Research in our laboratory has sprung, in one way or another, from an interest in the molecular mechanism of transposition in eukaryotes. We like to exploit the diverse genetic approaches available in yeast as an experimental organism, as well as more biochemical approaches. Our work is focused on yeast and human retrotransposons, which represent the two major structural types of retrotransposons, those with and those without long terminal repeats (LTRs):
1.The molecular dissection of yeast retrotransposon Ty1, its assembly, reverse transcription and integration reactions as well as its interactions with host factors.
2.Determination of the molecular mechanisms involved in retrotransposition of the human L1 element.
The genomic compartment inhabited by retrotransposons is often "heterochromatin", which in yeast is characterized by the "silent" state of inserted reporter genes. We are studying two major aspects of gene silencing, the Sir2 family of histone deacetylases which are modifiers of histones and other protein that play a critical role in silencing as well as the histones themselves, which can be manipulated by elaborate yeast genetic systems. Our genetic work is complemented by the structural biology performed by our collaborators in the laboratory of Cynthia Wolberger.
We also seek to push the envelope of yeast genetic technology. We extensively employ powerful TAG array technology that reports on gene function rather than expression level. We are building a Genetic Interaction Map of Yeast by systematic synthetic lethality mapping and related techniques. This work is an important collaboration with the laboratories of Forrest Spencer (IGM), Rafael Irizarry (Biostatistics) and Joel Bader (Biomedical Engineering).
