Jef D. Boeke
Professor of Biochemistry and Molecular Pharmacology
Professor of Biomedical Engineering
- Director of the Institute of Systems Genetics
- Member NAS, AAA&S
The laboratory of Professor Jef Boeke is well known for foundational work on mechanistic and genomic aspects of retro-transposition in both yeast and mammalian systems. In addition, the Boeke lab is heavily involved in the development of novel technologies in genetics, genomics and synthetic biology. His group uses yeast as a platform for exploring the construction of fully synthetic chromosomes for practical and theoretical studies. They have congregated an international consortium called SC2.0 to rewrite and synthesize the first eukaryotic organism, Saccharomyces cerevisiae. We project complete synthesis and “debugging” of the entire genome by the end of 2020.
NYU researchers at the Tandon School of Engineering and the Grossman School of Medicine are trying to understand an age-old question that bedeviled most of us at some point: Why do all the other animals have tails, but not me? The loss of the tail is one of the main anatomical evolutionary changes to have occurred along the lineage leading to humans and to the “anthropomorphous apes.” The loss of tails has long been thought to have played a key role in bipedalism in humans.
This curiosity-based question was addressed by using bioinformatics tools to look at differences between the genomes of humans (and the other apes, which all lack tails) and monkeys (which all have tails, like most other mammals).
Bo Xia, a PhD candidate studying this problem in the labs of Jef Boeke and Itai Yanai, looked at sequence alignments of all genes known to be involved in tail development and discovered a movable piece of DNA called a retrotransposon inserted in the TBXT gene, which is a developmental regulator crucial for tail development. The reason it had not been spotted before was due its placement in noncoding (intron) DNA, where most people would not look for mutations.
Examination of the gene, which carried other copies of the Alu retrotransposon, led to a model for how the Alu might disregulate splicing of TBXT RNA. The researchers engineered a mouse model to test this hypothesis and found that indeed, many mice with a suitably altered genome lacked a tail. They also found that the mice without tails also suffered from spinal cord malformations. It’s possible our ancestors who lost their tails also had this side effect, which may contribute to some health problems even today.
- Jef D. Boeke