Proceedings of the National Academy of Sciences<\/a>.<\/p>\nBiologists are already able to create synthetic DNA, but the process is notoriously difficult for a certain class of phages due to their structure. DNA is built of two pairs of chemical building blocks, or base pairs, represented by the letters A, T, C, and G. The phages that attack Mycobacterium are about 65% G and C.<\/p>\n
\u201cTraditional methods of synthesizing DNA have technical problems with so-called \u2018high GC\u2019 DNA,\u201d Hatfull says, as opposed to more easily editable genomes like those of E. Coli, which have ratios of base pairs that are closer to even.<\/p>\n
To move past these obstacles, Hatfull worked with Greg Lohman of New England Biolabs, a company known for techniques enabling the design and assembly of synthetic DNA. Also integral to the work was Ansa Biotech, which has developed a process that overcomes the hurdles of synthesizing high GC DNA. The paper\u2019s first author, Ching-Chung Ko, is a research associate in Hatfull\u2019s lab.<\/p>\n
The team was able to chemically synthesize DNA identical to two naturally occurring phages: BPs\u2014a 40,000-base-pair virus used clinically to treat a bacteria that often infects people with cystic fibrosis\u2014and Bxb1, which has 50,000 base pairs. They constructed the DNA in 12 sections and inserted them into a cell, which followed the instructions from its new genome: make phages.<\/p>\n
Researchers and clinicians have become increasingly interested in phages as a response to fighting antibiotic-resistant bacterial infections. For perhaps as long as three billion years, phages and bacteria have evolved alongside one another, resulting in niches not unlike Darwin\u2019s finches; one phage will only attack one specific kind of bacteria.<\/p>\n
Exactly how phage genomes codify these relationships remains mostly a mystery.<\/p>\n
Hatfull\u2019s lab has freezers full of 28,000 phages that were found in dirt, ponds or even on rotting fruits. Finding one that will attack any particular strain of bacteria is a process of directed trial and error. When a clinician sends a sample from a sick patient, researchers use their experience, their library of about 5,500 phage genomes and plenty of petri dishes to search for a match tailored specifically to that patient.<\/p>\n
Precisely altering phage genomes and observing how those changes affect behavior will be a game-changer that will both inform researchers\u2019 understanding of how the phages work and, later, may allow them to engineer phages with broader applications.<\/p>\n
\u201cWe\u2019ve been surrounded by questions that we can\u2019t always answer because we didn\u2019t have the technologies to be able to do so,\u201d Hatfull says. \u201cThis is a technological advance that enables us in principle to begin to answer many questions in a much simpler way than we could have done before.\u201d<\/p>\n
In addition, the ability to create entirely synthetic genomes will alleviate the need to keep tens of thousands of phages on ice, with duplicates of some, and sufficient backup power sources. Instead of storing biology, Hatfull hopes one day phages can be stored simply as information.<\/p>\n
\u201cAnd then, the sky\u2019s the limit,\u201d Hatfull says. \u201cYou can make any genome you want. You\u2019re only limited by what you can imagine would be useful and interesting to make.\u201d<\/p>\n
Source: University of Pittsburgh<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"Share this Article You are free to share this article under the Attribution 4.0 International license. A new…\n","protected":false},"author":2,"featured_media":218900,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[78],"tags":[1669,18,135,19,17,1670],"class_list":{"0":"post-218899","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-bacteria","9":"tag-eire","10":"tag-health","11":"tag-ie","12":"tag-ireland","13":"tag-viruses"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@ie\/115673943507566442","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/218899","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/comments?post=218899"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/posts\/218899\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media\/218900"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/media?parent=218899"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/categories?post=218899"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/ie\/wp-json\/wp\/v2\/tags?post=218899"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}