Transcript Gene Myers
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