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The Life Sciences Project Bulletin
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New Projects in GENE DISCOVERY and FUNCTIONAL GENOMICS from Israel and
the Netherlands |
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No.18
– February 2004 |
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Projects 1.
A
Novel Gene Essential for Brain Formation 4.
Recombinant Antibody Arrays for Functional Cancer Genomics 5.
A
New Technology for Constructing Drug Targets and Developing New Drugs in
Silico 6.
Signature Algorithm For Analyzing Large-Scale Gene
Expression Data 8.
Micro-array technology and cluster algorithm for
characterizing receptor-ligand interactions 10.
Human
DNA Repair in Medical Diagnostics 11.
Functional Polymorphisms in Olfactory Receptor Genes 13.
Diagnostic method for early detection and follow-up of
Schizophrenia 14.
Genetic Testing for Usher Syndrome Type 3 15.
A Novel Erythrocyte Differentiation Factor Advertorials 2. Functional genomics of the antigen
presenting DC 3. Programs
that integrate the proprietary AFLP® and cDNA-AFLP technologies 4. Evogene: accelerating natural evolution processes In the News 1.
Gene Discovery Through Est and Genomic Data Clustering and
Assembly 2.
Technion researchers develop 'glue' to support broken
bones |
Events Guest of honour and
keynote speaker: Shimon Peres Presentations
by Israeli Companies and Universities. Mach Making
Event: Investors, Business Development, R&D and Academic Cooperation. Contact Optin for more information. 15 April 2004, SciencePark
Amsterdam, The Netherlands Plant Biotechnology Symposium 8th European Symposium on controlled
Drug Delivery 7-9 April 2004, Noordwijk aan Zee, The
Netherlands 4-6 May 2004. David Intercontinental Hotel, Tel Aviv, Publish
your projects in the Life Sciences Project Bulletin Projects from the previous
Bulletins For more
information contact Optin’s Director Drs. Jennifer
Peersmann or call +31-(0)70-3643260 For background and contact information per
project contact: Optin’s Life Sciences Manager Drs. Eli
Guetta Coming
up in the next Bulletins: New projects in Gene
& Cell Therapy Sponsors The Embassy of The Netherlands MXCard: Profetional Marketing and Customer Teva Pharmaceutical Industries Ltd Announcements ·
EOI'S for the Sixth Framework |
Projects
To unravel the mysteries of brain development and function, one possibility
is to utilize functional genomic techniques as follows. A gene can be specifically increased or
turned-off to evaluate functional outcome.
In many cases there will be a compensatory mechanism and other genes
will take over. However, there are
essential master genes that are vital for normal development and
function. Utilizing advanced
molecular engineering techniques, our research team discovered a gene that
codes for activity-dependent neuroprotective protein (ADNP) and showed that
it is essential for brain formation.
Turning this gene off resulted in the inability to form a brain in a
developing mouse embryo. This finding
led to the hypothesis that ADNP regulates other important genes and to the
demonstration that a gene associated with stem cell multiplication increases
when ADNP is decreased and a gene associated with brain maturation decreases
following decreases in ADNP. ADNP is
regulated, in part, by the neuropeptide vasoactive intestinal peptide
(VIP). Neuropeptides are short proteins
that transmit information between nerve cells and between nerve cells and
their environment. In this family of
molecules, VIP is intimately involved with the development and proper
function of the brain. However,
blocking VIP function is not lethal, while a blockade of ADNP expression
leads to a lethal outcome. As many
diseases are associated with embryonic malformation, mental and motor
retardation and high risk pregnancies, unraveling gene function will open new
horizons in our understanding of brain activity and will pave the way to new
therapeutics alleviating brain damage and deterioration. To this end, functional fragments of ADNP
were discovered, among them a short peptide NAP that keeps nerve cells alive
against conditions that normally lead to their demise; this breakthrough is
now poised for clinical development.
