William Brooks - US grants

Symbioses between hermit crabs and sea anemones will be studied to determine the interactions and adaptations that have evolved. Experiments will determine: 1) whether the numbers and locations of anemones on the gastropod shell affect the survival of hermit crabs subjected to predation. 2) whether altering the shell's center of gravity alters the placement of anemones by the hermit crabs. 3) whether hermit crabs will take anemones from another crab more often when a predator is present. 4) whether hermit crabs will select shells with anemones more often when a predator is present. 5) the chemosensory abilities of the hermit crabs towards various predators and the anemone. 6) whether the anemone is protected from starfish predation by being transported with the hermit crabs. Such protection would demonstrate that this association represents mutualism.

9412679 Brooks Hermit crabs possess a soft, coiled abdomen which allows the occupancy of vacated snail shells. Because of crab growth and shell degradation by fouling organisms, locating new, larger shells is a critical component in the natural history of these crustaceans. Hermit crabs can procure new shells in different ways. One mechanisms involves intra- and inter-specific shell exchanges between hermit crabs, which can result in a better shell fit for one or both participants. Another mechanism involves location of injured conspecifics. Specifically, several species of crab respond to factors in the blood or hemolymph of their respective conspecifics. Hemolymph from congeneric and other hermit crabs or brachyurans fails to elicit strong attraction responses. The attractant molecules in hermit crab hemolymph have only been investigated in one species, Clibanarius vittatus; they are less than 1000 D in size and likely peptides. Otherwise, very little is known about the specific chemical nature of the hemolymph attractant or the ubiquity of this response i hermit crab species. A third mechanism for hermit crabs obtaining new shells is by locating snails that are being consumed by predators. Proteolytic enzymes produced by predators of snails trigger the release of signal peptides from the flesh. Hermit crabs respond to these peptides by moving towards the source and waiting for the predator to remove the flesh from the shell ( or directly remove remaining flesh left behind by the predator). It is unclear whether these attractant molecules are similar to those involved in crab responses to hemolymph. Previous studies have also shown that some hermit crab species respond preferentially to certain snail odors. How crabs discriminate between these peptide signals is unknown. In all three mechanisms of shell procurement, the size and fit of the crab's present shell can influence its behavior and response. Perhaps other variables such as presence of symbionts als o influence hermit crab responses. In this proposal, the following topics will be investigated: (1) specificity of responses by hermit crabs to hemoplymph; (2) discrimination of chemical signals by hermit crabs; (3) whether snail cues and hemolymph from crabs are chemically similar molecules; and (4) the role of shell fit, sex, and presence of symbionts in mediating responses to shell availability cues. The results of this study will be significant because peptide-mediated responses involving perireceptors are uncommon. Investigation of this novel system will provide important knowledge to chemical ecologists, as well as behavioral and evolutionary biologists. ***

DESCRIPTION (provided by applicant): This is a request to purchase a 3 Tesla Siemens Verio 32-hannel magnetic resonance imaging scanner. This instrument will facilitate extensive research into the neuroscience of obesity, smoking, Alzheimer's disease, and brain recovery injury at the University of Kansas Medical Center. We have an extremely talented and productive group of qualifying investigators who are supported by an outstanding group of imaging scientists. These individuals have been using an existing Siemens Allegra head-only MRI instrument and made considerable advances. However, this system is based on a >10-year old outdated design, lacks many of the features that are available on state-of-the-art systems, and precludes our sharing our technical developments which are platform specific. Moreover, the existing system is becoming so busy that there is inadequate time available for the many exciting projects that we propose to carry out. Finally, our research program is heavily directed towards neuroimaging studies in obesity - National Institutes of Health focus area. Although we have made considerable progress, we are limited in our ability to scan a considerable portion of this population because of the limited bore size of our head-only Allegra scanner which prevents many obese subjects from taking part in these studies. A new Verio scanner will solve all of these limitations and will allow us to move our research forward and to expand into new areas of research. PUBLIC HEALTH RELEVANCE: The purchase of a state-of-the-art 3 Tesla Siemens Verio MRI research scanner will allow the researchers to carry out vital scientific studies into the brain involvement in obesity, smoking, Alzheimer's disease, recovery from brain injury, and learning. The presence of this instrument will help create numerous scientific and support jobs as well as maintain many others at the University of Kansas Medical Center and at Siemens Medical Solutions USA, Inc. The Siemens Verio scanner is designed to be environmentally low impact: low energy consumption, zero helium boil-off technology, and reduced product mass and plastic parts labeled for recycling so that most materials can be reused.

