Michael J. Mustari - US grants

Our objective is to study the visual and motor contributions made by single units to the generation of primate smooth pursuit. In particular, investigations will be centered in the dorsolateral pontine nucleus (DLPN) where, in preliminary studies, we found units that have visual sensitivity and activity related to smooth pursuit eye movements. Eye movements will be monitored with the scleral search coil technique while recording from DLPN units in behaviorally trained, chronic monkeys. The response properties of DLPN units will be tested during smooth pursuit eye movements and during visual, optokinetic, and vestibular stimulation. The afferent and efferent connections of the relevant regions of the DLPN will be studied using electrophoretic injections of anatomical tracers (horseradish peroxidase and tritiated amino acids). These tracers will be placed in locations where smooth pursuit related units have been recorded. The anatomical findings will guide the future selection of new single unit recording sites. Electrical stimulation of the flocculus will be used to antidromically activate the various DLPN unit types to positively establish the connectivity of particular neurons with the cerebellum. Electrical stimulation of the middle temporal and posterior parietal cortex will be used to orthodromically activate smooth pursuit related DLPN units. This study will advance our understanding of the smooth pursuit system by providing insignt into the procession of information in the cortico-ponto-cerebellar component of smooth pursuit pathway. Our results should be of assistance in the diagnosis and treatment of a variety of disorders in which smooth pursuit is affected.

The overall objective of the proposed research is to study the visual contributions to eye movement generation, with special emphasis on the smooth pursuit and optokinetic systems. We will extend our ongoing work on the role of the dorsolateral pontine nucleus in smooth pursuit to the primate pretectum and accessory optic system (AOS). We will pursue these studies by several different approaches. First, the visual and oculomotor response properties of single units in the pretectum and accessory optic nuclei of the trained monkey will be investigated. Single unit recordings will be conducted in all subdivisions of the pretectum where, in preliminary studies (Mustari and Fuchs, 1988), we found units that discharged during smooth pursuit eye movements and during optokinetic visual stimulation. Eye movements will be monitored with the scleral search coil technique. The response properties of units will be tested during smooth pursuit, optokinetic and saccadic eye movements as well as during visual and vestibular stimulation. We will use microelectrical stimulation in an attempt to elicit eye movements from different sites. Second, small reversible (xylocaine) and permanent (ibotenic acid) chemical lesions will be placed in pretectal nuclei (e.g., nucleus of the optic tract, pretectal olivary nucleus) and the AOS (e.g., lateral terminal nucleus) to assess their potential contributions to optokinetic and smooth pursuit eye movements as well as to the pupillary light reflex. Third, the afferent and efferent connections of all the pretectal nuclei (e.g., nucleus of the optic tract, posterior pretectal nucleus, pretectal olivary nucleus) and AOS nuclei will be studied using very small injections of retrograde and anterograde tracers (horseradish peroxidase, rhodamine beads and tritiated amino acids). These tracers will be placed at locations where we have first recorded and characterized unit response types. Finally, electrical stimulation will be used to antidromically activate identified pretectal unit types from different efferent targets, including the dorsal cap of the inferior olive, nucleus prepositus hypoglossi, vestibular nuclei and oculomotor complex, to reveal the functional connectivity of the pretectum with other visual and oculomotor areas. This study will advance our understanding of the visual contributions to eye movement generation by the pretectum and AOS may assist the diagnosis and treatment of smooth pursuit and optokinetic eye movement disorders.