A new start-up company was founded - Allon Therapeutics, Inc.- which
aims to bring NAP to the clinic. Module networks:
identifying regulatory modules and their condition-specific regulators from gene
expression data
Much of a cells
activity is organized as a network of interacting modules: sets of genes
coregulated to respond to different conditions. We present a probabilistic
method for identifying regulatory modules from gene expression data. Our
procedure identifies modules of coregulated genes, their regulators and the
conditions under which regulation occurs, generating testable hypotheses in
the form regulator X regulates module Y under conditions W. We applied the
method to a Saccharomyces cerevisiae expression data set, showing its ability
to identify functionally coherent modules and their correct regulators. We
present microarray experiments supporting three novel predictions, suggesting
regulatory roles for previously uncharacterized proteins. Applying Functional Genomics For The
Development Of Novel Therapeutic Reagents (Genes And Their Derivatives) For
The Treatment Of Cancer And Other Human Pathologies
Researchers at the
Weizmann Institute have developed a unique screening method for identifying
genes involved in cell cycle arrest, apoptosis, and cellular senescence. The method is based on functional
approaches of cloning genes including gene inactivation and selection of
growth resistant clones. The isolated genes may have enormous importance in
developing anti-cancer therapies since their malfunction is likely to have a
key role in cancer progression. Using this method the researchers have
succeeded in isolating several novel apoptotic genes, which are currently
being investigated for their potential oncogenic activity. Recombinant Antibody Arrays for
Functional Cancer Genomics
The group is developing a strategy that will allow for human
single-chain antibodies (scFvs) to be used as endeavors for the study of
newly discovered cancer-associated gene products, and in particular to
elucidate their intracellular location and primary interacting partners. The
human genome project has revealed a vast number of gene sequences and
expressed sequence tags, many of which are still un-annotated. Thus, the main
goal in the post-genomic era, so-called “functional genomics”, is to identify
and characterize a multitude of gene products and to understand their
function within the intracellular milieu. This overwhelming task calls for
the development of novel high capacity technologies to be used as “tools of
discovery”. Currently, the routine use of DNA microarrays for the analysis of
gene expression profiles at the mRNA level and improved informatic tools to
organize and analyze such data.
However, protein arrays, in particular antibody arrays, as tools for
functional genomics or proteomics studies are still in their infancy. The
group has constructed a very large human synthetic antibody-phage display
library from which they can isolate
human antibodies that specifically recognize the products of newly discovered
genes (for example, we are now studying putative prostate cancer-associated
proteins). The scFv isolation platform is the recently developed DIP
selection approach - a high-throughput method allowing the rapid isolation of
scFvs against any particular target, combined with arrays of immobilized
scFv-CBD (cellulose-binding domain) fusion proteins. These arrays will be
screened simultaneously with recombinant gene products decorated with
different fluorescent dyes, allowing parallel isolation of antibodies against
many target molecules in a short time. The isolated scFvs can be used for
studies of their cognate antigen expression and intracellular location by
flow cytometry and immunofluorescent staining of cancer cell lines and tissue
sections, and for co-immunoprecipitation of their antigens in complex with
interacting proteins followed by chromatographic separation and MALDI-TOF
analysis. The results should demonstrate the utility of scFv antibodies and
fusion proteins as invaluable reagents for functional genomics and for cancer
detection. A New Technology for
Constructing Drug Targets and Developing New Drugs in Silico
This novel computerized
technology provides a basis for a multitude of solutions to the most complex
problems of Structure-Based Drug Design, such as the construction of
identified protein targets from their sequence, flexible docking of drug
candidates, protein-protein interactions, de novo construction of drug
candidates from fragments, molecular comparisons, construction and analysis
of combinatorial libraries, analysis of structure activity relations,
ADME/Tox properties and construction of “drug like” libraries, as well as others.
It is capable of considerably reducing the amount of time required to develop
new drugs or to improve drug leads, at all phases of drug development,
thereby decreasing time to market. The core of this new technology is a novel
stochastic search method that has no roots in any previous method and can be
applied to problems of complex combinatorial nature. In addition to finding
the best solution, it identifies many alternatives (“many needles in a
haystack”) that are close to that best solution, i.e., a “population” or
“ensemble” of best solutions. The algorithm is highly efficient and
parallelizable, thus enabling to solve ever-increasing sizes of complex
combinatorics. This technology seems to be unique in its generic ability to
find both the optimal solution and a large set of best solutions or
alternatives. Thus, it could produce “libraries” of drug candidates with
optimized, “drug like” properties. There is currently no similar generic
technology known to us. Signature Algorithm For
Analyzing Large-Scale Gene Expression Data
Signature Algorithm For
Analyzing Large-Scale Gene Expression Data Technologies that
monitor genome-wide expression data are becoming a central tool in biological
research and drug discovery. Researchers at the Weizmann Institute have
