The Fragile X Syndrome is caused by transcriptional silencing of FMR1, the gene encoding the RNA binding protein FMRP. FMRP represses mRNA translation in the brain at the level of ribosome transit (polypeptide elongation). We have shown that Fragile X resuce occurs when FMRP knockout (KG) mice are subjected to genetic albation of the transational activator proiten CPEB, the signaling molecule p70S6 kinase 1 (S6K), or inhibiton of PI3 Kinase (PI3K). Moreover, protein synthesis levels, which are aberrantly high in the absence of FMRP, return to normal when CPEB, S6K1, or PI3K are ablated or inhibited. The RNAseq/bioinformatics (RB) core will provide computational analysis of newly developed genome-wide methods to investigate translational control and cytoplasmic polyadenylation in genetically-altered mice. The RB core will also serve as a data hub and standardize analysis for the three projects, and will provide an interface to sequencing facilities for the generation of cDNA libraries and deep sequencing. The RB core will assist the three research projects in data analysis and interpretation. The RB core has devised new computational methods to examine translation homeostasis in disease model mice and in human Fragile X iPS cells.

Public Health Relevance

The Fragile X Syndrome is the most common inherited for intellectual disability and the most prevalent monogenic form of autism. This RNAseq/bioinformatics core is a key part of this Center as it seeks to understand how translational homeostasis regulates the Fragile X syndrome. The Core will provide assistant, insight, and computational analysis assessing Fragile X model mice and human Fragile X IPS cells

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54HD082013-01
Application #
8795349
Study Section
Special Emphasis Panel (ZHD1-DSR-Y (53))
Project Start
2014-09-22
Project End
2019-05-31
Budget Start
2014-09-22
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$250,233
Indirect Cost
$100,840
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655