Model Systems Core

Project: Research project

Project Details

Description

MODEL SYSTEMS CORE PROJECT SUMMARY/ABSTRACT The overall goal of the Model Systems Core (MSC) is to develop, provide, and study PKD-relevant models as well as test therapeutic interventions in order to facilitate the translation of basic research findings of Mayo and non-Mayo investigators into clinical practice. This is achieved using three models, nematode, zebrafish and rodent, which work separately and in an integrated way to advance basic and translational PKD research. By spanning from simple to complex organisms, the MSC incorporates expertise in gene and protein function discovery through forward genetic or non-targeted chemical screens (nematodes), PKD pathway discovery and therapeutic testing in small, easily maintained vertebrates (zebrafish), and anatomical, physiological and pharmacological evaluation of mammalian pathomechanisms (rodents). The core is directed by Dr. Stephen C. Ekker who is a leading expert in genome editing, a key component of new model development. Further, MSC Associate Directors provide expertise in each individual model system. Dr. Jinghua Hu (nematode), Dr. Caroline R. Sussman (zebrafish), and Dr. Jan van Deursen (rodent), assure organism-specific advances in accordance with developing technologies in each field. During its four years, the MSC has fine-tuned its services based on PKD researchers' needs in order to provide maximum functionality. The current service aims are: (I) Generate, maintain and distribute PKD models, (II) Characterize PKD models, and (III) Chemical and therapeutic testing in PKD models. Within each model system, service lines are available spanning these three aims, and PKD researchers can make use of >150 nematode, >10 zebrafish, or >20 rodent knock-out/knock-in/transgenic ADPKD/ARPKD/ciliopathy lines, the majority of which have been developed and characterized in the MSC. In the last funding period these lines were used by 52 investigators to support 106 projects at 22 sites. Projects under development in nematode and zebrafish will allow higher throughput screening of pathways and therapeutics, which can then be tested in rodent preclinical trials, with which we have tremendous experience (>25 trials within the last funding period). The expertise and resources of the MSC are enhanced by expertise and facilities for rodent imaging (Dr. Slobodan I. Macura [Co-Investigator] and Dr. Maria V. Irazabal [Consultant]) and development/characterization of new rodent models as well as execution of preclinical trials (Dr. Katharina Hopp [Consultant]).
StatusFinished
Effective start/end date9/15/156/30/20

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $301,340.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $301,340.00

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