developed an algorithm for extracting transcription modules from large-scale
data. This method offers a novel and more informative approach for analyzing
large-scale gene expression data, which enables identifying gene clusters,
which are co-regulated under specific conditions. Identification of Anticancer
Drugs for Patients with Aggressive Breast Cancer: The Synthetic Lethality
Screening Approach
The classical mechanism-based anticancer drug target identification approach
aims at understanding the molecular alterations that drive the malignant
process, and developing selective drug therapies accordingly. Thus, the
current search for cancer therapeutics focuses on either inactivating the
identified cancer-causing oncogenes or reactivating cancer fighting, tumor
suppressor genes. In contrast, the synthetic lethality screening approach
addresses the possibility that some activated oncogenes and mutated
tumor-suppressor genes may sensitize cellular targets that do not necessarily
have abnormal expression in the tumor context. Compounds inhibitory to such
‘secondary targets’ are specific to a particular tumor because they become
lethal only when linked to the previously defined primary alteration in the
cancer cells. Synthetic lethality screens are unbiased in the sense that no
prior knowledge of the identity of the secondary target is necessary. This is
in contrast to the mechanism-based approach that prejudges the identity of
the ‘best’ drug target. Therefore, synthetic lethality screens are likely to
broaden the range of drugs and drug targets that one can find, and shorten
the time required to identify such drugs. Previously, we established the
principles of a chemical synthetic lethality screen in cultured human tumor cells,
and in mouse embryo fibroblasts derived from knockout mice. We have also
established a methodology for a genetic synthetic lethality screen in
cultured human cells. Over the past
two years, we have applied the chemical screening methodology to human breast
carcinomas. This has resulted in the identification of compounds that (at the
sub-micro molar range) specifically kill cells derived from aggressive human
breast carcinomas. Currently, we are seeking investment and/or collaboration
for further development of these potential anticancer drugs. Keywords:
anticancer drug discovery; chemical and genetic synthetic lethality screens;
drug targets; cancer therapy; breast carcinoma. Micro-array technology and
cluster algorithm for characterizing receptor-ligand interactions
Arrays of genes have been characterized
and studied using "DNA chips" designed to detect hybridization
between defined probes and unknown ligands. Researchers at the Weizmann
Institute have extended the concept, technology and analytical tools to deal
with arrays of additional binders, such as antibodies-antigens,
lectins-ligands, and so forth. By applying a particular cluster algorithms
developed by the scientist, It is now possible to classify the state of
health or disease of persons, or the identity of unknown molecules on the
basis of the global patterns of interactions between test ligands and arrays
of probe molecules. Development of Novel
Potassium Channel Openers for Neuroprotection, Neuropathic Pain and the
Treatment of Epilepsy
We are developing a platform for new highly targeted
and genotype-specific therapies. Our aim is to develop specific drugs
(openers) that will enhance KCNQ potassium channel activity, with therapeutic
impact on epilepsy, neuroprotection and cardiac long QT syndrome (LQTs).
Previously, we succeeded in rescuing the loss of channel function produced by
specific LQT mutations by means of KCNQ1 potassium channel openers (Abitbol
et al., 1999). Recently, we have found that openers activate KCNQ2/3
channels, by causing a profound leftward shift of the voltage activation
curve and slowing the deactivation kinetics. This opener action leads to
increased KCNQ2/3 current amplitude at physiologically relevant potentials
and as such these compounds constitute anti-epileptic and neuro-protective
drug candidates. Using rationalized targeted chemistry and high throughput
technology, our drug development strategy is to design and screen for KCNQ
channel openers that will protect from LQTs and epilepsy. A rational
structural chemistry and mutational analysis should facilitate the design of
openers that will correct efficiently genetic abnormalities produced by
specific potassium channel mutations as well as non-inherited cardiac and
neuronal defects of various etiologies. Exploiting the tremendous power of
genetics and structural chemistry, this strategy offers new therapeutic
perspectives in the treatment of epilepsy, ischemic stroke and inherited and
drug-induced LQTs, as well as in the treatment of neuropathic pain. Human DNA Repair in Medical
Diagnostics
DNA damage interferes
with the essential function of DNA by causing it to issue incorrect coding
instructions or by stopping the decoding process. These problems are usually
avoided by DNA repair, a housekeeping process by which the damage is
recognized and repaired by a large battery of repair proteins. Failure of DNA
repair has serious consequences on health causing cancer, immunodeficiency,
infertility, neurodegeneration, and aging. The Weizmann Institute of Science
group has developed a human blood test for a particular type of DNA repair.
This accurate and highly reproducible test measures the enzymatic activity of
the DNA repair in white blood cells. It provides means to predict the
patient’s response to certain treatments and thus aids in selecting and
tailoring the appropriate therapies for malignant diseases, neurodegeneration
diseases and infertility treatment. Functional Polymorphisms in
Olfactory Receptor Genes
It is well known that
human beings exhibit high variation in their olfactory faculties. This
phenomenon is mainly reflected in inter-individual differences of threshold
sensitivity towards specific odorants and variability in odorant perception.
