Michael McManus, PhD
|School||UCSF School of Medicine|
|Address||513 Parnassus Ave|
San Francisco CA 94143
The McManus lab studies the basic biological processes relating to noncoding RNAs, using cultured cells and the mouse as a model. This includes the study of microRNAs, and the factors involved in small RNA production and activity. In a broad sense, the lab is interested in understanding how noncoding RNAs contribute to the specification of cell fate and function, for example, how deregulation of microRNAs may contribute to human disease.
Based on our studies of noncoding RNA biology, we have developed cutting-edge research tools and agents for the interrogation of gene function and the potential use in the intervention of human disease. We focus on small RNAs from both a tool and biology standpoint. Two current project areas are below:
Mouse knockouts of microRNAs. We have generated conditional mouse knockouts for Dicer, the catalytic engine of small RNA production in cells. We have used this mouse to explore the role of Dicer in many tissues and it is clear that it is key for normal cellular function in a broad array of tissues. However this is a low-resolution model for exploring small RNA biology, since many biologically important small RNAs are simultaneously depleted. For this reason, hundreds of conditional mouse small RNA knockout models are individually being made. Projects are available to phenotype these novel reagents.
RNAi libraries. One active effort in my lab relates to the derivation and use of whole-genome shRNA libraries that we have generated- these are powerful tools to interrogate gene function in cells. This is a unique resource since it contains large numbers of shRNAs that allow for the statistical de-convolution of hits using deep sequencing. Projects are available that center on genome-wide RNAi interrogation of gene function, particularly as it relates to the molecular dissection of the regulation of gene expression.
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