Mission statement:
Completion of the Saccharomyces genome deletion project, which created more than 5900 Òmolecular-barcodedÓ yeast knockout mutants (YKO mutants) has facilitated large scale analyses of mutant phenotypes, including synthetic lethality screens. We have developed a methodology for this called Synthetic Lethality Analysis by Microarray (SLAM), variants of which can be applied in many different ways to dissect the networks of genetic interactions that define living cells. Global synthetic lethality analysis promises to identify cellular pathways that ÒbufferÓ each other biologically, informing our understanding of genetic predisposition to diseases and cancer. The combination of global synthetic lethality data, together with global protein-protein interaction analyses, mRNA expression profiling and functional profiling will in principle enable construction of a cellular Òwiring diagramÓ, helping frame a deeper understanding of human biology and disease.
Overall our group is addressing several major goals:
* Generate a genome-wide genetic interaction map based on null allele-null allele interactions. This network will sharply define branched and parallel pathways.
* Build a database to house the above information, serve interaction lists to the community of yeast researchers, and provide more extensive network-level data to computational biologists.
* Connect each genetic interaction datum to a probabilistic statement as to likelihood of being a biologically confirmable synthetic lethal or synthetic fitness interaction.
* Generate robust computational tools for the building, visualization and interpretation of genetic networks.
* Build a database to accept phenotypic data on large-scale screens done on the YKO collection and other systematic collections of mutants.
* Provide practical support for yeast biologists and others interested in using the Hopkins TAG Array platform for SLAM, d-SLAM and other applications.
* Generate Ts mutant and hypomorphic allele collections in all essential yeast genes.
* Develop techniques for the analysis of Ts and hypomorphic alleles using SLAM, and appropriate databases and computational tools to interpret these.
* Develop novel yeast strain collections and technologies and disseminate them to the community.