These differences originate from the genetic polymorphism within the
population. Researchers at the Weizmann Institute have identified a family of
Olfactory Receptor (OR) genes and pseudogenes which display a very diverse
repertoire in each individual. This repertoire is greatly influenced by the
ethnic background. The researchers propose a DNA chip of the complete human
functional OR gene repertoire in order to identify specific receptors for
specific odorants for rational design of odors, flavors and perfumes. Recombinant Fragments Of the
Human Acetylcholine Receptor: Application for the Treatment of Myasthenia Gravis
Myasthenia gravis (MG)
is a human autoimmune disease characterized by muscle weakness and
fatigability. In this disease, antibodies against the acetylcholine receptor
(AChR) bind to the receptor and interfere with the transmission of signals
from nerve to muscle at the neuromuscular junction. A diagnostic test for
anti-AChR antibodies in MG has been developed by researchers at the Weizamnn
Institute, that employs recombinant fragments of human AChR as the test
antigen. Such a test would avoid the need to extract the antigen from human
tissue, could yield anti-AChR titers that are well correlated with disease
severity, and may enable to evaluate additional antibody specificities that
are involved in myasthenia. Diagnostic method for early
detection and follow-up of Schizophrenia
Schizophrenia is a
neuropsychiatric disorder afflicting about one percent of the population. It
is characterized by delusions, hallucinations, disorders in organizing
thoughts logically, and emotional withdrawal. To date, a definitive diagnosis
of schizophrenia requires six-month duration of symptomatology and there is
neither an effective biological marker for identifying schizophrenia nor an
accurate and rapid diagnosis to ensure more optimal management at an early
stage in the illness. Researchers at the Weizmann Institute have developed a
method for early detection of Schizophrenia, which is based on measurements
of mRNA levels of D3 dopamine receptor and of α7 nicotinic acetylcholine
receptor (α7 AChR) in peripheral blood lymphocytes (PBLs). The researchers
have shown that individuals suffering from Schizophrenia disorder have
significant elevation of D3 dopamine receptor mRNA and decreased levels of α7
AChR mRNA compared to normal individuals. This method can serve as an
efficient tool for diagnosis and follow-up of Schizophrenia and other
neurodegenerative disorders. Technology
Genetic Testing for Usher
Syndrome Type 3
Researchers at the
Weizmann Institute of Science have located three new mutation linked to Usher
Syndrome Type 3 (USH3), a genetic disorder which causes a postlingual progressive
hearing loss. These mutations are located in the coding region of a newly
identified transcript of human USH3A. The USH3A protein is a member of a new
four trans-membrane domain (4TM) vertebrate- specific protein family. Based
on sequence similarities to stargazing, a well studied member of this
hyperfamily, the researchers have suggested a role for the novel protein in
the hair cells synaptic junctions. A Novel Erythrocyte
Differentiation Factor
Researchers at the
Weizmann Institute have identified a gene encoding for a novel erythrocyte
differentiation factor designated Codanin-1. The protein was shown to be
involved in the differentiation of red blood cells. Mutations in the
differentiation factor are associated with Congenital Dyserythropoietic
Anemias (CDA), a group of inherited red blood cell disorders associated with
dysplastic changes in late erythroid precursors. Nucleic Acid Fragmentation
in Millisecond Time Scales By Conventional X-Ray Machine: Application To Protein-Nucleic
Acid Footprinting
Mapping the interaction
between protein and nucleic acid in physiological buffers and in a dynamic
way provides means for rapidly screening DNA-drug interactions, RNAi
interactions, and protein-DNA interactions. Researchers at the Weizmann
Institute have developed simple, inexpensive procedures of conducting X Ray
footprinting to produce protein-DNA protection portraits at sub seconds time
scales. These procedures could replace high-resolution footprints produced by
Synchrotron Radiation which are expensive and demand complicated logistics. Advertorials Health-Invest: The New Dutch
magazine for Life Sciences
Health-Invest is a new
magazine with popular scientific articles about the newest developments in
Life Sciences in The Netherlands: health, new medicine and food. The magazine
also includes fashion, carrier and financial business. Health-Invest wil
highlight various subjects through combining Life Sciences and Life Style.
Attention wil go to stormy
developments in the medical sciences, for innovative medical research and
company profiles, as wel as developments in the general health and prosperity
of society. Health-Invest is a Dutch language, internationaal orientated
magazine about health and prosperity made for a large audience: from starters
in Life Sciences, to those interested in health-care, the food sector,
students, and especcially investors and eveyone interested in his own health.
The next issue of Health-Invest will come out in January 2004 and wil focus
on: Nanotechnology Nanotechnology is
today seen as the most important industrial revolution of the 21st century.
