Lecture 2
Nanopore technology: from DNA sequencing to drug discovery
| Speaker | Distinguished visitor Prof Jens Gundlach, University of Washington, Seattle |
| Date/Time | Monday, 28 Oct, 2PM |
| Location | Lecture Theatre 32 |
| Moderator | A/Prof Wang Zhisong |
Abstract
My biophysics group was the first to realize nanopore sequencing of DNA. We started by engineering the biological protein nanopore MspA into a sensor capable of distinguishing individual nucleotides within single-stranded DNA. Then, we used an enzyme to draw the DNA through the pore. After successfully demonstrating this concept, we recorded kilobase-long reads and showed that our method could also detect epigenetically modified bases.
Once our sequencing process was adopted by industry, we leveraged our detailed understanding of nanoscale physics to further develop our nanopore technology into an ultra-precise single-molecule tool. This tool allows us to observe enzyme mechanics in real-time as these molecular machines move along DNA or RNA. Our “nanopore tweezers” achieve ten times better positional and temporal resolution than optical tweezers while simultaneously measuring the exact nucleotide sequence within the enzyme.
I will present previously unseen details in the motion of helicases, DNA and RNA polymerases, reverse transcriptases, and more. Our method not only establishes crucial kinetic enzyme models but also reveals many surprising properties of these enzymes. With our nanopore tweezers experiments, one can explore how drugs interfere with enzyme function and seek out entirely new drug candidates.
Biography
Jens Gundlach is Professor of Physics at the University of Washington in Seattle. He studied physics at the Johannes Gutenberg University in Mainz, Germany, and earned his Ph.D. in nuclear physics from the University of Washington. He then became interested in testing fundamental aspects of gravity. His group is well-known for the best tests of the equivalence principle, measurements of gravity at sub-millimetre separations and for inventing a more precise method to measure Newton’s constant, big G. His group also develops instrumentation to aid gravitational wave detection.
In 2004, Dr. Gundlach became interested in biophysics and soon emerged with breakthrough achievements. His group was first to demonstrate functional nanopore sequencing of DNA, which thereafter became a commercially available technology. Gundlach’s group then went on to develop an ultra-precise single-molecule tool to resolve the activity of enzymes with unprecedented precision.
With an attitude that nothing is impossible, Dr. Gundlach now runs two world-leading labs in diametrically opposite fields of physics.
In 2021 he was awarded the Breakthrough Prize in Fundamental Physics for his work on gravity.
