Build­ing cus­tom-made DNA codes

China Daily (Hong Kong) - - YOUTH -

NEW YORK — At Jef Boeke’s lab, you can whiff an odor that seems out of place, as if they were bak­ing bread here.

But he and his col­leagues are cook­ing up some­thing else al­to­gether: Yeast that works with chunks of man-made DNA.

Sci­en­tists have long been able to make spe­cific changes in the DNA code. Now, they’re tak­ing the more rad­i­cal step of start­ing over, and build­ing re­designed life forms from scratch.

Boeke, a re­searcher at New York Univer­sity, di­rects an in­ter­na­tional team of 11 labs on four con­ti­nents work­ing to “re­write” the yeast genome, fol­low­ing a de­tailed plan they pub­lished in March.

Their work is part of a bold and con­tro­ver­sial pur­suit aimed at cre­at­ing cus­tom­made DNA codes to be in­serted into living cells to change how they func­tion, or even pro­vide a treat­ment for dis­eases. It could also some­day help give sci­en­tists the pro­found and un­set­tling abil­ity to cre­ate en­tirely new or­gan­isms.

The genome is the en­tire ge­netic code of a living thing. Learn­ing how to make one from scratch, Boeke says, means “you re­ally can con­struct some­thing that’s com­pletely new”.

The research may re­veal ba­sic, hid­den rules that gov­ern the struc­ture and func­tion­ing of genomes. But it also opens the door to life with new and use­ful char­ac­ter­is­tics, like mi­crobes or mam­mal cells that are bet­ter than cur­rent

The no­tion that we could ac­tu­ally write a hu­man genome is si­mul­ta­ne­ously thrilling to some and not so thrilling to oth­ers.” Jef Boeke, a re­searcher at New York Univer­sity, who di­rects sci­en­tists work­ing on the yeast genome

ones at pump­ing out med­i­ca­tions in phar­ma­ceu­ti­cal fac­to­ries, or new vac­cines. The right mod­i­fi­ca­tions might make yeast ef­fi­ciently pro­duce new bio­fu­els, Boeke says.

Some sci­en­tists look fur­ther into the fu­ture and see things like trees that pu­rify water sup­plies and plants that de­tect ex­plo­sives at air­ports and shop­ping malls.

Also on the hori­zon is re­design­ing hu­man DNA. That’s not to make ge­net­i­cally al­tered peo­ple, sci­en­tists stress. In­stead, the syn­thetic DNA would be put into cells, to make them bet­ter at pump­ing out phar­ma­ceu­ti­cal pro­teins, for ex­am­ple, or per­haps to en­gi­neer stem cells as a safer source of lab-grown tis­sue and or­gans for trans­plant­ing into pa­tients.

Some have found the idea of re­mak­ing hu­man DNA dis­con­cert­ing, and sci­en­tists plan to get guid­ance from ethi­cists and the pub­lic be­fore they try it.

Still, re­design­ing DNA is alarm­ing to some. Lau­rie Zoloth of North­west­ern Univer­sity, a bioethi­cist who’s been fol­low­ing the ef­fort, is con­cerned about mak­ing or­gan­isms with “prop­er­ties we can­not fully know”. And the work would dis­turb peo­ple who be­lieve cre­at­ing life from scratch would give hu­mans un­war­ranted power, she says.

Rewrit­ten DNA has al­ready been put to work in viruses and bac­te­ria. Aus­tralian sci­en­tists re­cently an­nounced that they’d built the genome of the Zika virus in a lab, for ex­am­ple, to bet­ter un­der­stand it and get clues for new treat­ments.

The cut­ting edge for re­design­ing a genome, though, is yeast. Its genome is big­ger and more com­plex than the vi­ral and bac­te­rial codes al­tered so far. But it’s well-un­der­stood and yeast will read­ily swap man-made DNA for its own.

Still, rewrit­ing the yeast genome is a huge job.

It’s like a chain with 12 mil­lion chem­i­cal links, known by the let­ters, A, C, G and T. That’s less than one-hun­dredth the size of the hu­man genome, which has 3.2 bil­lion links. But it’s still such a big job that Boeke’s lab and sci­en­tists in the United States, Aus­tralia, China, Sin­ga­pore and the United King­dom are split­ting up the work.

By the time the new yeast genome is com­pleted, re­searchers will have added, deleted or al­tered about a mil­lion DNA let­ters.

Boeke com­pares a genome to a book with many chap­ters, and re­searchers are com­ing out with a new edi­tion, with chap­ters that al­low the book to do some­thing it couldn’t do be­fore.

To re­design a par­tic­u­lar stretch of yeast DNA, sci­en­tists be­gin with its se­quence of code let­ters na­ture’s own recipe. They load that se­quence into a com­puter, then tell the com­puter to make spe­cific kinds of changes. For ex­am­ple, one change might let them re­ar­range the or­der of genes, which might re­veal strate­gies to make yeast grow bet­ter, says NYU re­searcher Les­lie Mitchell.

Once the changes are made, the new se­quence used as a blue­print. It is sent to a com­pany that builds chunks of DNA con­tain­ing the new se­quence. Then these short chunks are joined to­gether in the lab to build ever longer strands.

The project has so far re­ported build­ing about onethird of the yeast genome. Boeke hopes the rest of the con­struc­tion will be done by the end of the year. But he says it will take longer to test the new DNA and fix prob­lems, and to fi­nally com­bine the var­i­ous chunks into a com­plete syn­thetic genome.

“The no­tion that we could ac­tu­ally write a hu­man genome is si­mul­ta­ne­ously thrilling to some and not so thrilling to oth­ers,” Boeke says. “So we rec­og­nize this is go­ing to take a lot of dis­cus­sion.”

ZHU XUDONG / XIN­HUA

The summer va­ca­tion is typ­i­cally a time for chil­dren to pur­sue their in­ter­ests. This summer, the Yu­lan Ex­per­i­men­tal School in North China’s He­bei prov­ince has or­ga­nized a pro­gram to of­fer free lessons in dance, mu­sic, cal­lig­ra­phy and paint­ing, among other fields, and more than 200 chil­dren are tak­ing ad­van­tage of the classes. Tian Mengt­ing (left) teaches stu­dents to play mu­si­cal in­stru­ments in Dongliushangu vil­lage, Linxi county, He­bei.

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