The Scientific Advisory Board of the Conquer Fragile X Foundation includes some of the most well respected scientists, clinicians and practitioners from around the world. They guide the foundation's scientific funding decisions and advance our cause every day. Each issue of the CFXF newsletter features one of our Scientific Advisors and in this issue we proudly spotlight Dr. Gideon Dreyfuss.

Dr. Gideon Dreyfuss, Isaac Norris Professor of Biochemistry and Biophysics, Howard Hughes Medical Institute Investigator, University of Pennsylvania School of Medicine.

Dr. Dreyfuss received his Ph.D. degree in biological chemistry from Harvard University in 1978 and was a Helen Hay Whitney post-

doctoral fellow at the Massachusetts Institute of Technology. Prior to his present appointment, he was Professor and Established Investigator of the American Heart Association at Northwestern University.

Dr. Dreyfuss is chiefly interested in the transport of RNAs and proteins between the nucleus and cytoplasm and in the molecular functions of SMN, the protein responsible for the neurodegenerative disease spinal muscular atrophy.

The research efforts of the Dreyfuss laboratory are presently focused on four interrelated topics:

* The transport of proteins and RNAs between the nucleus and the cytoplasm.

* The molecular function of SMN (Survival of Motor Neurons), the protein product of the Spinal Muscular Atrophy (SMA) disease gene

* The structure and function of the hnRNP proteins, with particular focus on the role of these proteins in the formation and function of mRNA

* Novel phage display methods for identification of interacting proteins.

Two of Dr. Dreyfuss' more recent publications include: Nakielny, S. and G. Dreyfuss (1999) Transport of proteins and RNAs in and out of the nucleus. Cell 99:677-690 and Kataoka, N., J. Yong, V.N. Kim, F. Velazquez, R.A. Perkison, F. Wang and G. Dreyfuss (2000) Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. Mol. Cell 6:673-682

A brief description of these projects include:

Drs. Howard Cedar and Aharon Razin of the Hebrew University of Jerusalem
The role of methylation in fragile X syndrome
"In this project we will use normal human cells and cells from patients with fragile X syndrome to study the dynamics of DNA methylation at the fmr1 locus. Repression at this site is not the result of a direct irreversible mutation in the gene, rather it is due to an epigenetic event and for this reason it is very likely that inhibition may be reversible. Thus, research on this regulatory mechanism could pave the way toward developing new strategies for preventing or even ameliorating this disease."

Dr. Michael Fry of Technion-Israel Institute of Technology Protein-mediated unwinding of secondary structures of the fragile X syndrome expanded sequence d(CGG)n "'Fragile X syndrome, is engendered by dynamic expansion of a d(CGG) trinucleotide repeat sequence at the 5' untranslated region of the FMR1 housekeeping gene. As a result of this expansion, transcription of the FMR1 alleles is silenced and their replication becomes delayed. Reversal of the transcriptional silencing of FMR1 protein may serve as a therapeutic measure to revoke the grave clinical manifestations of the syndrome. Studies from our laboratory and results of other investigators indicate that d(CGG)n tracts readily assume hairpin formations that also assemble to generate multi molecular tetrahelical structures.'…'Results of this study are expected to shed light on potential strategies for the prevention or reversal of fragile X syndrome'".

Dr. Menahem Segal of the Weizmann Institute of Science

The role of fragile x mental retardation protein in the development and functional maturation of spine synapses in vitro
While scientists continue to be puzzled by the lack of an apparent difference between a 'normal' brain and that of a mentally retarded person, new information that points to origins of mental retardation has begun to emerge. The objective of this project is to better understand the role of FMRP in synaptic structure and function in a controlled, in vitro test system involving the tissue cultured neuron. Mental retardation, typical of patients with fragile x, may be manifested by abnormal and malfunctioning synaptic connections.

Dr. Giovanni Neri of the Catholic University in Rome, Italy
This project is based on the fact that in almost all fragile X patients the coding region of the fragile X gene (FMR1) is undamaged but "turned off" by a defect in the region of DNA that regulates the gene. Dr. Neri and his team are trying to reverse methylation and turn the gene back on.

In the coming months and years, CFXF will expand the number of projects it funds and work diligently to develop creative and dynamic links between research facilities and scientists in the US and those abroad, particularly at our partner Israeli sites. Collaboration and cooperation is the most effective path to maximizing all available resources and advancing most rapidly toward a cure for fragile X.

This year alone, we have already had inquiries from Australia and from Spain. The fragile X world at all levels is becoming aware that CFXF is providing significant support to the international research community, not only in terms of project funding, but also as a bridge builder, interested in fostering research partnerships all over the world.