Currently the Maniatis Lab is pursuing three directions: Protocadherin gene expression and function, ALS disease mechanisms and Innate Immunity. A consistent theme in all three projects is the use of molecular and cellular approaches to understand both basic biological and disease mechanisms.
Protocadherin Genes: Several years ago we discovered a unique genomic organization of a cluster of genes encoding protocadherins, which are single pass trans-membrane proteins bearing immunoglobulin-like extracellular domains.
The genomic organization of mammalian protocadherin genes. The colored vertical bars indicate variable exons encoding the trans-membrane and extracellular domains, and the black bars correspond to exons encoding intracellular domains.
Studies of protocadherin gene expression mechanisms revealed that each variable region exon is transcribed from a promoter located upstream from each variable region exon. Transcripts generated from each promoter are spliced to the first downstream variable exon as shown below. Thus, individual isoforms are generated by promoter choice.