Jef D. Boeke, PhD

The Boeke lab has long been known for foundational work on mechanistic and genomic aspects of retrotransposition in both yeast and mammalian systems, and, after more than three decades, we continue to scrutinize our favorite genomic parasites. In addition, our lab is heavily involved in the development of novel technologies in genetics, genomics and synthetic biology.  Our group uses yeast as a platform for exploring the construction of fully synthetic chromosomes for practical and theoretical studies. We led an international consortium called Yeast2.0 to rewrite and synthesize the first genome of a eukaryotic organism, Saccharomyces cerevisiae. We project complete synthesis and “debugging” of the entire genome by the end of 2025.

In 2018, we launched the ambitious “Dark Matter Project” to begin parsing functions of non-coding DNA. Our initiative deploys innovative tech to introduce directed and substantial modifications to select mammalian gene loci. The process begins with the assembly of synthetic genomic constructs and even libraries of 100 kb and up engineered to contain systematic variations in yeast. The assemblies are then inserted at precise genomic locations in mammalian cells using precision delivery approaches and individual variants, or combination of variants, are surveyed for phenotypic effects. We are also using the approach to engineer genomes to produce extensively humanized mice and other animals, as well as introducing a broad range of genes, pathways and gene networks with the combined aims of modeling and mitigating disease states as well as new phenotypes in animals. Last but not least, we explore epigenetics and chromatin structure, as we are interested in deciphering the complexity of human chromatin organization by rewriting the system in budding yeast using a progressive bottom-up approach.