The overall objective of the proposed research is to study the visual contributions to eye movement generation, with special emphasis on the smooth pursuit and optokinetic systems. We will extend our ongoing work on the role of the dorsolateral pontine nucleus in smooth pursuit to the primate pretectum and accessory optic system (AOS). We will pursue these studies by several different approaches. First, the visual and oculomotor response properties of single units in the pretectum and accessory optic nuclei of the trained monkey will be investigated. Single unit recordings will be conducted in all subdivisions of the pretectum where, in preliminary studies (Mustari and Fuchs, 1988), we found units that discharged during smooth pursuit eye movements and during optokinetic visual stimulation. Eye movements will be monitored with the scleral search coil technique. The response properties of units will be tested during smooth pursuit, optokinetic and saccadic eye movements as well as during visual and vestibular stimulation. We will use microelectrical stimulation in an attempt to elicit eye movements from different sites. Second, small reversible (xylocaine) and permanent (ibotenic acid) chemical lesions will be placed in pretectal nuclei (e.g., nucleus of the optic tract, pretectal olivary nucleus) and the AOS (e.g., lateral terminal nucleus) to assess their potential contributions to optokinetic and smooth pursuit eye movements as well as to the pupillary light reflex. Third, the afferent and efferent connections of all the pretectal nuclei (e.g., nucleus of the optic tract, posterior pretectal nucleus, pretectal olivary nucleus) and AOS nuclei will be studied using very small injections of retrograde and anterograde tracers (horseradish peroxidase, rhodamine beads and tritiated amino acids). These tracers will be placed at locations where we have first recorded and characterized unit response types. Finally, electrical stimulation will be used to antidromically activate identified pretectal unit types from different efferent targets, including the dorsal cap of the inferior olive, nucleus prepositus hypoglossi, vestibular nuclei and oculomotor complex, to reveal the functional connectivity of the pretectum with other visual and oculomotor areas. This study will advance our understanding of the visual contributions to eye movement generation by the pretectum and AOS may assist the diagnosis and treatment of smooth pursuit and optokinetic eye movement disorders.

The visual system requires a stable image for optimal performance. The optokinetic system works in consort with the vestibular ocular reflex to maintain visual image quality during locomotion. In addition, the visual system is served by saccadic and smooth pursuit eye movement systems in foveating either stationary or moving targets, respectively. Our research is directed at studying the neural basis of some of these important eye movement systems. The overall objective of the proposed research is to study the formation of commands for eye movements that occurs in brainstem regions specifically related to smooth eye movements. We will pursue this research by using several different approaches centered around studies in the trained rhesus monkey. Our own studies as well as those of others have demonstrated that the nucleus of the optic tract (NOT) and dorsolateral pontine nucleus (DLPN) play important roles in optokinetic and smooth pursuit eye movements. Using the potent GABA agonist, muscimol, we will unilaterally inactivate the NOT to assess its potential role in the short latency ocular following response and in the initiation of smooth pursuit. To further our understanding of these visually elicited eye movements, we will study the transformation of cortical signals that occurs in the NOT and DLPN to produce smooth eye movements. The response properties of brainstem and cortical units will be tested during smooth pursuit, optokinetic, ocular following and saccadic eye movements, as well as during visual stimulation. Eye movements will be measured with the scleral search coil technique. Electrical stimulation, delivered in the NOT and DLPN, will be used to antidromically activate identified MT and MST units. This will allow us to determine the properties of cortical neurons projecting to the NOT and DLPN. Discrete permanent lesions will be placed in the NOT and DLPN to determine their relative contribution to the ocular following response, optokinetic nystagmus and to the initiation and maintenance of smooth pursuit. Finally, we will perform correlative anatomical studies to further elucidate the anatomical substrate of the visual/oculomotor pathways responsible for smooth eve movements. The results obtained in these studies will advance our understanding of the visual and oculomotor systems. These findings will assist in diagnosis and potential treatment of disorders effecting vision and the oculomotor system.

nervous system; vision; eye; Mammalia;

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to define the information carried in different cerebral-cortical neurons that project to pontine nuclei to produce eye and head (gaze) movements. We are specifically targeting neurons in parietal area (MST) and the frontal lobe (FEF) that have been identified as projecting to the DLPN or NRTP using the technique of antidromic activation. Once a projection neuron is identified we use multi-variate statistical modeling to determine the information carried in each neuron and in populations related to gaze movements. We have discovered that there are major differences in gaze-related signals that travel in FEF-NRTP and MST-DLPN pathways. Setting up a new laboratory at WaNPRC in association with the P.I.'s move from Yerkes NPRC to WaNPRC has been a major part of the progress during the last year. Determining the functional contribution of different nodes in the cortical-ponto-cerebellar system will aid in advancing our understanding of gaze control in health and disease.

