This P30 Core Center includes four Biomedical Research Cores that integrate existing intellectual and technological resources at UAB and MUSC to provide a set of services/resources that will enable innovative investigations in the four thematic areas. The proposed biomedical cores are: 1) Core A: The Hepato/Renal Fibrocystic Disease Translational Resource; 2) Core B: The Engineered Models Resource; 3) Core C: The Cellular Physiology Resource; 4) Core D: The Immunoreagent and Structural Characterization Resource. A brief introduction to each of these Cores is provided below.
Core A: The Hepato/Renal Fibrocystic Disease Translational Resource
The objectives of this Core are:
A unique aspect of this Core is that it builds on established clinical, genotyping, and educational programs and through the P30 mechanism will make these data/resources available to the broader community of interested investigators.
Core B: The Engineered Models Resource
The objective of this Core is to provide investigators with novel model systems for in vivo functional analysis of cystic kidney disease genes (cystogenes). The Core has three aims:
The mouse models generated in this core will also provide important resources for the isolation of constitutive mutant or inducible mutant cell lines/tubules for subsequent in vitro analyses performed by Core C: The Cellular Physiology Resource. Core B has already assembled a wide range of mouse and C. elegans lines with mutations in genes involved in ciliogenesis, MKS, NPHP, and BBS. These lines will provide a unique resource for UAB HRFDCC investigators to explore interactions between disease pathways involved in diverse forms of cilia-related hepato/renal fibrocystic diseases.
Core C: The Cellular Physiology Resource
This Core will provide a comprehensive facility to develop cell line resources and perform state-of-the-art physiological experiments in cells and tissues derived from mouse models of the hepato/renal fibrocystic disease spectrum of disorders. The Core has three aims:
One unique aspect of this Core is the breadth of experimental tools and resources that have been amassed to attack specific problems and questions. Other unique aspects of this Core are the ability to use freshly isolated tissues, produce primary and immortalized cell lines, and develop experimental procedures and techniques that maximize the physiological information that can be obtained.
Core D: The Immunoreagent and Structural Characterization Resource
Analysis of human and genetically-engineered mouse models requires thorough morphological examination of tissues from affected individuals. The objective of this Core is to provide P30 investigators with access to sophisticated, state-of-the-art technology for the detection and characterization of morphological changes associated with the hepato/renal fibrocystic disease spectrum of disorders. The Core has three aims:
The core will have extensive interactions with Engineered Models Core (Core B) to characterize phenotypes associated with the models being established and for generation of novel immunoreagents to ciliary-cystoproteins.