Loss-of-function screens in mammalian cells with esiRNA RNA interference is becoming the method of choice for gene function analysis in cells and whole organisms. Our lab has developed innovative technology to perform large scale RNAi experiments in mammalian cells and in mice. We use enodibonuclease prepared siRNA (esiRNA) for the efficient and specific knock down in genome wide screens to identify and characterize genes relevant to cancer biology and differentiation.
Normal and malignant haematopoiesis Haematopoietic and endothelial cells arise from a common precursor, commonly referred to as the haemangioblast. The decision whether the cells differentiate into the blood- or vessel- lineage seems to correlate with the expression of certain “master switch genes”. One of these important genes for lineage specification is the runx1 gene. Runx1 seems to participate in the fate decision in favor of haematopoietic development. Its pivotal role during development makes runx1 also a good candidate to play an important role in adult stem cells. Interestingly, runx1 is also one of the most frequently mutated genes in human leukemias, supporting that runx1 plays an important role in the adult. We study the role of runx1 during development and in adult mice. A better understanding of this master switch regulator may help to understand, how cells that have a common origin take on a specific fate in the body to build an organ and may also help to understand the development of certain leukemias.
Advanced genome engineering The need for fluent and precise genomic manipulation strategies has been exacerbated by the increasing pace of published genome sequences. Beyond the reading of complete genomes, the precise manipulation of the encoded information is becoming more important in modern molecular biology. Site specific recombinases are prominent genetic engineering tools that allow the genetic manipulation of whole organisms. In order to expand the usefulness of these enzymes we are designing novel recombinases through directed molecular evolution and test them for their usefulness in biology and medicine.
Future prospects and goals
Improve esiRNA technology for functional genomic studies.
Perform RNAi screens in mouse ES cells to identify and characterize factors involved in self renewal and differentiation.
Perform phenotypic profiling of cancer cell lines and identify and characterize candidate genes with therapeutic potential.
Study the role of Runx1 in the developing and adult mouse.
Develop and apply tools that allow flexible and precise genomic manipulations.