In the next 25 years an enormous market will develop for products made with
the help of this technique. Besides the information technology the medical
profession wil also profit from nanotechnology. Our body is made up of cells
and a technology that works on that level is much beter suited for treating
sick cells than the treatments now available. The Netherlands has in this
area a very good starting position in order to become an important partner in this enormous nanotechnology
market. Health-Invest will focus
further on this issue. For more information
contact: www.health-invest.nl E-mail:
info@health-invest.nl Functional genomics of the
antigen presenting DC
Dendritic cells (DC)
are the professional antigen presenting cells (APC) of the immune system that
instruct and control the activation of B and T lymphocytes, the mediators of
specific immunity. Their extremely potent capacity to initiate and modulate
immune responses is currently exploited by many groups to fight infectious
diseases, cancer as well as autoimmune diseases. Although much progress has
been made in understanding the DC’s ability to initiate and modulate immune
responses, surprisingly little information is available regarding its
molecular basis. In the past 5 years we have conducted a major effort to
identify a panel of novel DC specific molecules. We selected novel DC
antigens based on two main criteria; I: their preferential expression by DC
and II: their conservation in higher eukaryotes, indicative for an important
function in DC immuno-biology. These novel antigens include a transcription
regulator, DC-SCRIPT; a multi-membrane spanning receptor, DC-STAMP; and a
novel adhesion receptor, DC-SIGN. We
have generated a DC yeast two hybrid library using both mature and immature
DC as a source of RNA to detect potential DC-specific partners. Several
interesting partners have now been defined. These and novel antigens defined
in additional yeast two hybrid screens are the topic of the current research
project. Next to assigning the molecular partners to a given molecular
pathway, the focus will be to unravel their
function in DC immunobiology. For more information
please contact dr G.J. Adema or
prof.dr. C.G. Figdor, phone 024-3617600. E-mail: g.adema@ncmls.kun.nl and c.figdor@mailbox.kun.nl. The Cuppen research group
The Cuppen research group is part of the Netherlands Institute
of Developmental Biology also known as the Hubrecht Laboratory. The institute
falls under the auspice of the Royal Dutch Academy of Arts and Sciences
(KNAW) and is located on the campus of Utrecht University in Utrecht, The
Netherlands. The research in the Cuppen lab is focussed on the functional
analysis of animal genomes (functional genomics), using both bioinformatics
and biological experiments in model organisms. For more information
please contact Dr. Edwin Cuppen ecuppen@niob.knaw.nl or tel. +31 30 2121969 Functional Genomics Group, Netherlands Institute for
Developmental Biology / Hubrecht Lab, Uppsalalaan 8, 3584 CT Utrecht, The
Netherlands. Fax: +31 30 2516554,
Web: www.rat.niob.knaw.nl Programs that integrate the
proprietary AFLP® and cDNA-AFLP technologies
During the last 14
years, Keygene has been very successful in developing the AFLP(r) molecular
marker system and a wide range of related services for (plant) breeding
companies. Their shareholders and main customers have become market leaders
in several high-yielding vegetable crops the last years. Most of Keygene
services are based on AFLP(r), the most cost effective marker technology
available. For many crops Keygene executed large programs and assisted in the
development of extensive genetic knowledge for their customers. For instance;
in Capsicum, Barley, Corn and other species large integrated genetic maps are
build. Keygene can be divided
into two major departments, the first, Gentics, is specialised in services
like identification of varieties, marker assisted back cross programs, marker
development projects (mono- and polygenic traits), genetic (fine) mapping,
allele / chromosome haplotyping and development of specific breeding tools
like mentioned in our article "Breeding by Design(tm)" which
describes the potential possibilities of markers in breeding. Please contact Keygene to receive more information regarding this
revolutionary concept. Keygene Genomics, the
second department, is specialized in innovative contract research. With
in-depth vision and extensive research facilities Keygene Genomics provides
state of the art contract research programs with emphasis on structural and
functional genomics. Programs that
integrate the proprietary AFLP® and cDNA-AFLP technologies with a broad
spectrum of other genomics tools, Keygene Genomics offers total genomics
solutions to its customers. Application of the powerful technology platform
in many different sized programs is now targeted towards the generation of
marker (AFLP®/SNP) sets, gene isolation and the elucidation of complex (QTL)
biological questions. In summary Keygene
offers companies in the life science industry a wide range of services for
the development of specific breeding tools, genetic software packages and
genetic contract research for more complex genetic problems. For information please
contact Arjan van Steekelenburg avs@keygene.com
or tel: +31 317 466 866 Evogene: accelerating
natural evolution processes
Evogene is an
agro-biotechnology company specializing in the development of superior crops
through genome remodeling. Evogene’s
core technology platform mimics and accelerates evolutionary processes and
can address issues associated with transgenic plants. The company has
demonstrated its technological capabilities in Arabidopsis and the tomato and
is currently expanding its platform to other economically significant crops
such as cotton. With a growing base of intellectual property and
collaborative agreements, Evogene’s goal is to emerge as a leading developer
of plant-based products and technologies that have the potential to
accelerate discovery processes.Integrating genomics tools and advanced
breeding to bring plant genomics to the crop in the field. Directing
evolution to generate new genetic diversity. Accelerating the development of
high-value crops and plant-derived compounds. Accelerating and Directing
Natural Evolution: Evogene’s central concept is to develop a platform that
mimics, directs and accelerates evolutionary processes in plants to
circumvent the limitations of genetic variation occurring in classical
breeding techniques. The Evogene Process: By
applying computational and biological tools to public or private plant genome
databases, Evogene predicts, isolates and prioritizes genomic component
candidates associated with specific functions or traits and validates them
in-plant. Evogene believes and demonstrates that optimizing gene regulation
is essential to successful agro-biotechnology development and develops a
strong position in gene regulation and in the optimization of coding region
expression. Evogene uses molecular tools and techniques, with unprecedented
efficiency, generating novel INTRAGENIC genetic diversity within the gene
pool of a targeted crop. Advanced high throughput breeding techniques are
used to bring superior traits to the final plant, successfully addressing the
classical bottleneck between plant genomics and the field. Advanced Predictive
Computational Genomics Skills: Based on the technology used by Compugen’s
pharmaceutical customers in human genomics, Evogene has developed advanced
computational genomics skills to predict and isolate sets of high quality
gene and promoter candidates that address customer-specific problems. This capability provides a solution for
what is currently a major bottleneck slowing product development timetables. ProMine “Promoter Mining” Focusing on Gene
Regulation Optimization: First applied to Arabidopsis, ProMine, a unique
promoter mining tool, was used to generate a library of thousands of
predicted DNA Regulatory Elements (DREs).
