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Understanding Drosophila Development at the
Molecular Level
Gene Myers
EECS, UCal, Berkeley
On Systems Biology

The goal is to understand cells and organisms as molecular
systems. An objective that can be reached in the next 10-25
years is the elucidation of the topology of the “circuit”
diagram of a species’ cells.

Rationale drug design will become a reality.

We will be able to predictable modify systems at the cellular
level.
My Drosophila Plan
 Accurately reconstruct 6-12 Drosophila genomes with a shotgun approach as
cost-efficiently as possible.
 Compare the Drosophila genomes to:
 Understand evolution of whole genomes
 Better predict the genes and regulatory signals within each
Evolution as Genomic Rearrangements
Based on sequence
anchor blocks
Courtesy Lisa Stubbs
Oak Ridge National Laboratory
Comparative Gene Finding
Find genes by requiring all HMM models (ab initio),
trained for each genome on cDNA-discovered
(homology) genes, to be highly probable subject to
the constraint that the encoded proteins are
consistent with the evolutionary relatedness of the
species (comparative).
40M
30M
20M
10M
sechellia
mauritiana
simulans
melanogaster
orena
teissieri
yakuba
mimetica
pseudoobscura
0M
Given a ladder of 5-10 Drosophila genomes we should be able to
accurately discern most protein encoding genes, many RNA
genes, and a host of regulatory signals
My Drosophila Plan
 Accurately reconstruct 6-12 Drosophila genomes with a shotgun approach as
cost-efficiently as possible.
 Compare the Drosophila genomes to:
 Understand evolution of whole genomes
 Better predict the genes and regulatory signals within each
 Empirically validate all genes and their alternate splice forms.
 Measure (e.g. ChIP-chip) or infer from spatio-temporal expression, the cisregulatory control of all genes and their transcription factor binding sites.
 Build a spatio-temporal model of Drosophila embryonic development and
associated regulatory-control “circuit”.
 Dissect cellular complexes (pull-downs + MS) and signal cascades (in vitro
MS/MS)
Expression of Gene CG14897
Stage 4: Pole Plasm
Stage 1: Maternal
Affy expr. profile: 1st 12 hours
Stage 8: Neuroderm Anlage
Stage 14: Embryonic
Central Nervous System
Stage 11:
Protocerebrum
Primordium
Sea Urchin Endo-Meso TF “Circuit” (Davidson Lab, Caltech)
Some possibilities

Intuitive systems for scientific analysis

Modeling of molecular processes in multi-cellular systems.

New paradigms for architecting software

Nano-exploration of the cell

Fully robotic molecular biology lab