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| ==Biography==
| | I am a graduate student in [[Knight | Tom Knight's lab]] and co-advised by [[Drew Endy]]. |
| Ph.D. Candidate in [http://web.mit.edu/be Biological Engineering] at [http://web.mit.edu MIT]. I am advised by [[User:Tk|Tom Knight]] and [[User:Endy | Drew Endy]].
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| B.S. in [http://www.cs.utah.edu/ Computer Science] from the [http://www.utah.edu/ University of Utah], 2002.
| | ==Science== |
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| ==Contact information== | | ===Education=== |
| Reshma Shetty<br>
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| MIT CSAIL<br>
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| 32 Vassar Street, Room 32-311<br>
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| Cambridge, MA 02139<br>
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| USA<br>
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| 617.253.5814<br>
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| rshetty AT mit DOT edu
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| ==Thesis research==
| | *Ph.D. candidate in [http://web.mit.edu/be Biological Engineering] at [http://web.mit.edu MIT]. |
| '''My goal is to engineer transcription-based combinational digital logic in ''Escherichia coli'' cells.'''
| | *B.S. in [http://www.cs.utah.edu/ Computer Science] from the [http://www.utah.edu/ University of Utah], 2002. |
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| Synthetic Biology seeks to intentionally design, fabricate and operate biological systems. There are three primary areas in which synthetic biological systems are of immediate utility: chemical energy, materials and information. To harness these systems to either generate new energy sources or synthesize new materials, it is necessary to develop the necessary infrastructure such that cells can be engineered to sense information, process that information using some form of logic and effect a response. Ideally, the parts and devices used to carry out information processing ''in vivo'' would have the following characteristics:
| | ===Research=== |
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| #Well-characterized: Device behavior should be quantitatively measured under standard operating conditions.
| | '''My current work is in the area of synthetic biology.''' |
| #Composable: Devices should be designed such that the output of one device can drive the input of another device. In other words, devices should be well-matched.
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| #Engineerable: It is difficult to imagine every context in which a device might be used. Therefore it is helpful if devices can be tuned such that they work well in larger systems.
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| #Numerous: Currently the size of the systems we can construct is severely limited by the lack of well-characterized devices. Therefore, it will be important to develop libraries of devices such that more complicated systems can be assembled.
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| My thesis work seeks to address these goals by developing a new type of transcription-based logic that uses modular, synthetic transcription factors. I derive the DNA binding domains of these transcription factors from zinc finger domains so that arbitrary DNA recognition sites may be used. I use leucine zippers as the dimerization domain so that these repressors are also capable of heterodimerizing increasing both the number and functionality of available dimerization domains. This implementation change adds modularity to the repressors so that domains are interchangeable and may be fine-tuned independently. Also, since there are large sets of both of these domains kinds available, this design enhances the scalability of transcription-based logic. Another key benefit of my proposed transcription-based logic is that by changing the fundamental event that occurs in the device from a single protein dimerizing on the DNA and repressing transcription to two proteins heterodimerizing on the DNA and repressing transcription, faster and more compact logic may be developed.
| | *[[Reshma Shetty/Thesis research | Thesis research]]: a brief summary of my thesis research and interests. |
| | *[http://hdl.handle.net/1721.1/29800 ICSB 2005 poster]: my latest poster on my work. |
| | *[[Reshma Shetty/FAQ and thoughts | FAQ and thoughts]]: my own answers to frequently asked questions and objections to the field as well as thoughts on related experimental issues. |
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| Some of the questions that I am interested in addressing as a part of my thesis work include the following.
| | '''Other related discussions and projects in which I am involved.''' |
| # How do you evaluate device performance? When is the performance of a device good enough? What does good enough mean?
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| # How do you engineer a device to deliver good performance?
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| # How should device behavior be characterized and quantified? How little work can we get away with and call a device characterized?
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| # How do you insulate devices from one another? How do you design them to be orthogonal? How many devices can you put inside a cell?
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| and more.
