Bioscience Initiative

Bioscience Initiative
Leiden University

DNA sequencing technology and its applications to better understand the world around us

Van Leeuwenhoek Lecture on BioScience.

Thursday May 31 2018 at 16.00hrs.
Gorlaeus B├Ętacampus LUMY 04.28
Jim Mullikin (NIH, Rockville)

Jim Mullikin is the director of the NIH Intramural Sequencing Center (NISC) and an associate investigator in the National Human Genome Institute's Cancer Genetics and Comparative Genomics Branch. He develops and utilizes computer programs to analyze large data sets generated by systemic DNA sequencing projects. A computational genomicist, he collaborates extensively with biomedical researchers, analyzing data produced at NISC, by others or are available in public databases. His group is currently developing new methods to better interpret the huge volumes of data produced by next-generation DNA sequencers. Jim Mullikin holds a PhD in physics (image and signal processing) from Delft University of Technology.

The light bulb is often used as a symbol for someone with a bright idea. In the book "Fifty inventions that shaped the modern economy" , Tim Harford compared the ancient times when wood wires were the only means of human produced light to today's modern LED light bulb and calculated this to be a 500.000-fold cost reduction in light production over the last few thousand years. Contrasting this to our early ability to determine the nucleic acid sequence of the DNA molecule since the day of Fred Sanger and his dideoxy chain-termination invention for DNA sequencing in 1977 to today's sequencing-by-synthesis methds offers an incredible 400.000.000-fold cost reduction over a much shorter timeframe. Thus, there were a lot of bright ideas over the last 45 years making the tremendous advancement possible.

In this presentation I will cover some of the major advancements in DNA sequencing technologies and highlight two examples where DNA sequencing has acted like the microscope of van Leeuwenhoek's day, letting us see and understand things we could not see before. The first of these examples is the application of DNA sequencing of samples extracted from ancient hominid bones and how this shed light on equally ancient admixtures of Neandertals and humans 50.000 to 80.000 years ago.

DNA sequencing also led to the discovery of an entirely new hominid lineage by sequencing a sample which was thought to be a pinky of Neandertal or human, but is now called an entirely new archaic human lineage named after the Denisova cave in Siberia where the tiny bone was found. The second example is how DNA sequencing helped resolve the epidemiological history of an antibiotic resistant bacteria outbreak in a hospital setting. Not only were we able to track the bacteria from the few mutations acquired over the course of the outbreak from samples acquired across both patients and hospital systems (respirator, sink drains, etc.), but in a follow-up investigation we were able to follow the plasmids inferring antibiotic resistance across the bacterial isolates, identifying plasmid exchange from one bacterial isolate to another.



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