DESCRIPTION (provided by applicant): Full visual function depends on the coordinated action of vision and eye movements. We must direct our line of sight on an object of interest so that it will be imaged on the fovea of each eye. Furthermore, to achieve maximum visual acuity and depth perception, we must be able to hold our eyes steady on a stationary or moving target. These important capabilities require appropriate postnatal visual and oculomotor experience. The visual and oculomotor systems are immature at birth and sensitive to injury in both monkeys and humans. When synergistic interactions between visual and oculomotor systems are impaired early in life, strabismus (eye misalignment) and loss of visual function (e.g., amblyopia, stereopsis) occur. These disorders, which affect at least 3% of children born in the United States, are permanent and difficult to treat. Human infantile strabismus syndrome is comprised of impaired gaze-holding, eye misalignment and abnormal smooth pursuit and saccadic eye movement coordination. We have developed effective animal models for studying the development of the visual and oculomotor systems by raising infant monkeys (Macaca mulatta) with either surgical or prism induced strabismus. Our non-human primate model of infantile esotropia syndrome allows us to examine neural mechanisms associated with impaired visual-oculomotor function in strabismus. Our studies are directed at understanding the role of cortical-cortical and cortical-brainstem circuits essential for normal visual-oculomotor function and how these circuits are compromised in disease. During the previous finding cycle, we demonstrated that the pretectal nucleus of the optic tract (NOT) was a likely locus for a common gaze-holding disorder (latent nystagmus) associated with infantile esotropia syndrome. Our current studies indicate that alteration in visual and eye movement signals in the medial superior temporal (MST) area may contribute to defective smooth pursuit of strabismic subjects. Our proposed studies address a significant problem in visual-oculomotor development related to strabismus and development of the cortical smooth pursuit system in health and disease. Our studies are hypothesis driven and use behavioral, single unit recording and modeling approaches to examine the potential role of neurons in MST, frontal eye fields (FEF) and their brainstem targets in normal and pathological smooth pursuit eye movements. Completion of our studies will provide important perspectives that could lead to improved diagnosis and treatment options for developmental disorders affecting vision and eye movements in children. In addition, the strabismic monkey provides important opportunities to uncover fundamental neural mechanisms associated with plasticity in the visual-oculomotor systems. PUBLIC HEALTH RELEVANCE Human infantile strabismus syndrome is a common problem affecting at least 3% of children born in the United States. The abnormal gaze-holding, eye misalignment and asymmetric eye movements of infantile strabismus impair vision. We have developed effective animal models (Macaca mulatta) for studying development of visual and oculomotor behavior and the underlying neural mechanisms associated with strabismus. Our research is important for improving understanding of clinically important disorders effecting children and developing new treatment options.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Normal posture, balance and stable vision are dependent on interactions between the visual and vestibular systems. Studies in this project are directed at defining the neural substrate for normal visual-vestibular gaze behavior. We have published studies that show neurons in FEF and MST play differential roles in gaze and gain control. We have shown that neurons in FEF carry a signal that features eye acceleration for gaze. Finally, we used target perturbatation during ongoing smooth pursuit task to show that most MST neurons play little role in gain control. In modeling studies we have shown that cortical areas FEF and MST play complimentary roles in gaze pursuit. This includes a strong contribution to pursuit initiation and maintenance in FEF and MST respectively. Studies in this project document differential signal processing and capability for gaze control in parallel pathways involving cortical-ponto-cerebellar pathways. This work advances our understanding of sensory-motor circuits that are compromised in disease or injury.

neurophysiology; sensorimotor system; visual cortex; Primates; animal colony;

