“… from so simple a beginning, endless forms most beautiful and most wonderful have been, and are being, evolved.” – Charles Darwin, On The Origin of Species
Genomes are incredibly effective at encoding biological information: all biology starts from a chain of nucleic acids (DNA/RNA) and culminates in the natural world around us. Some of that biology is strange and interesting in ways that might be leveraged for human advancement: understanding this biology starts at the sequence level.
Mutations in an organism’s genome fundamentally change how its biology is constructed. Most changes are negative in nature and are usually mitigated by genome repair mechanisms: these are highly effective in healthy, young individuals, but deteriorate significantly in aging. Unrepaired mutations destabilize the genome, and accumulated mutations tend to yield general cellular dysfunction and increase cancer risk over time.
Over the course of my PhD, I’ve developed end-to-end methods for studying these mutations in human DNA. I’ve focused on creating methods to capture de novo mutations, which occur over the course of gamete (egg and sperm) formation and can be passed down from parent to child. While rare, these mutations are the basis of human evolution over generations.
I specialize in using highly accurate long-read sequencing to characterize difficult-to-resolve mutations like structural variants (SV), defined as large (50 bp - chromosome scale) aberrations in the genome. In the wet lab, I’ve developed DNA extraction and sequencing methods to optimize SV capture. In the dry lab, I’ve created tools and pipelines for identifying ultra low frequency SVs directly from single reads.