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| ==Frequently asked questions/objections==
| | *[[BioBricks]]: a one stop shop for all BioBricks related information and projects. |
| ''Disclaimer: These are personal opinions developed as a result of my own thinking on this subject and interactions with others (which I have tried to note as applicable). They are highly likely to evolve over time. If you have a comment/question on something here, send me an email.''
| | *[[Synthetic Biology:Abstraction hierarchy | Abstraction hierarchy]]: thinking about a framework within which to engineer synthetic biological systems. |
| | *[[Synthetic_Biology:Vectors/Single_copy_plasmid | Single copy BioBricks vector for characterization]]: designing a near single copy vector for characterization of BioBricks parts, devices and systems. |
| | *[[Standard_E._coli_Strain_for_BioBricks | A standard strain for BioBricks]]: specifying a standard strain in which BioBricks parts, devices and systems would work. |
| | *[[Parts characterization | Standards for parts characterization]]: thinking about what BioBricks characterization standards might look like. |
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| ===But life isn't digital!=== | | ===Teaching=== |
| The most common question I receive when talking about my work with others is "Biology isn't digital, so why concentrate on digital logic"? There's an answer on the [[SB:FAQ | Synthetic Biology FAQ]] but I'll give my own two cents here. In my mind, there are two valid responses to this question.
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| ====Maybe not, but we are better at thinking digitally.====
| | *[[BE.109]]: I am a teaching assistant for BE.109 and helping out [[Natalie Kuldell]] in the experiment of integrating BE.109 and OpenWetWare. |
| This is the answer I usually give. After thinking about this question a fair amount and talking with others in the MIT Synthetic Biology Working Group (especially Tom Knight), I came to the conclusion that the first "digital" devices in electrical engineering probably weren't very digital either. In fact, even today's devices aren't 100% digital. Calling a device "digital" is really an abstraction we place upon a physical object that behaves according to certain specifications. By carefully determining those behavior requirements and carefully engineering the device, the digital abstraction holds up sufficiently well for the device to work as desired. A lot of work has already been done in electrical engineering in terms of engineering digital circuits from analog electrical components. We should be able to leverage this expertise to design digital devices from analog, biological components.
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| ====Sure it is.==== | | ===Other=== |
| Information in biology is encoded by DNA which consists of strings of 4 kinds of nucleotides. Therefore life is fundamentally digital. I first heard this argument in a talk given by [http://www.systemsbiology.org/Scientists_and_Research/Faculty_Groups/Hood_Group Leroy Hood] at MIT in 2003 but I am sure that others use it as well. If biology at its core is digital, then it is no longer so unreasonable to design digital devices from biological parts.
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| ===BioBricks assembly is too cumbersome.===
| | '''Some non-science but still important discussions and projects in which I am participating.''' |
| Agreed. I would really like to be able to email an arbitrarily long DNA sequence to a synthesizer sitting in my lab and have it given me a tube with that DNA in it for very little cost. It would make my Ph.D. go much faster. Unfortunately, we aren't quite there yet (though some might justifiably disagree). So as a stopgap measure, BioBricks assembly allows us to construct systems from parts in a *relatively* cheap, efficient and reproducible manner.
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| However, in my mind there is a clear difference between the concept behind BioBricks itself (and by BioBricks, I am referring to the parts in the [http://parts.mit.edu MIT Registry of Standard Biological Parts]) and the method used to assemble BioBricks together. There are various ways that one could imagine to [http://www.csail.mit.edu/research/abstracts/abstracts04/html/328/328.html improve assembly] or even eliminate it all together by using DNA synthesis instead. Regardless of the technique used to fabricate a system, it is still useful to maintain a library of reusable, well-characterized biological parts from which systems can be made. This is how engineers avoid "reinventing the wheel" so to speak. In my mind, it is this concept (not the particular assembly technique) that is the key idea behind BioBricks. Thus, I think BioBricks and the Registry of Standard Biological Parts will still be useful even if/when long DNA synthesis is easily available.
| | *[[Main Page | OpenWetWare]]: a wiki for researchers in biological science and engineering to enable more sharing and collaboration in the research community. |
| | *[[Publishing Group | Publishing]]: can we improve the publishing system in synthetic biology? |
| | **To this end, I helped set up the MIT DSpace synthetic biology publishing archive. Check out the archive [https://dspace.mit.edu/handle/1721.1/18185/browse-date by date] [https://dspace.mit.edu/handle/1721.1/18185/browse-author by author] |
| | *[[Science 2.0]]: some thoughts on how the conduct of science will change through Web2.0 technologies. |
| | *[[Synthetic Society | Synthetic Society Working Group]]: a working group exploring societal issues around synthetic biology. |
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| ===What's the difference between parts, devices and systems?=== | | ===Previous research=== |
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| See the discussion on an [[Synthetic Biology:Abstraction hierarchy | abstraction hierarchy]] which initially arose from a discussion with [[Jason Kelly]] and [[Ilya Sytchev]].
