{"id":1208,"date":"2015-09-01T03:01:02","date_gmt":"2015-09-01T03:01:02","guid":{"rendered":"http:\/\/www.kurzweilai.net\/?p=260576"},"modified":"2015-09-01T03:01:02","modified_gmt":"2015-09-01T03:01:02","slug":"engineered-bacteria-form-multicellular-circuit-to-control-protein-expression","status":"publish","type":"post","link":"https:\/\/hoo.central12.com\/fugic\/2015\/09\/01\/engineered-bacteria-form-multicellular-circuit-to-control-protein-expression\/","title":{"rendered":"Engineered bacteria form multicellular circuit to control protein expression"},"content":{"rendered":"
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Two strains of synthetically engineered bacteria cooperate to create multicellular phenomena. Their fluorescence indicates the engineered capabilities have been activated. (credit: Bennett Lab\/Rice University)<\/p><\/div>\n

Rice University<\/a> scientists and associates have\u00a0created a biological equivalent to a computer circuit using multiple types of bacteria that change protein expression. The goal is to modify biological systems by controlling how bacteria influence each other. This could lead to bacteria that, for instance, beneficially alter the\u00a0gut microbiome<\/a> (collection of microorganisms) in humans.<\/p>\n

The research is published in the journal Science<\/a><\/em>.<\/p>\n

Humans\u2019 stomachs have a lot of different kinds of bacteria contained in the microbiome. \u201cThey naturally form a large consortium,” said Rice synthetic biologist Matthew Bennett<\/a>. The idea is to engineer bacteria to be part of a consortium. “Working together allows them to effect more change than if they worked in isolation.\u201d<\/p>\n

In the proof-of-concept study, Bennett and his team created two strains of genetically engineered bacteria that regulate the production of proteins essential to intercellular\u00a0signaling pathways<\/a>, which allow cells to coordinate their efforts, generally in beneficial ways.<\/p>\n

The synthetic microbial consortium oscillator yo-yo<\/strong><\/p>\n

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The activator strain up-regulates genes in both strains; the repressor strain down-regulates genes in both strains, generating an oscillation\u00a0of gene transcription in the bacterial population (credit: Ye Chen et al.)<\/p><\/div>\n

\u201cThe main push in synthetic biology has been to engineer single cells,\u201d Bennett said. \u201cBut now we\u2019re moving toward multicellular systems. We want cells to coordinate their behaviors in order to elicit a populational response, just the way our bodies do.\u201d<\/p>\n

Bennett and his colleagues achieved their goal by engineering common Escherichia coli<\/a>\u00a0<\/em>bacteria. By creating and mixing two genetically distinct populations, they prompted the bacteria to form a consortium.<\/p>\n

The bacteria worked together by doing opposite tasks: One was an\u00a0activator<\/a>\u00a0that up-regulated the expression of targeted genes; the other was a\u00a0repressor<\/a>\u00a0that down-regulated specific genes. Together, they created oscillations of gene transcription in the bacterial population.<\/p>\n

The two novel strains of bacteria sent out intercellular signaling molecules and created linked positive and negative feedback loops that affected gene production in the entire population. Both strains were engineered to make fluorescent reporter genes so their activities could be monitored. The bacteria were confined to microfluidic devices in the lab, where they could be monitored easily during each hours-long experiment.<\/p>\n

When the bacteria were cultured in isolation, the protein oscillations did not appear, the researchers wrote.<\/p>\n

Programmed yogurt, anyone?
\n<\/strong><\/p>\n

Bennett said his lab\u2019s work will help researchers understand how cells communicate, an important factor in fighting disease. \u201cWe have many different types of cells in our bodies, from skin cells to liver cells to pancreatic cells, and they all coordinate their behaviors to make us work properly,\u201d he said. \u201cTo do this, they often send out small signaling molecules that are produced in one cell type and effect change in another cell type.<\/p>\n

\u201cWe take that principle and engineer it into these very simple organisms to see if we can understand and build multicellular systems from the ground up.\u201d<\/p>\n

Ultimately, people might ingest the equivalent of biological computers that can be programmed through one\u2019s diet, Bennett said. \u201cOne idea is to create a yogurt using engineered bacteria,\u201d he said. \u201cThe patient eats it and the physician controls the bacteria through the patient\u2019s diet. Certain combinations of molecules in your food can turn systems within the synthetic bacteria on and off, and then these systems can communicate with each other to effect change within your gut.\u201d<\/p>\n

KAIST and University of Houston scientists were also involved in the research. The National Institutes of Health, the Robert A. Welch Foundation, the Hamill Foundation, the National Science Foundation, and the China Scholarship Council supported the research.<\/p>\n

\n

Abstract of\u00a0Emergent genetic oscillations in a synthetic microbial consortium<\/em><\/strong><\/p>\n

A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types\u2014an \u201cactivator\u201d strain and a \u201crepressor\u201d strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types.<\/p>\n","protected":false},"excerpt":{"rendered":"

Rice University scientists and associates have created a biological equivalent to a computer circuit using multiple types of bacteria that change protein expression. The goal is to modify biological systems by controlling how bacteria influence each other. This could lead to bacteria that, for instance, beneficially alter the gut microbiome (collection of microorganisms) in humans. The research […]<\/p>\n","protected":false},"author":13,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,47,43,267],"tags":[],"class_list":["post-1208","post","type-post","status-publish","format-standard","hentry","category-biotech","category-computersinfotechui","category-news","category-synthetic-biology"],"_links":{"self":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/1208"}],"collection":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/users\/13"}],"replies":[{"embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/comments?post=1208"}],"version-history":[{"count":1,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/1208\/revisions"}],"predecessor-version":[{"id":1209,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/posts\/1208\/revisions\/1209"}],"wp:attachment":[{"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/media?parent=1208"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/categories?post=1208"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/hoo.central12.com\/fugic\/wp-json\/wp\/v2\/tags?post=1208"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}