Hundreds of these DREs are already biologically validated. By defining partner-driven queries,
Evogene is capable of generating highly targeted sets of DREs to jointly
optimize the expression of a specific coding region. Evogene is developing similar promoter
assets in other economically important crops. “EvoXellerator”: Creating novel INTRAGENIC Genetic Diversity:
The “EvoXellerator” (Evolution Accelerator) technology is a novel approach to
creating new genetic diversity by mimicking and accelerating natural
evolutionary processes while addressing concerns regarding transgenic GMOs
and avoiding limitations inherent in sexual reproduction. HTP: High Throughput Breeding: Initially
implemented in the tomato and currently being expanded to other crops,
Evogene uses miniature plants and other advanced breeding tools to increase
the output of classical breeding techniques.
Evogene applies its High Throughput Breeding to rapidly identify
desirable traits generated by its Evolution Accelerator technology. In addition, Evogene’s High Throughput
technology can deliver breeding projects in a shorter time and at lower cost
than via traditional techniques. In order to implement
its fully integrated approach, Evogene has created a proprietary Information
Management System to track and enhance the vast amount of data generated when
merging computational biology, molecular biology, plant transformation, plant
genetics and classical breeding. This database manages the knowledge created
in the development process, from the DNA sequences in-silico and all the way
to the plant in the field. These products, as well
as others in the company’s development pipeline, are available for licensing,
R&D collaborations and strategic partnership opportunities. For more information
please contact Julien Meissonnier julien.meissonnier@evogene.com or tel: 00 972 8 9311900 In the News Gene Discovery Through Est
and Genomic Data Clustering and Assembly
Of the estimated
150,000 human genes, only a fraction are currently known, and an even smaller
fraction is well annotated (i.e. significant information is known about the
gene function). On the other hand, a lot of low quality, fragmented data
about many of the genes has been collected in the past few years in EST
(Expressed Sequence Tags) databases. Compugen has developed a unique
technology to identify as many new genes as possible, out of this data, and
annotate them in a comprehensive manner, revealing information about their
function, expression patterns, location in the genome and interactions with
other biological entities. Clustering and Assembly: This vast amount of data
is obviously a valuable source of information for life science researchers.
However, the poor quality is a significant hurdle for potential users. It is
first necessary to process the data, bringing together different ESTs which
represent the same gene, and creating a better picture of this gene. Detect SNPs (Single
Nucleotide Polymorphisms): Map gene structure (exons, introns, alternative
splicing) In order to achieve all
this, two different tasks must be performed. The first, clustering, is a
division of the body of ESTs into many different groups, each representing
one gene. The second task, assembly, is using the sequences in each of these
groups to build a comprehensive picture of what is known about this gene.
