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-
SCIENTIFIC ADVISORS
Robert Bauchwitz, M.D.,
Ph.D. Columbia University
New York, NY
Jason Dictenberg, Ph.D. Yeshiva University
New York, New York
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
ON-GOING CFXF SUPPORTED RESEARCH PROJECTS
With your help, CFXF
is making significant contributions to fragile X
research throughout the world. CFXF funds in the
form of competitive grants currently support the
work of Drs. Howard Cedar and Aharon Razin of The
Hebrew University of Jerusalem; Dr. Michael Fry
of Technion-Israel Institute of Technology; and
Dr. Menahem Segal of the Weizmann Institute of Science.
CFXF has also contributed to the work of Dr. Giovanni
Neri of the University Cattolica in Rome, Italy.
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.
