The Beier Lab's research projects include:
Forward Genetic Analysis for Disease Gene Discovery in Mouse Models
A major focus of the lab has been screening ENU-mutagenized mice for defects in organ development. We have pursued a number of different approaches, with specific targets that include craniofacial, cardiac and neurodevelopmental defects.
These mutants have provided important insight in human disease. For example, we characterized mutations of the gene Fog2as associated with human congenital diaphragmatic hernia; this was the first causal gene discovered and is the most common mutation characterized in this severe developmental defect.
Our most recent effort is an analysis of modifying genes that affect skeletal growth and patterning. Of note is that the positional cloning component is often simply the beginning of the story - the experimental task of understanding mechanistic consequences of developmental defects is challenging and rewarding.
Cilial Genes and Polycystic Kidney Disease
Several of our positional cloning efforts have uncovered genes that play in cilial physiology. For example, Nek8, which is required for normal left-right patterning and which is associated with a cystic kidney disorder, is the only kinase reported to localize to the cilial axoneme. Ttc21bis a component of a complex of proteins that mediate retrograde intraflagellar transport, and our analysis of a conditional mutant have implicated hedgehog signaling in kidney cystogenesis. Other cilial genes we have identified have been implicated in craniofacial development and hydrocephalus.
Genomic and Imaging Technology and Developmental Genetics
Sydney Brenner has stated that "progress of science depends on new techniques, new discoveries and new ideas, probably in that order." We have endeavored to apply new technologies to fundamental questions of biology. These include next-generation sequencing techniques, novel methods of genome modification in both mouse and zebrafish, computational analysis and highly sensitive methods for imaging developmental processes.