From multiple ESTs spanning the same region one can then detect and correct
sequencing errors and polymorphisms, and build a gene map. The resulting
sequences are much longer than the input ESTs, and their number is
significantly reduced. Processing the data in this manner makes the resulting
database much more suitable for data mining and annotation. However, both
clustering and assembly pose a significant challenge in algorithmic
development. In clustering one should in principle compare every two ESTs to
each other, in order to decide whether or not they originate from the same
gene. On a 2.5 million EST database, this task literally takes years on a
general purpose computer, even if one chooses to use a heuristic approach
such as BLAST. The assembly problem is different: here the difficulty is in
modeling correctly the underlying biological processes, so that the algorithm
will produce relevant biological information. A good example is alternative
splicing. This biological phenomena, now believed to occur in 30% of all
human genes (see http://hattrick.lbl.gov:8888/alt ), means one gene can
elicit several transcripts, made out of different exon combinations. An
assembly program which neglects to model this phenomenon will be unable to
create one parent sequence which explains multiple ESTs arising from the same
gene but diverging into different variant EST sequences, and will have to
classify them into different genes, yielding a wrong biological answer, and
resulting in significant loss of information. Compugen has developed
novel algorithms for both clustering and assembly, using the expertise
accumulated in the company from years of research into sequence alignment,
biological modeling, and hardware development. The New algorithms developed
allow for the clustering and assembly of millions of ESTs within a few days,
while correctly modeling a wide variety of biological phenomena including
alternative splicing, chimeric sequences, repeats and contaminations of many
types. Compugen has pioneered
the integrated analysis of genomic and expressed data, as well. Genomic data
is clustered together with EST and mRNA data, often providing the missing
information for the discovery of new genes. The algorithms are run on a
periodical basis and allow for reclustering and assembly from scratch of the
full database. The resulting gene database then undergoes a series of
annotation processes, including sequence homology searches, profile searches,
alignment to the available genomic sequence, detection of ORFs, and then
detection of signal peptides and transmembrane domains in the resulting
protein. More than 4,000 new genes were discovered this way. The validity of
the predicted genes has been confirmed experimentally for more than 90% of
the cases in Compugen's molecular biology lab, by PCR and sequencing, and in
many cases through protein expression. Primers were designed to "fish
out" the predicted transcripts, and PCR was run on cDNA from tissue
samples, followed by sequencing the resulting products Technion researchers develop
'glue' to support broken bones
Researchers at the
Technion - Israel Institute of Technology in Haifa – have developed "a
bone glue," a material that combines biological and synthetic components
that when mixed together, supports broken bones and allows them to grow new
bone tissue. After the broken bone has fused, the material is broken down in
the body. The material was developed in the Technion's Department of
Biomedical Engineering by Dr. Dror Seliktar and Liora Almani-Levy, a master's
degree student. According to Seliktar, it is common practice in orthopedic
medicine today to use various types of screws and steel pins to fix broken
bones in place and thereby help them to fuse; sometimes, he says, a material
known as "bone cement" is also used. "These
materials," Seliktar continues, "only give the bone the
structural-mechanical support it needs, and do not facilitate the regeneration of bone
tissue at the damaged site. Seliktar says that although biological materials
used today to rehabilitate damaged tissues
encourage tissue regeneration, they do not provide the regenerated tissue
with the physical strength. "The material we have developed," he
says, "does both." The new material, known for now as Gelrin, is
comprised of Fibrin and the polyethylene, Glycol.
Fibrin is a protein produced in blood plasma and serves as a central element
in the blood clotting process; the Glycol is a transparent plastic material. The Technion
researchers have found a way to bind the molecules of the two substances to
form a new material that has biological characteristics and can also be
adjusted to different strengths. The cells of the body identify the new
material as "a friendly substance," on which regenerated tissue
that supplements boneless areas can be grown. "In fact, the bone tissue
grows within the Gelrin; and as soon as the tissue fills the space, the
material breaks down and washes out in the urine," Seliktar explains,
adding that one of its advantages is that it can be injected into the damaged
area without need for surgery. Till now, tests with Gelrin have been
conducted on cells grown under laboratory conditions, with trials on rats to
begin within the coming days. Seliktar says both substances that make up the
Gelrin are used in medicine today and both are approved by the U.S. Food and
Drug Administration. "I believe the FDA will not have a special problem
with the fact that we have combined the two substances; hence, if the
material proves itself as effective, it will receive the FDA's
approval." The Technion has registered a patent on the development of
Gelrin, and Seliktar says that the institute is currently in talks with an
entrepreneur who has heard of the material and is interested in establishing
a start-up that will develop applications for it. In the United States alone,
some one million bone-replacement operations are conducted each year. http://www.haaretz.com/hasen/spages/385113.html By Yuval Dror, Haaretz
Correspondent Who's afraid of biotech?
Virtually everything
good that you've heard about biotechnology is true. It's making inroads
against killers such as cancer, heart disease, and stroke. It's stopping
other diseases for which until recently the best treatment was an aspirin.
Biotech crops will provide malnourished peoples with enough calories to turn
them into American-sized butterballs. But to many, biotech has a dark side.
They fear cloning humans to rip out their organs as replacements, turning our
offspring into ubermenschen, and distorting the whole concept of what it is
to be human. Happily, though, almost all of the bad about biotech would be
senseless, scientifically impossible, or far more readily done through
alternative technologies such as bionics. Or the developments actually don't
seem very unusual - much less scary - when considered in a broader context.
