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Gene drive: what is possible at the population level with currently-available molecular components?
Published on July 31, 2018 52 min
Other Talks in the Series: Gene-Drives and Active Genetics
Gene drive behavior when pest populations have age, mating and spatial structure
- Prof. Fred Gould,
- Prof. Alun Lloyd
Engineering reciprocal chromosomal translocations to control the fate of populations
- Dr. Omar Akbari
- University of California, San Diego, USA
CRISPR-based suppression drives for vector control
- Prof. Andrea Crisanti
- Imperial College London, UK
I'm John Marshall, an Assistant Professor in Residence at the University of California, Berkeley in the School of Public Health. And I'm going to be giving a talk on Gene Drives and Active Genetics. Specifically on gene drive, what is possible at the population level with currently available molecular components?
So, the work that I do focuses on mathematical modeling of gene drive systems. So, I'm going to be talking about them from that perspective. And to begin with, we will talk about Medea and underdominant drive systems. So, Medea itself, is toxin-antidote-based underdominant systems including Semele and UDMEL, and also reciprocal chromosomal translocations. So then, we'll have to talk about the mathematical modeling frameworks that can be used to study the spread of these gene drive systems through spatially-structured mosquito populations. One of which is MGDrivE, which stands for Mosquito Gene Drive Explorer and another is MASH or Modular Analysis and Simulation for human Health. And then, we will discuss homing-based gene drive systems and the potentials developed confineable homing-based systems that may be able to be limited and extend to their spread spatially, and also the potential for invasive homing-based gene drive systems following field trials when it may be desired, they spread on a wider scale.
Beginning with Medea, Medea was the first synthetic gene drive system to be engineered. It was engineered in the lab of Bruce Hay at Caltech, which I was a postdoc in, and it's based on the function of the maternal toxin which is linked to a zygotic antidote. So, if we look at the crosses, then heterozygous or homozygous mothers produce a toxin which will affect all of their offspring. And then the offspring, if they inherit the zygotic antidote as part of the Medea element, will be protected against the action of this toxin, and the results in the rightmost cross is that only wild-type offspring of heterozygous females will be rendered unviable by this construct. But the result of that is that it actually places a selective advantage on having the Medea construct and a disadvantage on not having it, and therefore, over time, the Medea elements spreads into the population and is capable of spreading to the population from very low initial frequencies.