ABSTRACT Strabismus is a common eye alignment disorder found in 3-5% of children and 3-4% of adults. If left untreated in children, strabismus can lead to loss of stereopsis and amblyopia; the brain silences connections from the misaligned eye, resulting in poor visual acuity. In strabismus, the ocular motor control of eye alignment is unbalanced. One potential cause for this imbalance is disruption of the normal two-way neurotrophic factor communication between the ocular motor system and the extraocular muscles (EOM). Our preliminary and published data show that we can produce strabismus in infant monkeys or improve eye alignment in adult strabismic monkeys. With those neurotrophic factors that were effective, the eye alignment was altered by 8 to 14o. We believe improved treatment efficacy for strabismus will require larger angles of correction to eye misalignment. Gene array and our own data suggest that deficits in neurotrophic factor communication associated with strabismus may involve multiple neurotrophic factors. Thus, to increase efficacy we predict that we need to use a combination of neurotrophic factors. We will test two approaches. First, we predict that combinations of neurotrophic factors that used singly on EOM had a demonstrated ability to alter eye alignment in non-human primates. We will test efficacy of neurotrophic factor ?cocktails? in adult rabbits, and the most efficacious will be tested for the ability to produce a significant eye misalignment in infant monkeys. Second, we predict that blocking retrograde signaling of neurotrophic factors will produce a significant eye misalignment. We will examine efficacy of mixtures of neutralizing antibodies or inhibitory binding peptides to block binding of endogenously produced neurotrophic factors to their receptors. This will prevent retrograde signaling by these factors, which we predict are critical for normal eye alignment. The key for success of these experiments is the use of a sustained delivery approach. One issue that we believe precipitates surgical failure rates is that the change in eye alignment is larger than the ability of the ocular motor system to adapt. There is substantial evidence that there is a significant amount of inherent plasticity possible when slow adaptation strategies are used. Our approach uses a sustained delivery method that releases low doses of neurotrophic factors for 3 months. Our data show that unilateral treatment is sufficient to produce altered eye alignment . In addition, the largest change in eye alignment occurs during the final month of treatment, suggesting that ocular motor system plasticity between brainstem nuclei requires 3 months. This timing agrees with literature showing that visual deprivation period in infant monkeys needs to approach 3 months to produce a strabismus. We will test our most efficacious approach for its ability to correct the eye alignment in adult strabismic monkeys. Our long term goal is to develop effective strategies for modulating neurotrophic factor signaling, whether neuron- or muscle-derived, based on a combination treatment strategy. This will inform future choices for moving this strabismus treatment into human patients, with the ultimate goal of preventing loss of visual acuity.

DESCRIPTION (provided by applicant): Full visual function depends on the coordinated action of vision and eye movements to direct our line of sight so that an object of interest will be imaged on the fovea of each eye. To achieve maximum visual acuity and depth perception, we must be able to hold our eyes steady on a stationary or moving target. If normal innervation fails to develop or is compromised by injury, infantile or acquired misalignment of the eyes (strabismus) could result. In fact, at least 3% of children born in the United States are diagnosed with strabismus every year. Early and appropriate treatment of strabismus is essential to prevent loss of visual function. However, treatment of strabismus remains challenging, partly because we lack a definitive understanding of the etiology of the disease. It is likely that misalignment of the eyes in some strabismics is due to improperly calibrated tonic innervation of individual eye muscles or muscle compartments. Ultimately, eye alignment, gaze- holding and eye movements depend on the quality of oculomotor innervation to different extra-ocular muscles (EOM) and muscle compartments. Recent anatomical work, including some from our respective laboratories, shows that there are at least two separate classes of motoneurons that innervate orbital and global layers of EOM. One class (e.g., A-groups) provides en-plaque endings to singly innervate EOM fibers (SIFs). The other class (e.g., C- and S-groups) provides en-grape endings to multiply innervate EOM fibers (MIFs). Importantly, there are clear differences in the sources of signals in pre-motor structures, which modulate these different classes of oculomotor neurons. Our studies will compare and contrast the functional organization and relative roles of different classes of motoneurons (C- and A-groups) that primarily drive either orbital or global muscle fibers. We will test the hypothesis that proper eye alignment could be achieved by the action of different muscle compartments, which have direct insertion on the eye (global layer) or act indirectly by inserting on the recently discovered extraocular muscle pulleys. We will test the hypothesis that C-group motoneurons play a major role in maintaining eye alignment, gaze-holding and vergence. We will accomplish this by conducting neurophysiological studies in monkeys trained to fixate and track moving targets. We will also conduct complimentary neuroanatomical studies to refine our understanding of some of the premotor sources of signals to these different classes of motor neurons. Completion of our studies could significantly advance our understanding of normal and pathological eye alignment, gaze-holding and eye movements. PUBLIC HEALTH RELEVANCE: Treatment and cure of developmental or acquired strabismus requires advancing our knowledge about how the brain controls eye alignment, gaze-holding and eye movements. Our studies will examine the relative roles of different classes of oculomotor neurons that innervate different eye muscle compartments in the above functions.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Treatment and cure of developmental or acquired strabismus requires advancing our knowledge about how eye alignment and eye movements are controlled at peripheral levels. Our studies will compare and contrast the functional organization and relative roles of different classes of motoneurons (C- and A-groups) that primarily drive either orbital or global eye muscle fibers, respectively. Completion of our studies could significantly advance our understanding of normal and pathological eye alignment, gaze-holding and eye movement associated with strabismus and other disorders.

