a reception area, four assessment rooms and office space for MRI technologists and technical support staff. The second floor is comprised of lab space for 12 faculty along with associated offices and trainee workspace. A shared conference room, meeting facilities and storage areas are included in the second floor. Offices of the Core Director and his students and labs are all located in the building. The third floor contains the Cognitive Neurophysiology Lab, directed by IDDRC co-Director John Foxe and Co-directed by TNN Co-Director Ed Freedman) houses faculty office space for five lab faculty, three additional cognitive assessment rooms, two acoustically and electrically shielded EEG booths and a dedicated 900 sq. ft. MoBI, VR/AR room. These rooms are each schedulable resources providing access and technical expertise to researchers of the TNN. Throughout the CABIN there is wireless internet access for guests and restricted access for authorized personnel. Drs. Foxe and Freedman are also site-PIs of the ABCD study, which is housed in dedicated space in the CNL. Expertise in high volume recruitment, assessment and MRI scanning in young children gained through this large-scale multi-site study will be shared and extended to TNN researchers to facilitate these functions throughout the core.

The CMI core provides advanced imaging, analysis, and viral vector-based transduction methods to support in vitro and in vivo study of phenomena at the subcellular, cellular, tissue, and whole animal scale.  Equipment resources include:

• Multiphoton Imaging Component: This component provides access to a recently upgraded Multiphoton Laser-Scanning Microscope, as well as two fully outfitted surgical stations for the accompanying delicate surgeries frequently needed for in vivo imaging.
• Confocal Imaging Component: This component provides access to a state-of-the-art Confocal Laser-Scanning Microscope as well as substantial one-on-one guidance for obtaining and assessing high quality, quantifiable image-based data for each instrument.
• Super-resolution Imaging Component: This component provides access to a recently purchased STED microscope accompanied by technical expertise.
• Image Analysis Component: This component provides access to high-performance analysis workstations and software. The core staff assists members with their expertise in image analysis and routinely supports the development of specialized analysis routines.
• Viral Vector Component: This component provides a cell culture and molecular biology suite equipped with plasmid cloning and viral production capabilities. Lentiviral and adeno associated viral vectors are commonly generated in this component although herpes simplex virus, retrovirus and adenovirus can also be produced. Dr. Majewska (CMI core Co-director) and her staff provide consultation, design, testing and support application of viral vectors to manipulate focal and global CNS targets to conduct both loss-of-function and gain-of-function studies in primary cultures and animal models. Staff can also provide guidance regarding the planning and execution of animal experiments, related micro-stereotaxic surgical procedures, and the analysis (molecular, histochemical and in situ) of neural tissue.
• Vivarium: Space is available in one-way and two-way animal rooms equipped for dealing with BSL-1 and BSL-2 hazards. The vivarium also provides fully equipped surgical facilities, and vivarium and veterinary staff are available to provide expertise on animal housing and surgery. The facilities and programs of the Vivarium and Division of Laboratory Animal Medicine are fully accredited by the AAALAC and comply with state law, federal statute and NIH policy.

Equipment:

• Multiphoton Imaging Component: The Multiphoton Core Facility is currently equipped with a state-of-the-art Olympus Fluoview FVMPE-RS Twin Lasers Imaging System which was newly installed in January 2018. The system uses a MaiTai HP DeepSee Ti:Sa laser and an Insight X3 laser as two laser sources which offer a wide range of excitation wavelength for various chromophore options as well as high imaging qualities. The FVMPE-RS system also combines a high-speed resonant scanner with a conventional galvanometer scanner to provide high speed as well as high definition imaging in a single system, flexible for both structural imaging as well as dynamic imaging. The system has four high sensitivity photomultiplier tubes and multiple options of filter cubes specialized for multi-color imaging. The system is also capable of doing large image area tiling and stitching with high speed and resolution. In support of intravital imaging and physiology studies, this component provides two fully outfitted surgical stations with Leica Surgical Dissecting Scopes for delicate surgeries, two Kent Scientific Isoflurane Vaporizers for animal anesthesia, two Transonic System Laser Doppler Flow Meters for blood flow measurements, a World Precision Instruments Pressure Monitor for blood pressure monitoring, and a Siemens RAPIDLAB Blood Gas Analyzer for blood gas and pH measurements.
• Confocal Imaging Component: The Confocal Imaging Core Component houses a Nikon A1R HD laser scanning confocal microscope configured for maximum flexibility to support a diverse set of samples and experimental modalities. The system is well suited for imaging live cells or sensitive specimens via either the high-speed Photometrics Prime sCMOS camera or the laser scanning confocal microscopy (LSCM) 1K resonant scanner. A six-line laser launch with AOTF modulation (LUNV) accommodates a variety of fluorophores and increases the number of variables that can be studied simultaneously. The specific excitation wavelengths are 405nm, 440nm, 488 nm, 514nm, 561nm, and 640nm. The system is equipped with four detectors – two high sensitivity PMTs and two GaAsP detectors to enable spectral separation. Built on a TiE-2 inverted microscope with motorized stage, the system includes a mercury-free SOLA light-engine Ti2 Nikon Perfect Focus System to facilitate stability during time lapse, multiple cycle or large area imaging. The system is also equipped with Total Internal Reflection Fluorescence (TIRF) capabilities, which when combined with the extremely sensitive camera (95% quantum efficiency) allows for single molecule detection and tracking. In addition, the NIS Elements High Content imaging package enables automation of more complex imaging routines and Decon Suite decreases the barrier to downstream imaging processing. Multiple stage holders support imaging of many different slide and well formats, as well as a full stage incubator with CO2, temperature, and humidity regulation. This allows live dynamic imaging, including short- or long-term live imaging studies as well as fluorescence recovery after photobleaching (FRAP), fluorescence resonance energy transfer (FRET), and multiple point time lapse imaging. An in-room Binder Incubator equilibrates cultures for a number of hours prior to transfer to the stage incubator with identical CO2, temperature and humidity conditions.
• Super-resolution Imaging Component: An Abberior Stimulated Emission Depletion Super-Resolution Microscope is available with is configured with 4 excitation (imaging) lasers and 2 depletion lasers. Two STED-quality objectives are available for use on the system as well as two high-quality imaging objectives. The Abberior Instruments easy3d STED system offers variable 2D to 3D STED imaging and aberration correction via adjustment of a Spatial Light Modulator (SLM) and various modules for light dose management to reduce photobleaching and phototoxicity.
• Image Analysis Component: The Image Analysis component provides high performance analysis workstations with multiple image analysis software, including Matlab, ImageJ, Amira, and Imaris.
• Viral Vector Component: The virual vector component comprises a dedicated suite of rooms designated at BSL2+ for viral vector packaging. Two pods connect to a negative pressure antechamber that houses an ultracentrifuge and dedicated -80C freezer for long-term storage of packaged vector.  Each pod is equipped with 6-foot biosafety cabinet, two water baths, and two pair of stacked Forma cell culture incubators. The antechamber also contains two Sorvall S100 Discovery ultracentrifuges as well as a discovery M150SE micro-ultracentrifuge for viral purification. The antechamber is also equipped with two inverted Olympus microscopes with both bright field and fluorescence capabilities. Additional equipment required for vector cloning and titering include a Step One qPCR thermocycler (ABI), Molecular Devices Nanodrop spectrophotometer, an ethidium-free D-Digital Gel Imager (Licor), and the BioTek LionHeart FX (Biotek) Microscope/slide-scanner equipped, 60x air magnification, image-based and laser-autofocus, label-free cell counting, brightfield, color brightfield, phase contrast and fluorescence imaging in four channels.