ABSTRACT: NEUROIMAGING CORE Neuroimaging provides a unique non-invasive capability to explore the structure, function, and metabolism from cells to whole organisms. The University of Kansas Alzheimer?s Disease Center (KU ADC) Neuroimaging Core provides a broad integrated translational imaging approach that combines animal and human magnetic resonance imaging capability complemented by positron emission tomography. These approaches are especially suitable for the KU ADC energy metabolism theme since the Neuroimaging Core brings world-class strengths in magnetic resonance spectroscopy as well as great depth in other imaging approaches. These capabilities have impacted the recruitment of new investigators to the KU ADC, with new faculty members, postdoctoral fellows and graduate students identifying the imaging capability of the KU ADC as being a significant factor in their choosing to move to KU. The Neuroimaging Core will facilitate the KU ADC goal of expanding research into aging and neurodegenerative disorders such as Alzheimer?s disease (AD) by providing investigators with (i) neuroimaging facilities, professional expertise, and advanced education in imaging sciences, (ii) a cohort of well- characterized cognitively-normal (CN) and mild cognitive impairment (MCI) participants with imaging data linked to clinical (Clinical Core) and genetic data (MGM Core), and (iii) new methods that will enable investigators to exploit advanced imaging in their studies. Our specific aims are: Aim 1. Provide an integrated imaging environment with advanced support and training for AD and aging research. The Neuroimaging Core provides approved investigators with state-of-the-art imaging facilities and faculty collaborators and senior scientists who support design, data collection and analysis, and interpretation and publication of results. The Neuroimaging Core also provides specialized training in advanced imaging. Aim 2. Provide investigators with a Neuroimaging Cohort with longitudinal imaging to support and stimulate imaging research in AD and Aging. The Neuroimaging Core is characterizing a sample of the Clinical Cohort with MRI every 2 years. This Neuroimaging Cohort is comprised of CN participants (n>100 amyloid elevated, n>100 amyloid non-elevated) and MCI participants (n>100). Participants will be scanned every 2 years and scans will be analyzed to provide brain and lesion volumes stored in the ADC database. These data are available to investigators to stimulate new research and future grant applications. Aim 3. Develop novel techniques for imaging in AD and aging research. The Neuroimaging Core will develop novel MRI and PET imaging methods, related to the energy metabolism theme of the KU ADC.

Project Summary/Abstract This Administrative Supplement requests one-year of funding to support unforeseen costs associated with the University of Kansas Alzheimer's Disease Center Neuroimaging Core. The Neuroimaging Core's overall mission is to support and stimulate brain aging and AD research by providing investigators with advanced neuroimaging support for all aspects of studies - from conceptualization, through implementation and obtaining the resources needed, to the final reporting. This mission is achieved through three Specific Aims: 1) to provide an integrated imaging environment, 2) to establish an imaging dataset linked to clinical data, and 3) to develop novel methods targeted to research in aging, AD, and neurodegeneration. The optional Neuroimaging Core is integral to the metabolism and energy aims of the KU ADC, which is exemplified by the extensive portfolio of 41 active and 14 pending grant applications that rely on Neuroimaging Core support. However, the P30 funds available to support these activities are inadequate to support the extensive needs of these projects. The requested funds will fund two initiatives: 1) expand infrastructure for our sharable dataset and more rapidly start new projects by increasing the effort of the Core Manager by 50% FTE, and 2) provide one year of funding for a magnetic resonance imaging physicist/programmer who will customize MRI acquisition sequences by implementing a novel acquisition approach developed by University of Kansas scientists affiliated with the Neuroimaging Core. This navigator-echo frequency correction approach will help reduce the amount of imaging data discarded because of excessive subject movement during scanning. These sequences will be used in several grant funded projects and also for acquiring our standard imaging dataset on our Clinical Cohort. These projects are feasible within the one-year timeframe of an Administrative Supplement. At the end of this time we will have substantially improved imaging infrastructure to support investigators in AD and aging as well as a series of imaging acquisition sequences that are optimized for use with elderly and cognitively-impaired participants. These sequences will add to our portfolio of sequences that will be shared with other sites within and beyond the NIA ADC network.

