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| High
Throughput Screening |
| HTS involves biochemical-level
screening that uses robotics systems
to process large libraries of
potential drugs. Traditional drug
discovery would result in screening
a couple of hundred compounds
a month. A hundred-fold increase
in the number of assays that can
be performed is possible with
high throughput screening. |
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| Molecular
Modeling |
| This technique
is based on the relationship between
chemical structure and biological
response. Computer-generated models
of molecules allow scientists
to examine receptor binding sites
and propose biological activity. |
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| Bioinformatics |
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In addition to the more traditional
means (scientific literature/knowledge)
for determining biological targets,
computerised genomics research
techniques in conjunction with
appropriate laboratory methods
(e.g., DNA sequencing, cloning,
differential display, protein
expression, ...) are utilised
to uncover novel and unique
biological targets.
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Bioinformatics involves using
data from the genomic database to
evaluate gene sequences that may
point to new drug targets. A fully
computerised searching system is
employed to integrate information
retrieved from the PRI-derived gene
database with both licensed, private
and public databases. The overall
goal is to determine which genes
are expressed differently from normal
in disease states. Future directions
include the use of microchip technologies
to screen the increasing gene database
for abnormalities in disease and
potential targets for drug discovery
research.
While scientists on all teams
have access to genomics research
technologies and computerised data
gathering capabilities, the majority
of our bioinformatics activities
in the United States occur at Discovery’s
La Jolla, California facility. Scientists
at La Jolla have developed systems
internally and through collaborations
with outside genomics-research organizations
that are shared with JRF scientists.
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| Human
Receptor Culture |
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Human receptors are cultured
by separating the genetic material
that produces receptors from
the blood cells or other human
tissue. This "blueprint" is
inserted into bacteria, yeast
or cell lines where it can be
reproduced easily. This biotechnological
method permits the development
of drugs that are "made to measure"
from human receptors.
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As an important additional benefit,
it is possible to carry out tests
on the receptors in vitro without
using experimental animals.
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| Human
Genome Mapping |
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The increasing knowledge available
from the human genome mapping
project has had a profound influence
on pharmaceutical research.
A drug’s interaction with its
receptor is examined by introducing
small, well-defined mutations
in the isolated receptor gene.
Studying how drugs bind and
activate these
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altered receptors provides insight
into the role of the altered parts.
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| Positional
Gene Cloning |
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So far, the spectacular successes
in elucidating genes responsible
for genetic disorders using
the positional cloning strategy,
have nearly all involved relatively
rare disorders caused by mutations
in a single gene. Deciphering
the genetic basis of complex
genetic disorders such as schizophrenia,
major depression, psoriasis,
alcoholism and others, is a
far more daunting task.
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But complex disorders are now moving
to the centre stage of gene mapping
and gene identification. New mapping
techniques, based on disequilibrium
mapping in isolated populations, combined
with the development of high throughput
sequencing technologies and improved
methods for gene identification should
enable us to isolate these genes.
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