| | *Prior to coming to MIT, I spent a few months in [http://www-cryst.bioc.cam.ac.uk/ Tom Blundell's lab] at the [http://www.cam.ac.uk/ University of Cambridge] working on [http://raven.bioc.cam.ac.uk/ RAPPER]. |
| | *Before that, I worked as an undergrad research assistant for several years in [http://www.biology.utah.edu/faculty2.php?inum=7 Baldmero Olivera's] lab at the [http://www.utah.edu/ University of Utah]. I worked on a few different projects during that time. More to come (maybe). |
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| ==Random musings== | | ==Contact== |
| Here's some thoughts that I decided to post. Feedback is welcome.
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| ===Diatribe on ''Escherichia coli'' strains===
| | Reshma Shetty<br> |
| One thing that surprises me is how difficult it is to find an ''Escherichia coli'' strain that meets a certain set of specifications. For instance, I want a strain with the lactose permease knocked out and the arabinose permease under the control of a constitutive promoter so that I can get linear induction with both lactose and arabinose. I don't think one exists (if it does please email me!). I also can't find a strain that is lacI<sup>q</sup> and has the lactose permease deleted (again email me if you have this strain!). I find this situation mildly frustrating.
| | MIT CSAIL<br> |
| | | 32 Vassar Street, Room 32-311<br> |
| I also find the nomenclature of ''Escherichia coli'' genotype information to be unnecessarily confusing but I am willing to let it slide as a historical artifact. (See the attempt to [[E. coli genotypes#Nomenclature & Abbreviations | decipher the code]].)
| | Cambridge, MA 02139<br> |
| | | USA<br> |
| However, in my mind what is truly astonishing is the dearth of information available on existing strains and the fact that some of this information is wrong! Case in point: I was interested in using a strain of ''Escherichia coli'' with the lacI<sup>q</sup> mutation. I found various strains that are supposed to have this mutation: [[E. coli genotypes#D1210 | D1210]], [[E. coli genotypes#JM109 | JM109]], [[E. coli genotypes#BW26434, CGSC Strain # 7658 | BW26434]]. Then, since I was getting some anomalous experimental results, Tom suggested that I sequence verify the fact that my strains were lacI<sup>q</sup>. So I did and lo and behold, none of my sequences had the lacI<sup>q</sup> mutation on the genome. Now based on my anomalous experimental results (which are no longer so anomalous) and reading of some papers, I think that [[E. coli genotypes#D1210 | D1210]] really is lacI<sup>q</sup> but that it just has lacI<sup>q</sup> on the F plasmid rather than on the genome. But [[E. coli genotypes#JM109 | JM109]] and [[E. coli genotypes#BW26434, CGSC Strain # 7658 | BW26434]] ... or at least the versions that I sequenced ... are not lacI<sup>q</sup> as documented. I don't understand how people use these strains without having correct genotype information. I also don't understand that with all the sequencing centers there are and how many people work on or with ''Escherichia coli'', why all the common lab strains at least don't get sequenced. Some claim it is a combination of the lack of resources and the fact that this isn't an interesting thing to do. Quite possibly this is true, but nevertheless, I find this situation unbelievable. Anyway, it was these experiences that led me to populate the [[Standard E. coli Strain for BioBricks | standard strain page]].
| | 617.253.5814<br> |
| | rshetty AT mit DOT edu |
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| ==Miscellaneous== | | ==Miscellaneous== |
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| *The other kind of [http://www.newscientist.com/article.ns?id=dn2731 biobricks]. | | *The other kind of [http://www.newscientist.com/article.ns?id=dn2731 biobricks]. |
| *[http://www.washingtonpost.com/wp-dyn/content/article/2005/11/11/AR2005111100674.html Google, Venter and genomics ... oh my!] | | *[http://www.washingtonpost.com/wp-dyn/content/article/2005/11/11/AR2005111100674.html Google, Venter and genomics ... oh my!] |
| *[http://www.quarter-life-crisis.com Quarter-Life-Crisis]: outlet for the artistically inclined twenty-something. | | *[http://www.quarter-life-crisis.com Quarter-Life-Crisis]: outlet for the artistically inclined twenty-something. (Shameless plug for a friend's website.) |
| | *Check out the [http://web.mit.edu/kickboxing/ MIT Kickboxing Club]. (My new hobby.) |
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| __NOTOC__ | | __NOTOC__ |
