MIT 20 109 Module 1 Class 3 notes DRAFT 18 September 2007 Genome Engineering Drew Endy http mit edu endy Questions Introduced Last Time D What is a standard biological part E What is reliable physical composition And reliable functional composition F How does synthetic biology relate to genetic engineering Discussion for Today F How does synthetic biology relate to genetic engineering G Can we implement reliable physical and functional composition via standard biological parts ANNOUNCEMENT Genetic control of the synthesis and assembly of materials for electronics and energy Angela Belcher Mass Tech 4 5p today in 32 123 food at 3 40p outside room 34 How does synthetic biology relate to genetic engineering People have long been interested in using biology to solve problems from food and shelter to drug production and biofuels and now a wider number of applications includ ing building electronics environmental monitoring and remediation and perhaps even growing large scale structures like houses About 30 years ago researchers discov ered restriction endonucleases and invented recombinant DNA technology rDNA rDNA allows people to intentionally cut and paste pre existing fragments of genetic ma terial so long as the restriction sites are in the right places This marked the begin ning of genetic engineering What does it mean to be an engineer 35 About the same time the rDNA technology got invented polymerase chain reaction PCR was gured out with some of the foundational work being done here at MIT and then fully invented in the 1980s at Cetus Inc As important by 1977 DNA sequencing was gured out by Fred Sanger at Harvard Cite as Drew Endy Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY MIT 20 109 Module 1 Class 3 notes DRAFT 18 September 2007 36 Taken together rDNA PCR and DNA sequencing form a core set of underlying technologies that allow for the editing and reading out of genetic material Since bio logical systems are encoded via genetic material these are important technologies both biological science e g change things and see what happens and biological engineer ing e g make something that does what you want hopefully For whatever reasons these three technologies form the basis of what has been called genetic engi neering It doesn t really matter what you call it so long as you appreciate what the technologies can do and how to use them for constructive purposes 37 One important lesson across all of engineering is that so much as it is possi ble it is critically important to improve the tools that we use to solve problems Building 32 was designed with computers using computer aided design CAD software adapted from plane manufacture For that matter the Boeing 777 was designed entirely on computer so I am told Microprocessors can only be designed using CAD tools de veloped back in the 1970s And let s not forget the American System of Manufacturing developed in Western Mass and other places back in the early to mid 1800s for pro ducing guns So as a question could we get better at reading DNA i e sequenc ing And could we get better at writing DNA i e synthesis or construction 38 The answer to this question is obviously yes So today there are three new technologies being developed that aid in the process of engineering biological systems These three technologies are a automated DNA construction b physical and functional composition and other standards and c abstraction Automated DNA construction based on DNA synthesis lets us make DNA from scratch in place of bashing DNA together in the lab w rDNA and PCR Standards and abstrac tion help us manage the information going into the DNA synthesizers Taken together these three new technologies extend and improve the underlying foundations of both biological science and engineering For whatever reasons these three new technolo gies form the basis of what is now being called synthetic biology Again it doesn t really matter to me what you call it so long as you know what is going on and why And as a nal comment just like DNA sequencing and PCR and rDNA technology was fairly primitive in 1977 compared to today many aspects of these three new foun dational technologies are immature We have to go make them happen if we want make biology easier to engineer functional and physical composition 39 As one example of functional composition b c of 20 109 lab here s a quick link to the paper http www pnas org cgi content abstract 104 36 14283 Cite as Drew Endy Course materials for 20 109 Laboratory Fundamentals in Biological Engineering Fall 2007 MIT OpenCourseWare http ocw mit edu Massachusetts Institute of Technology Downloaded on DD Month YYYY MIT 20 109 Module 1 Class 3 notes DRAFT 18 September 2007 Basically a riboswitch is made from three parts A ribozyme an aptamer and a com munication domain A ribozyme is an RNA structure that has an enzymatic activity it can cut RNA usually itself An aptamer is an RNA structure that can interact with an other chemical e g a small molecule like caffeine A communication domain links the ribozyme and the aptamer together so that when the ligand and present the ribozyme is either activated or inactivated 40 The key advance in this engineered riboswitch work appears to be that the authors have gured out how to combine any aptamer with a ribozyme in order to control ribo zyme activity although they have only shown that two different aptamers work what could be some of the problems that might come up They ve also gure out how to in tegrate their riboswitches into transcripts in order to control gene expression and claim to be able to control the level of most any mRNA So this work is an example of reli able functional composition Because functional composition appears to be working you could be switches against most anything you can nd an aptamer for Question Do these authors present any results on reliable physical compo sition Not that I can see 41 Now as an example of physical composition Let s take a look at the parts in the Registry of Standard Biological Parts note that it is not called the Registry of Biological Parts so there must be something different about Standard Biological Parts right It turns out that the parts currently in the Registry are called BioBrick parts one brand of standard biological parts although there are not yet any competing brands of standard