The Washington National Primate Research Center (WaNPRC) has supported AIDS-related research projects for more than 25 years. These projects are performed at the Western facility, where the vivarium is designed to house nonhuman primates at an ABSL-2 containment level with enhanced containment practices implemented for lentivirus research. The AIDS-related research program is expanding with the addition of new core staff, funding of new projects for existing core staff, and new collaborative efforts between core staff and external investigators. With a projected increase in animal numbers, a need to upgrade cage wash facilities, and a need to expand surgical capabilities for upcoming projects, the University of Washington has committed $5.6 million to expand the vivarium by approximately 2500 square feet at the WaNPRC Western facility, install a new cage-wash/autoclave facility and build a state-of-the-art surgical suite for the support of AIDS-related research. We are requesting additional funding to convert the current surgical area into animal housing and to build out additional area within the expanded vivarium space for animal holding. The proposed animal holding rooms will accommodate 80 Group four (10-15 kg) nonhuman primates, or more smaller animals. The rooms will be constructed in accordance with the recommendations of the eighth edition of the Guide for the Care and Use of Laboratory Animals. The completion of the animal holding space will synergistically complement the institutionally-funded project to upgrade the cage-wash facilities and surgical suite, and will improve and increase our ability to conduct biomedical research, especially AIDS-related research.

DESCRIPTION (provided by applicant): The goal of the proposed project is to maintain and expand a specific-pathogen free (SPF) breeding colony of pigtail macaques (Macaca nemestrina) for the support of NlH-supported research at the Washington National Primate Research Center (WaNPRC). Macaques are a valuable model of human disease and are an essential resource for biomedical research. M. nemestrina possess unique characteristics that make them invaluable, particularly in the study of AIDS pathogenesis, immunology, vaccine development, and vaginal microbicide evaluation. The WaNPRC maintains the only major domestic breeding colony of M. nemestrina. In order to meet the demand for M. nemestrina at the WaNPRC in recent years, it has been necessary to import animals from Indonesia. Even with the importation, it has been a challenge to meet requests for animals for NlH-supported research. We propose over the course of the next four years to expand our domestic SPF breeding colony to a self-sustaining census of 1400 animals which will meet the anticipated demand for M. nemestrina. We will employ two major strategies to meet this demand: Improved management, and importation of breeding animals. M. nemestrina are not as hardy as other macaque species, and have different breeding requirements. We have recently established a breeding facility for M. nemestrina in Arizona that is directly managed by the WaNPRC, and focuses specifically on that species. We anticipate that with this strategy we will be able to reduce mortality and increase fertility, resulting in a net increase in the number of animals in th colony. We will also import a total of 200 M. nemestrina to reach our goal of colony expansion. We will have imported animals tested serologically for viral antibodies prior to shipment and confirm their pathogen-free status with in-house repeated serologic testing. Viral pathogens that interfere with research results (SIV, STLV, SRV) or are a zoonotic risk to humans (McHV-1, also known as herpes B) will be eliminated from the colony by raising uninfected offspring separately from infected progenitors and testing all animals in the colony regularly.

ABSTRACT The Washington National Primate Research Center (WaNPRC) provides infrastructure and research support for a large number of biomedical research projects utilizing nonhuman primates (NHP) as models for human disease. Current housing guidelines, regulations and standards require that research facilities provide social housing for all NHPs unless there are scientific or veterinary exemptions. Many of the research protocols at the WaNPRC allow for social housing and others allow for social interactions at least for a portion of the study without compromising experimental outcomes. Socialization of NHP can be challenging due to several factors and facility constraints. To address the challenges, we have designed an innovative modular caging system that is flexible enough to facilitate socialization of NHP housed at the center. However, there are insufficient numbers of these new modular cages to provide social housing for animals currently on study and for our funded facility expansions. Therefore, this proposal seeks support to purchase additional caging to comply with the new requirements. The new NHP caging will replace old-style cages and provide additional cages for our scheduled renovation of our Western facility and the proposed ARC building. In order to increase our holding capacity and compliance with regulation, we need to purchase many new cages. This grant would allow is to purchase 50 modular stainless steel primate enrichment units (100 cages). The proposal specifically requests the purchase of 27 Group 3 rack units (54 cages) and 23 Group 4 rack units (46 cages). Funding from this proposal would greatly enhance our ability to socially house additional macaques for critical biomedical research projects.

