The Slack Potassium Ion channel is a Therapeutic Target for Fragile X
With $282,000 in funding from FRAXA Research Foundation, Dr. Leonard Kaczmarek and colleagues explored association of Slack channels with the Fragile X protein (FMRP).
Composition and Localization of Dendritic mRNAs in Fragile X Syndrome
With a $80,000 grant from FRAXA Research Foundation over 2 years, Drs. Smith and Wang are investigating which proteins, as well as the mRNA’s that code those proteins, are dysregulated in Fragile X. They have developed a elegant system to visualize the proteins and mRNA’s and determine where they are spacially in the neuron. This will help to better understand the root causes of Fragile X syndrome and to design targeted treatments.
Basic Mechanisms of Disease and Potential Therapeutic Strategies
With $245,000 in grants from FRAXA Research Foundation, Dr. Stephen Warren and his lab at Emory University studied all aspects of Fragile X syndrome, from the mechanisms of repeat expansion to high-throughput drug screens in the Drosophila model of Fragile X. The Warren lab made the original discovery of the Fragile X gene, FMR1, in collaboration with the Nelson and Oostra labs, and is recognized internationally as a leader in molecular genetics. Recent projects include establishment of induced pluripotent stem cell lines from Fragile X patients, and determination of other forms of mutation in the Fragile X gene, other than the most common trinucleotide repeat expansion.
Role of FMRP in the Regulation of Synaptic Plasticity
With more than $1,000,000 from FRAXA Research Foundation over 13 years, Drs. William Greenough and Ivan-Jeanne Weiler at the University of Illinois uncovered the role of FMRP at synapses, leading to much of the subsequent research on Fragile X syndrome.
Using Fenobam to Reduce APP and Abeta in Fragile X Mice
With a $130,000 grant from FRAXA Research Foundation over 2008-2009, Drs. James Malter and Cara Westmark at the University of Wisconsin studied the relationship between the Fragile X protein FMRP and APP, a protein important to the pathology of Alzheimer’s Disease. APP may also contribute to the pathology of Fragile X, and its major metabolite, Aß, may contribute to abnormal protein synthesis via a positive feedback loop. This project sought to restore normal dendritic protein synthesis in Fragile X mice by breaking into this loop.
FMRP-MAP1b RNA Interactions in Fragile X Syndrome
With a $95,000 grant from FRAXA Research Foundation from 2006-2007, Dr. Mihaela Mihailescu and her team at Dusquesne University studied the relationship between FMRP, RNA sequences, and G quartet structure. Results published.
Electrophysiological, Biochemical and Immunohistochemical Characterization of Kv3.1 in Auditory Brainstem Nuclei in the Fragile X Knockout Mouse
With $80,000 in funding from FRAXA over several years, the Yale University team of Leonard Kaczmarek, PhD showed that loss of FMRP leads to an increased Kv3.1 potassium currents. This change impairs timing of action potentials in auditory neurons (and likely others throughout the brain).
Defining Functional Domains of FMRP and Uncovering its Partners via Large Scale Mutagenesis in Drosophila
With $80,000 in funding from FRAXA Research Foundation in 2005 and in 2006, Dr. Yong Zhang and his team at the Chinese Academy of Sciences developed a way to find genes that suppress the Fragile X gene. FRAXA grants $40,000 (2006) and $40,000 (2005) by Xinda Lin show that FMRP is a widely expressed RNA-binding protein involved in RNA transport and translation. Intensive studies in the last decade have demonstrated that FMRP contains four RNA binding domains, but their actual functions are mostly untested. Meanwhile, a dozen or so protein partners and hundreds of mRNA targets interacting with FMRP have been identified, but again their functions are poorly understood.
Splicing Variations of the Fragile X Gene
With an $80,000 grant from FRAXA Research Foundation from 2005-2006, Dr. David Morris and his team at the University of Washington aimed to understand the variation in distribution and function of FMRP isoforms, sought to identify isoforms of FMRP in mouse brain, and define the expression pattern of these versions of the protein.
Drosophila CYFIP, a Molecular Link Between Actin Cytoskeleton Remodeling and Fragile X
With $130,000 in funding from FRAXA Research Foundationfrom 2004-2006, Dr. Angela Giangrande at the Universite Louis Pasteur investigated the interactions between dendrites, messenger mRNA, and the cytoskeleton in fruit flies, which are a simple yet powerful system in which multiple genes can be manipulated with relative ease.
