In The Field

Transplant is Neat, But for Assembly, Nature Still Has Us Beat

Questions about the infamous Venter patent didn’t come up at Hamilton Smith’s talk this morning. Smith, a Nobel Laureate and well known as J.C. Venter’s right hand man talked about an ongoing project at the Venter Institute to define a minimal set of genes needed for life. The minimalist Mycoplasma genitalium has been the focus of study for its already sparse genome (it’s about 580 kb long and contains just under 500 genes).

Smith talked about three ongoing projects on M genitalium: 1) reducing the genome to its lowest number of necessary genes, 2) synthesizing and assembling a new M. genitalium genome from scratch for the purpose of 3) transplanting it into a recipient cell and creating essentially a new organism which Smith called M. laboratorium.

So, number 2 has proved quite tricky and I’ll get back to that, but the group at the Venter Institute has made quite a leap in the transplant area. They took two, somewhat easier to grow species of Mycoplasma – Mycoplasma capricolum and Mycoplasma mycocides – and they plugged the genome from the latter into the cell of the former. Rather than remove the M. capricolum genome from the hybrid cell, they hoped that the cell would essentially divide leaving one daughter cell with a completely new genome. Based on the evidence Smith showed it seemed to work quite well, and not that inefficiently. The idea that another organism’s genome could essentially boot up the cytoplasm of cell and establish itself, is nothing short of amazing.

The question remains whether they can do this with a laboratory synthesized genome copy of M. genitalium. They built the genome in 101 pieces painstakingly checking for errors through sequencing, and they’ve been working hard trying to put those pieces together since at least the last time I’d heard Smith talk, which was in 2005.

One had to note the irony in the placement of the second talk, then, in which Miroslav Radman of Necker Institute, France, discussed the epic genomic reconstitution abilities of Deinococcus radiodurans. After blasting this bacterium with something on the order of 14kiloGrays of radiation, Radman showed how the genome completely reconstitutes itself in a matter of about 4.5 hours. His work has been showing to some extent how this organism pulls this mighty feat off through synthesis dependent strand annealing thanks in part to a protein for recombination recA that has evolved to survive extreme dessication.

This kind of genome reassembly that happened naturally would be a pretty neat trick for Smith et al. as at least one questioner noted in the questions session following Radman’s presentation. If I recall correctly, the Venter team had been considering using the amazing qualities of radiodurans, but in Smith’s presentation, the process described was more along the lines of traditional molecular biology techniques. It would be neat if they could create the synthetic organism that they’ve claimed a patent for, but alas they haven’t yet.

Now, I’m going to learn more about the property rights issues synthetic biologists are facing.


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