Neurophysiology

• Multiple custom electrophysiology systems with 32, 64, 128 channel Intan Headstages, Intan Acquisition system, custom head fixed behavior rigs (3). 
• 2 dedicated electrophysiology/ behavior rooms are present, each with 256 channel recording arrays for monitoring social interactions while recording neural activity, elevated plus maze, and operate conditioning chambers. 
• 2 standard Kopf stereotaxic digital systems are available, as well as 3 custom Kopf stereotax for awake behaving experiments. 
• 1024 channel recordings of neural activity occurs through a custom electrophysiology system for monitoring network function at a single cell resolution throughout the mouse brain.  This system is custom built and incorporated into a mouse awake running wheel for monitoring activity while the animal receives visual, auditory, somatosensory, and olfactory stimuli.
• A separate, dedicated behavior room contains equipment and computers to test contextual fear conditioning, Morris water maze, Barnes maze, Lashley III maze, Y-maze, and novel object recognition. A shared small animal room contains the necessary equipment for animal surgery, viral vector handling, perfusion, and brain removal. The equipment consists of two Kopf stereotaxic units, an isoflurane unit for safe animal anesthesia, and a sink/bench station with ample ventilation.
• The Core is located in close proximity and physically located in the University of Rochester Medical Center which also houses the Cell and Molecular Imaging (CMI) Core facility, including an Olympus FV-1000 Confocal Microscope with SIM scanner capable of 2-laser synchronized scanning as well as an Olympus Vanox T Fluorescent Microscope (epifluorescence model), MicroBrightfield Stereo Investigator Software for image analysis, and a Pixcell II Arcturus Laser-Capture Microdissection instrument.

Animal Behavior

• 20 standard mouse operant chambers for measuring a wide range of behavioral functions ranging from learning and memory to, attention, motor functions and motivation.
• 8 modified mouse operant chambers that include retractable levers to facilitate development and implementation of behavioral testing,
• 30 multi-rat operant chambers for both standard and high capacity behavioral testing, a novel object recognition apparatus for mice and one for rats, four non-automated repeated acquisition & performance chambers (RAPC) for mice for learning vs. performance capabilities, and water mazes, Barnes mazes, and radial arm mazes for both rat and mouse.
• Equipment for measures of rat or mouse motor function include:
• ten basic photobeam activity chambers for initial activity screening,
• four advanced Photo beam activity chambers for more detailed locomotor activity assessment,
• four force-plate actometers suitable for measuring locomotor activity, stereotypy and whole body tremor), gait-scan system for fine-grained analysis of motor function, rotarods,
• 12 multi-home cage photobeam monitoring system for measuring general activity under normal or modified living conditions, and grip strength and inverted screen testing equipment.
• Social behavior is assessed in plexiglas chambers specifically built for this purpose or in-home cage contexts which are videotaped and then scored. Data files are provided to investigators in an Excel format.   For all non-automated paradigms, accompanying video recording and scoring software is available and has been validated.
• All behavioral testing is carried out in separate dedicated behavioral testing rooms for either mice or rats as needed.