completed a post-doc in Basal Switzerland, Paul joined the Biology Department at Princeton University as an Assistant Professor in the fall of 1978. Accomplishments as a faculty member at Princeton cover a wide range of topics. In the area of chromatin, his lab, together with the lab of Abe Worcel, was one of the first to show that nucleosomes are not randomly distributed along the DNA. Instead, they occupy specific positions with respect to the underlying DNA sequence in Pol I, Pol II and Pol III transcription units and their flanking spacer DNAs. His laboratory was amongst the first to discover chromatin insulator or boundaries, to develop in vivo assays to test for insulator or boundary activity and to identify proteins/factors that confer insulator/boundary activity. Other chromatin work includes studies on Polycomb dependent silencing, trithorax group genes and transvection. In the field of sex determination his lab together with the lab of Tom Cline analyzed the role of the master-regulatory gene Sex-lethal in choosing and remembering the female or male identity. Pathway choice depends upon a special Sxl establishment promoter that is activated by the X chromosome counting system in female but not male embryos. Pathway memory depends upon sex-specific alternative splicing in which the protein product of the Sxl gene autoregulates its own expression. Recent studies on pathway maintenance have shown that splicing becomes uncoupled from transcription when Sxl pre-mRNAs are spliced in the regulated female pattern. In contrast, when the pre-mRNAs are spliced in the default, male pattern, splicing is tightly coupled to transcription. Moreover this seems to be a general feature of regulated versus default splicing as it also occurs in mammals. In the field of translational regulation, his lab discovered one of the first localized mRNAs, the product of the orb gene. orb is a member of the CPEB family of translational regulators, and was the first CPEB gene to be molecularly isolated and characterized. Like Sxl, an autoregulatory activity is critical to its function during oogenesis. Studies on germline development showed that nanos and polar granule component function to impose transcriptional quiescence on newly formed primordial germ cells (PGCs) and that this is critical in the specification of PGC identity. These studies also showed that the hedgehog morphogen functions as an attractant to guide the migration of the PGCs to the somatic components of the embryonic gonad.

 Genetic analysis of tRNA processing in E.coli-- identification of RNase P. Cloning of some of the first Drosophila Pol II and Pol III genes. Discovery that nucleosomes occupy unique positions with respect to the underlying sequence in 5s rDNA chromatin and histone repeat unit chromatin. Analysis of somatic sex-determination in Drosophila: Elucidation of the mechanisms for pathway initiation and pathway maintenance. Discovery of the Dorsal gradient in early Drosophila embryos. Identification and molecular/genetic characterization of chromatin domain insulators/boundaries. Analysis of the mechanisms of alternative splicing. Functioning of CPEB family proteins, Orb and Orb2, in oogenesis, spermatogenesis and asymmetric cell division. Demonstration that Hedgehog functions as a chemoattractant in germ cell migration and identification of novel hedgehog signaling pathway genes. Analysis of primordial germ cell specification- a) characterization of maternally derived factors required for the establishment of transcriptional quiescence and b) identification of a somatic signaling pathway required for germ cell specification and sex determination.