Computational Biology and Bioinformatics Discussion Group
Thursday, March 23, 2006
Presented by the Computational Bio & Bioinformatics Discussion Group
Organizer: Burkhard Rost, Columbia University
The Computational Biology and Bioinformatics Discussion group brings together diverse institutions and communities to share new and relevant information at the frontiers the inter-related fields of bioinformatics and computational biology. Recent topics have included "Benchmarking and Improving the Accuracy of Comparative Modeling of Protein Structures," "Integrated Statistical Modeling of Gene Expression Data" and "Estimating SNP Haplotype Frequencies from DNA Pools."
5:00 pm - 7:00 pm: Presentations
George Yancopoulos, Regeneron Pharmaceuticals, "VelociGene & VelociMouse: High-Throughput Mouse Genetics Approaches Providing Enormous Informational Challenges and Opportunities for Computational Biologists."
Joel Bader, Johns Hopkins University, "Reverse and Forward Engineering of Biological Systems."
Isaiah Arkin, The Hebrew University, D.E. Shaw Research, "Interesting Membrane Proteins from SARS and Influenza."
"VelociGene & VelociMouse: High-Throughput Mouse Genetics Approaches Providing Enormous Informational Challenges and Opportunities for Computational Biologists"
Perhaps the most powerful approach for exploring gene function involves the generation of mice with mutations in specific genes; resulting phenotypes in these mice often provide enormous insight into the biologic role of the mutated genes. Unfortunately, mouse genetics has heretofore involved laborious and time-consuming steps to generate each individual mouse mutant. Recognizing the power of mouse genetics, but also realizing its limitations, we developed two integrated technologies termed VelociGene and VelociMouse that together allow for an unprecedented rate of generation of specifically designed mouse mutants — easily industrializable and scaleable to thousands per year. These approaches involve rapid manipulation of very large pieces of DNA — hundreds of kilobases in size — allowing the entire genome to be spanned by about 25,000 separate pieces of DNA. VelociGene has enormous flexibility, allowing the production of custom mutations with nucleotide precision, "knock-outs" and deletions of very large size, reporter "knock-ins", transgenic over-expression, as well as conditional and complex alleles. Genetically modified mice produced via VelociGene and VelociMouse can be phenotyped using a variety of high-throughput approaches, ranging from high-throughput/high-resolution reporter gene analyses to localize the target gene with cellular resolution, to four-dimensional transcriptional fingerprinting via microarray in the tissues of a genetically modified mouse. These approaches can generate very dense gene-linked functional information that present enormous informational challenges and opportunities for computational biologists. Exploitation of VelociGene and VelociMouse technologies for the purpose of identifying new targets for drug discovery will also be discussed.
"Interesting Membrane Proteins from SARS and Influenza"
In my talk I will describe computational and experimental studies of two small membrane proteins from SARS corona virus and Influenza. In SARS coronavirus I will describe the unusual topology of the E protein and the influence of this topology on the protein's function. In Influenza I will talk about the M2 proton channel. I will describe our studies unraveling the gating mechanism of the protein as well as how this protein assists the virus to develop resistance against anti-viral treatments.
"Reverse and Forward Engineering of Biological Systems"
This talk will occur in in two parts:
(1) Ab initio reverse engineering of transcriptional regulation.
Gene regulation depends on transcription factor proteins that recognize