Genetic and Behavioral Analyses of the dFMR1 Pathway in Drosophila Peripheral Nervous System
With a $160,000 grant from FRAXA Research Foundation from 2004-2006, Dr. Fen-Biao Gao and his team at the University of California studied the relationship between mRNA and FMRP.
Composition and Dynamics of FMRP-Containing RNP Complexes
FRAXA Research Foundation funded a grant of $30,000 in 2005 to Dr. Barbara Bardoni at INSERM in France. The team works on the biochemistry of the Fragile X protein.
Role of MicroRNAs in Fragile X Syndrome
With a $70,000 grant from FRAXA Research Foundation from 2004-2005, Drs. Thomas Tuschl and Neil Renwick and their team at Rockefeller University researched how FMRP interacts with miRNA in order to determine more effective treatment targets for Fragile X syndrome.
Transport, Anchoring and Translation of FMRP-Associated mRNAs
With a $40,000 grant from FRAXA Research Foundation in 2005, Dr. Vladimir Gelfand and his team at Northwestern University studied the mechanisms of mGluR and mRNA and how it relates to FMRP.
FMRP Function in the Xenopus Visual System
With a $75,000 grant from FRAXA Research Foundation from 2003-2004, Dr. Holly Cline and her team at Cold Spring Harbor Labratory studied Fragile X proteins and related mRNA regulations in tadpoles.
Fruit Fly Helps Reveal the Secrets of Fragile X
With a $50,000 grant from FRAXA Research Foundation from 2003-2004, Dr. Bassem Hassan and his team at Flanders University researched how Fragile X fruit flies can help further future studies for Fragile X treatment research.
DFXR and Synaptic Tagging in Drosophila (Fruit Flies)
With a $135,000 grant from FRAXA Research Foundation from 2001-2003, Dr. Jerry Yin and his team at the University of Wisconsin researched memory formation in Fragile X fruit flies. Dr. Yin started his Fragile X studies at Cold Spring Harbor Laboratory before moving to the Waisman Center.
Understanding the Function of Fragile X Protein in Drosophila
With a $105,000 grant from FRAXA Research Foundation from 2000-2003, Drs. Haruhiko Siomi and Mikko Siomi at Tokushima University researched approaches to characterize the Drosophila homolog of FMR1 and its associated molecules, and to identify molecular pathways that are involved in the cellular processes which are affected by the loss-of-function of Drosophila FMR1.
Isolating and Characterizing the mRNAs That Bind FMRP
With $60,000 in grants from FRAXA Research Foundation from 1998-1999, Dr. Robert Denman and his team at the New York State Institute for Basic Research explored how FMRP possibly functions.
Structure of FMRP
With a $68,000 grant from FRAXA Research Foundation from 2001-2002, Dr. Lynne Regan at Yale University studied different protein shapes and how they contributed towards different functions for Fragile X syndrome. Results published.
Identification of Specific RNA Targets of FMRP
With a $70,000 grant from FRAXA Research Foundation from 1999-2001, Dr. Robert Darnell and his team at Rockefeller University made significant contributions towards understanding how FMRP functions and how the brain is affected without it. Results published.
Molecular Interactions Between FMRP and Protein Translation Apparatus
With a $65,000 grant from FRAXA Research Foundation from 2000-2001, Dr. Claudia Bagni focused on understanding the specific molecular interactions which regulate protein synthesis, and how they are altered in Fragile X. Dr. Bagni has moved from the University of Rome to VIB in Leuven, Belgium. Results published.
Transcriptional Regulation of the Fragile X Gene (fmr1) in the Olfactory Bulb
With a $35,000 in grant from FRAXA Research Foundation, Dr. Justin Fallon and his team at Brown University studied systematic mapping of Fragile X granules in developing mouse brains, revealing a potential role for presynaptic FMRP in sensorimotor functions.
Transport of the Fragile X Protein
With a $123,000 grant from FRAXA Research Foundation from 1998-2000, Dr. Alan Tartakoff at the Case Western Reserve University studied how proteins communicate with the brain, how and when FMRP travels in the brain, and how to introduce more antibodies to Fragile X research.