Abstract This proposal requests support for new animal MRI scanner electronics system that will replace an obsolete system and provide dramatically improved capabilities. Once installed, this state-of-the-art system will support research from NIH-funded investigators representing four IDeA State institutions in the Midwest: University of Kansas Medical Center, University of Kansas-Lawrence, Kansas State University, and Pittsburg State University. The upgraded system will also support the research initiatives of six NIH-funded centers: University of Kansas Alzheimer's Disease Center, University of Kansas Cancer Center, Kansas Intellectual & Developmental Disabilities Research Center, University of Kansas Polycystic Kidney Disease Research & Translation Core Center, Frontiers: University of Kansas Clinical and Translational Science Institute, and Kansas State University Cognitive and Neurobiological Approaches to Plasticity (C-NAP) CoBRE Center. These electronics will replace the obsolete (Varian Inc) electronics and gradients that have served our imaging center since 2003. They will provide more accurate pulse sequence timing, faster more powerful gradients with increased duty cycle, more receiver channels and multi-channel receiver coils for increased signal-to-noise characteristics and better shimming. It also will come with many new acquisition sequences that will provide enormous new opportunities for data acquisition across a wide range of biomedical disciplines and organ systems. Moreover, the new console provides an intuitive graphical user interface based on clinical MRI scanner designs which is more user-friendly to operators and will open access to a wider user group including graduate students and post-doctoral fellows since their training period will be dramatically shorter. Accordingly, we anticipate reduced imaging costs to investigators funds. This system will be installed as an upgrade to the existing 9.4 Tesla pre-clinical animal MRI scanner in the University of Kansas Medical Center Hoglund Brain Imaging Center. It will be supported by an outstanding team of imaging physicists and neurobiologists who will collaborate with our Major and Minor Users on study design, imaging protocol development, analysis of data and interpretation of results. We expect this upgrade to quickly result in a dramatic increase in research activity at the University of Kansas Medical Center as well as in the nearby region.

ABSTRACT: NEUROIMAGING CORE In vivo neuroimaging assessment of brain structure, function, and metabolism provides powerful mechanistic data complementary to molecular biomarker data. The Neuroimaging Core mission is to support novel research by lowering the barriers for investigators to a wide array of neuroimaging capabilities. The Neuroimaging Core facilitates the use of MRI and PET imaging by providing initial study conceptualization and design, acquisition and analysis protocols, and assistance with data interpretation, manuscripts, and grant applications. The Neuroimaging Core also develops novel imaging methods which are actively deployed across the ADRC network in multisite clinical trials. Core personnel mentor the next generation of scientists and assist established investigators from other fields to initiate studies into AD, aging, and neurodegeneration. The Neuroimaging Core curates a dataset of shareable images from the Clinical Cohort and investigator- initiated studies and sends summary data to the Data Management and Statistics Core for addition to the curated clinical (Clinical Core), genetic and biomarker (Biomarker Core), and histological (Neuropathology Core) database which is shared with investigators for stimulating further study. During the current funding cycle, these efforts have resulted in collaborations with 26 established investigators and nine K-awardees and support for 73 funded projects resulting in 39 peer-reviewed manuscripts. In the next cycle, we will continue these efforts and add two novel capabilities. Neurovascular imaging will allow explorations of the vascular mechanisms contributing to AD and neurodegeneration, adding a novel imaging ?V? biomarker to ATN(MV). Deep phenotyping will yield novel testable hypotheses from the rich integrated clinical, genetic, behavioral, biomarker and imaging data that our ADRC is accumulating from our Clinical Cohort. We propose three aims aligned with the National Alzheimer's Project ACT (NAPA) themes: Aim 1. Support imaging efforts of existing and future investigators in AD and aging research. The Neuroimaging Core will support design and implementation of new studies, provide secure, accessible image storage, standardized analysis pipelines, and training to apply imaging to ADRD. We will provide standard image-based ATN phenotype data for etiologic diagnosis of the Clinical Cohort. We will promote the use of harmonized imaging acquisitions to increase data sharing between investigators and networks such as SCAN and ADNI. Aim 2. Develop novel imaging techniques for AD and aging research. The Neuroimaging Core will develop new imaging acquisition and analysis techniques and stimulate new research by establishing neurovascular imaging and deep phenotyping as novel new capabilities in the KU ADRC. Aim 3. Share and implement imaging methods and data locally and across the ADC network. The Neuroimaging Core will actively share integrated imaging data, deep phenotyping capabilities, and other novel methods across the ADRC network in support of the full spectrum of preclinical to multisite clinical trials.