We propose to develop a core facility focused on Synthetic Molecular Probes for In Vivo Imaging (SMP, Core-C). SMP Core-C will provide investigators with novel chemical probes of biological systems and offer fluorescence-based imaging of dynamic aspects of physiology and pathology in living model organisms. This core facility will expand the existing imaging infrastructure at KU by bridging a gap that currently exists between very high resolution imaging of cells in culture and low resolution imaging of fluorescent tracers in rodents. By acquiring modern fluorescence dissecting microscopy equipment equipped with integrated microinjection capability, our investigators will gain new abilities to discover and manipulate dynamic biological processes in small model organisms such as Caenorhabditis elegans (nematode worm) and Danio rerio (zebrafish). This core facility function synergistically with the genomics core facility (Core-B), to identify genes that impact functions of probes in vivo, and with the microfabrication core facility (Core-D), to develop devices for imaging and chemical analysis. This integration will empower faculty to use chemical biology approaches to investigate biological problems. This core facility will provide access to highly qualified personnel with experience in synthetic organic chemistry, biochemistry, microscopy, and computational methods for optimization of biological properties of synthetic molecules. Core staff will facilitate prolse design, synthesis, optimization, conjugation, delivery, imaging, data acquisition, data analysis, and interpretation of digital images and video. Working with the core leader. Prof. Blake Peterson in the Department of Medicinal Chemistry at KU, whose research spans the chemistry/biology interface, investigators will gain access to novel fluorophores and delivery systems optimized for in vivo applications, fluorescent sensors of metal ions, pH, and other physiological processes, and fluorescent probes designed for imaging of tumors in vivo in model organisms. Computational support for the design of probes with suitable spectroscopic and pharmacokinetic properties, data analysis, data management, and data curation will be provided by Dr. Gerald Lushington, the Director of the Molecular Graphics and Modeling Laboratory at KU.
The specific aims of the SMP core are: (1) To design, synthesize, evaluate, and optimize novel fluorescent probes of physiology and pathology for in vitro bioassays and in vivo imaging applications;(2) To provide access to instrumentation for time-dependent visualization of fluorescent probes delivered by microinjection or feeding of model organisms;(3) To offer innovative cholesterylamine-based delivery systems for in vivo imaging applications

Public Health Relevance

C. elegans (nematode worm) and D. rerio (zebrafish) represent two of the best model organisms for understanding the biology of all animals. Because these animals can be easily manipulated and studied alive by fluorescence microscopy, novel fluorescent molecular probes optimized for in vivo imaging of normal physiology and pathology in these models represent powerful tools for elucidating mechanisms of disease. Molecular probes developed through this core facility are likely to have broad utility to a wide variety of investigators.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
1P20GM103638-01
Application #
8461772
Study Section
Special Emphasis Panel (ZRR1-RI-B (01))
Project Start
Project End
Budget Start
2012-07-15
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$297,656
Indirect Cost
$58,701
Name
University of Kansas Lawrence
Department
Type
DUNS #
076248616
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Smith, Brittny R; Unckless, Robert L (2018) Draft Genome Sequence of Lysinibacillus fusiformis Strain Juneja, a Laboratory-Derived Pathogen of Drosophila melanogaster. Genome Announc 6:
Knewtson, Kelsey E; Rane, Digamber; Peterson, Blake R (2018) Targeting Fluorescent Sensors to Endoplasmic Reticulum Membranes Enables Detection of Peroxynitrite During Cellular Phagocytosis. ACS Chem Biol 13:2595-2602
Gujar, Mahekta R; Sundararajan, Lakshmi; Stricker, Aubrie et al. (2018) Control of Growth Cone Polarity, Microtubule Accumulation, and Protrusion by UNC-6/Netrin and Its Receptors in Caenorhabditis elegans. Genetics 210:235-255
Fresta, Claudia G; Chakraborty, Aishik; Wijesinghe, Manjula B et al. (2018) Non-toxic engineered carbon nanodiamond concentrations induce oxidative/nitrosative stress, imbalance of energy metabolism, and mitochondrial dysfunction in microglial and alveolar basal epithelial cells. Cell Death Dis 9:245
Field, Thomas M; Shin, Mimi; Stucky, Chase S et al. (2018) Electrochemical Measurement of Dopamine Release and Uptake in Zebrafish Following Treatment with Carboplatin. Chemphyschem 19:1192-1196
McGill, Jodi L; Kelly, Sean M; Kumar, Pankaj et al. (2018) Efficacy of mucosal polyanhydride nanovaccine against respiratory syncytial virus infection in the neonatal calf. Sci Rep 8:3021
Waters, Renae; Alam, Perwez; Pacelli, Settimio et al. (2018) Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue. Acta Biomater 69:95-106
Saylor, Rachel A; Lunte, Susan M (2018) PDMS/glass hybrid device with a reusable carbon electrode for on-line monitoring of catecholamines using microdialysis sampling coupled to microchip electrophoresis with electrochemical detection. Electrophoresis 39:462-469
Zhu, Qingfu; Heon, Mikala; Zhao, Zheng et al. (2018) Microfluidic engineering of exosomes: editing cellular messages for precision therapeutics. Lab Chip 18:1690-1703
Pacelli, Settimio; Basu, Sayantani; Berkland, Cory et al. (2018) Design of a cytocompatible hydrogel coating to modulate properties of ceramic-based scaffolds for bone repair. Cell Mol Bioeng 11:211-217

Showing the most recent 10 out of 134 publications