? DESCRIPTION (provided by applicant): The primate visual and oculomotor system allows tracking of small visual objects and large moving visual scenes to support optimal visual acuity and visual motor behavior. We use volitional smooth pursuit (SP) eye movements and reflex-like optokinetic (OKR) eye movements to support visual function. Both classes of tracking eye movements require cerebral cortical processing of visual inputs to create initial commands for eye movements. Volitional SP and OKR behaviors offer important perspectives on neural mechanisms that produce sensory-motor behavior, perception and cognitive processing. Our studies focus on the frontal eye fields (FEF) and parietal cortex (MSTd, MSTl, MT), which have been shown to play a role in SP, OKR and perception. However, the information passed between these areas during tracking eye movements remains unknown. Our studies will address this gap in knowledge by providing the first comparative data on visual, eye movement and task related signals carried in feedforward and feedback pathways between frontal and parietal cortex. We will apply novel computational approaches for data analysis, model the functional contributions of frontal and parietal cortex to tracking eye movements, and finally test the model predictions using electrical stimulation and optogenetic techniques to reversibly perturb signaling in this cortical-cortical network. There are extensive cortical-cortical connections between brain regions but we lack specific information about the role of these connections in complex sensory-motor behavior. Our studies are organized under 3 specific aims to experimental and computational approaches that build on information theory and related statistical methods to account for how different signals (e.g., visual, eye movement) are combined and interact to support purposeful behavior. Our experimental work provides novel neurophysiological data taken from frontal and parietal cortical neurons that we identify as projecting from one brain region to another and 2) the experimental results will be directly compared to simulations developed in computational models of cortico-cortical interaction. Our studies have particular intellectual merit in comparing and contrasting different computational approaches for analyzing frontal and parietal cortical neurons simultaneously. We are developing computational models that are capable of predicting eye movement output using neuronal tuning functions determined experimentally. Scientific: In our study we will extend existing, as well as develop novel computational approaches for analyzing dependencies between neuronal firing and behavior. Advancing our understanding of how different cortical areas interact to support sensory-motor transformation and perception has broad scientific applications in normal and pathological neural systems. For example, white matter lesions commonly seen in the aging brain and in other disorders of cortical-cortical communication are poorly understood. Our studies could contribute fundamental knowledge to advance brain-driven neuronal prostheses. Our work could also improve our diagnostic possibilities for eye movement deficits. Dissemination: Our studies take place at the University of Washington's National Primate Research Center (WANPRC) in Seattle and at the Ludwig-Maximilians-University (LMU) in Munich. WaNPRC and UW are known for excellence in primate neuroscience research. The LMU is ranked among the best German universities. LMU was among the first to establish the Bernstein Center for Computational Neuroscience (BCCN) in Germany. Both of our respective institutions are known as leading centers for research and teaching in neuroscience. The LMU is hosting the Graduate School for Systemic Neuroscience (GSN). The UW reaches out to broader academic community at multiple levels through e.g., the multi-disciplinary Neurobiology and Behavior program and Center on Human Development and Disability (CHDD). Outreach: The PIs are actively involved in their institutions' research and teaching missions. This allows us to provide experimental experience and training for computational scientists in Munich and training in computational research for experimental scientists from UW in Seattle. We provide opportunities for students, postdoctoral fellows and mature scientists through group meetings where results will be presented to a broader audience. The PIs and Co-Is are actively involved in local science and clinical translation.

DIRECTOR?S OFFICE PROJECT SUMMARY The Director?s Office has the overall responsibility for WaNPRC operation. This includes day-to-day management of Center affairs, interacting with University of Washington administrative units. The Director works with a dedicated and expert professional staff heading each major unit of the Center. WaNPRC has Associate and Assistant Directors that head the major units of Primate Resources, Finance, Center Programs, Facilities and Information Technology. In addition, WaNPRC has a Research Liaison to assist the Director and other P.I.s in responding to new funding opportunities. The WaNPRC Director?s Office also receives guidance from internal (Research Advisory Committee) and external (National Scientific Advisory Board, and ORIP) groups on Center policies and strategic planning. The Director?s office provides leadership in developing long- term strategic planning and supporting new scientific initiatives.