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A major biology platform for DanioLabs
involves technology based around the use of zebrafish: The
US National Institute of Health (NIH) has ranked
zebrafish as the 3rd most
important species for research after man and rodents.
The Welcome Trust Sanger
Institute is sequencing the
zebrafish genome. Some of the key benefits of zebrafish
include:
1. Short reproductive cycle.
2. Large number of offspring per mating.
3. Embryos are transparent allowing internal organs and
neurons to be visualised.
4. Strong correlation between human genetics, anatomy
and disease.
5. Rapid layout of body plan, allowing study of disease
at early stages of embryonic development.
6. Ethically preferred in the drive to reduce, refine
and replace.
7. Cost effective.
Within 24 hours of development all of
the major organs have been laid out, and by 72 hours
the fish can see.
However, the main reason zebrafish
have become one of the premier organisms for biological
study over the
last few years is because they are vertebrates
and model human biology closely. It was this unique
combination
of scalability, genetic tractability and modeling capability
that led developmental biologists to choose this organism
to study vertebrate development, culminating in a series
of seminal publications in 1996.

Zebrafish are tiny. A fixed specimen
is here shown next
to a 1p piece
Although these initial screens were
intended to pick out developmental mutants, disease-relevant
mutants were
also found. Two of the earliest mutant genes that were
mapped proved to be homologous to the human genes predicted
from the phenotype: hepatoerythropoietic porphyria -
uroporphyrinogen decarboxylase; sideroblastic anaemia
- aminolevulinate synthase. An impressive array
of cardiovascular mutants were also identified, including
mutants with bradycardia, atrio-ventricular block and
atrial fibrillation. Detailed analysis in a variety of
organ
systems has
now shown striking similarities with humans. For example,
the zebrafish retina is morphologically very similar
to the human retina.
The human disease modeling capabilities
of zebrafish have been highlighted in several review
articles including: Pichler
et al; Rubinstein; Goldsmith
et al; Shin
et al; Penberthy
et al.
The DanioLabs approach
DanioLabs has developed an intellectual
property portfolio and a proprietary knowledge
base around the use of zebrafish
in the drug discovery
process. We have established how best to integrate them
into our drug discovery programmes such that they are
now a key part of this
process for DanioLabs.
This
is
evidenced
by
the richness
of our pipeline.
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