We are broadly interested in the structure, function and evolution of genomes. More specifically, we study the topics of telomere biology, cellular immortality, repetitive DNA, genome stability, genome silencing and small RNAs using the nematode Caenorhabditis elegans as a model system.
C. elegans has a relatively compact ~100 MB genome whose sequence is completely assembled. We are interested in repetitive DNA, including the simple repeat sequence (TTAGGC)n present at C. elegans telomeres, which is closely related to the mammalian telomere repeat (TTAGGG)n. We are also interested in regulation and function of transposons, which make up 15% of the C. elegans genome and almost half of mammalian genomes. Transposons are parasites that occasionally enter a naive genome via horizontal gene transfer and then replicate, creating several copies of themselves before they are silenced by the host. Retrotransposons are a class of transposons that replicate via an RNA intermediate that is copied into DNA by a reverse transcriptase. The simple repeats that are present at most eukaryotic chromosome ends are maintained by addition of de novo telomere repeats via a domesticated reverse transcriptase called telomerase, using a telomere template sequence that is present in the non-coding RNA subunit of telomerase. Telomerase is active in human germ cells but is silenced in human somatic cells, which creates a ‘telomere clock’ that represses tumor formation by limiting cell proliferation.
Cellular immortality, telomere biology, small RNAs, genome silencing, epigenetic inheritance, stress, longevity