Consider the idea of growing human clones for replacement organs, with some
terrifying scenarios depicting headless bodies connected to life support
until the organ is required. But already biotechnology is fabricating organs
such as bladders and even relatively complex ones such as penises. The
immorality of murdering a human aside, why grow and sustain a whole person
for an organ you may never need when you can buy an individual organ
"off the rack" or have it specially made for you? Not all controversial
applications of biotech lie in the realm of fantasy, though. A real scenario
is the use of stem cells from human embryos, which many see as violating the
sanctity of human life. Even those who don't feel that way must recognize
that others do, and thus it leaves biotech with a black eye. But it's often
the case with biotechnology that new advances eliminate older problems. In
the last two years, three different US labs have found evidence that three
different types of non-embryonic stem cells - those taken from adults,
umbilical cords, or placentas - appear to be able to mature into any cell in
the body. Even if all three labs fail, so many different non-embryonic stem
cells have been found that can be converted into so many different types of
mature tissue that there should be no need for "one-size-fits-all"
stem cells. Researchers whose reputations are built on embryonic research and
require funding to keep their labs going often insist that non-embryonics are overrated or even
worthless. But non-embryonics have actually been used therapeutically since
the 1980s for limited purposes such as treating leukemia, even as embryonics
are only now moving into animal testing. WHAT ABOUT what is
called "germ-line" gene-alteration to "improve" the human
race as a whole or at least your line of descendants? Research will
eventually allow changing such genetic attributes as intelligence or
appearance. Johns Hopkins University political science professor Francis
Fukuyama devotes many pages to this in his book Our Posthuman Future:
Consequences of the Biotechnology Revolution. But most of Fukuyama's fears
have already come to pass through other technologies, albeit ones that cannot
be passed down genetically. Improving your child's looks is as easy as
something called "cosmetic surgery." Improving his or her IQ is as
simple as flicking off the TV and putting away the video games. The argument
that the rich will have better access to germ-line therapy also falls flat;
the rich have better access to everything. For example, wealth can promote
higher intelligence even as the child is in the womb by providing better
nourishment. After that it can be used to pay for the best pre-schools,
schools, and tutors. In any event, the most efficient way to create
super-humans will never be with biotech. The technology is inherently limited
by the genes that God and nature have provided us. You can turn them on or
off or move them from one organism to another, but a gene can never do what
it wasn't intended to. But bionics, the use of implanted computer chips and
electronic or electro-mechanical devices, has no such limits. Bionics has
already brought us "neuroprostheses" such as the cochlear implant
that popular American talk show host Rush Limbaugh received. First approved
back in 1984, these bypass the normal hearing mechanism to provide artificial
hearing to deaf people. Next stop: superhuman hearing. Implanted retinal
chips are providing limited vision to those who were completely blind but
will surely eventually bring superhuman vision. Then there are implantable
computer brain chips. These are already used to control the tremors of
Parkinson's and the seizures of epilepsy. But again the therapeutic will lead
to the super. Already monkeys have been given the ability to move a robot arm
and a computer cursor with their thoughts alone. The same signals that enable
a small arm to pick up food could just as easily move a wrecking crane. Chips
being tested in animals will soon increase people's range of senses beyond
hearing and seeing. Through wireless connections such as the
already-ubiquitous WiFi (80211.x ), they will allow invisible communication
with others directly to and from the brain and thus bypass the eyes, ears,
and mouth. They will enable consistent and constant access to information where
and when it is needed, with no annoying pop-up ads. Fukuyama also frets over
the likelihood that biotech will allow us to live to be 150 and beyond; but,
illustrating the problem of a social scientist suddenly turned life science
commentator, he speculates we will live those last 50 years bedpan-bound and
drowning in drool. Yet of the incredible array of such therapies under
development that would slow, stop, or even reverse aspects of aging, all
would extend not just life itself but also the period before decrepitude.
Moreover, probably before any of these therapies is available, biotech will
have cured some of the cruelest diseases of aging, such as Alzheimer's. Dr. Leon Kass, chairman
of the President's Council on Bioethics, urges us to "resist the Siren
song of the conquest" of death. But he sets up a straw man. Even
reversing aging cannot confer eternal life. There are organisms that appear
genetically programmed to live indefinitely, such as certain trees and
turtles. But something catches up to them eventually, be it a chainsaw or
somebody hungry for turtle soup. Likewise, biotech cannot confer immortality.
But Kass is on firmer ground when he questions lifespan extension, if only
because he does so with non-scientific arguments. The best of them might be summarized as Why give
people more years when they seem so intent on wasting the ones they have,
plopped in front of the tube for hours on end watching other people's
"reality" because they don't have one of their own? The only answer
is that just as a knife that can be used for slicing or for stabbing,
biotechnology is a tool; nothing more. What can be accomplished with that tool is literally
miraculous. What will be is up to us. The writer, a senior fellow at the
Hudson Institute in Washington, DC, is author of BioEvolution:
How Biotechnology Is Changing Our World. His website is www.fumento.com. Jerusalem Post, Jan.
15, 2004 By MICHAEL FUMENTO Announcements EOI's for
the Sixth Framework Tel
Aviv university has published the EOI's for the Sixth Framework on the web,
and invites interested partners from the Extra
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