User:Reshma P. Shetty: Difference between revisions

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==Biography==
[[Image:ReshmaShettyPhoto.jpg|right|thumb]]
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]].


B.S. in [http://www.cs.utah.edu/ Computer Science] from the [http://www.utah.edu/ University of Utah], 2002.
I am a co-founder of [http://ginkgobioworks.com Ginkgo BioWorks, Inc.].


==Contact information==
===Education===
Reshma Shetty<br>
 
MIT CSAIL<br>
*Ph.D. in [http://web.mit.edu/be Biological Engineering] from [http://web.mit.edu MIT], 2008.
32 Vassar Street, Room 32-311<br>
*B.S. in [http://www.cs.utah.edu/ Computer Science] from the [http://www.utah.edu/ University of Utah], 2002.
Cambridge, MA 02139<br>
USA<br>
617.253.5814<br>
rshetty AT mit DOT edu


==Thesis research==
===Current research===
'''My goal is to engineer transcription-based combinational digital logic in ''Escherichia coli'' cells.'''


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:
'''My current work is in the area of synthetic biology.'''


#Well-characterized: Device behavior should be quantitatively measured under standard operating conditions.
*[http://hdl.handle.net/1721.1/41843 Applying engineering principles to the design and construction of transcriptional devices] (Ph.D. thesis)
#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.
*[[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.
#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.
#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.


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.
'''Other related discussions and projects in which I am involved.'''


Some of the questions that I am interested in addressing as a part of my thesis work include the following.
*[[BioBricks]]: a one stop shop for all BioBricks related information and projects.
# How do you evaluate device performance?  When is the performance of a device good enough?  What does good enough mean?
*[[Synthetic Biology:Abstraction hierarchy | Abstraction hierarchy]]: thinking about a framework within which to engineer synthetic biological systems.
# How do you engineer a device to deliver good performance?
*[[Synthetic Biology:Vectors/pSB**5 design | A new BioBricks vector design]]: designing a new, extensible BioBricks vector scaffold.
# How should device behavior be characterized and quantified?  How little work can we get away with and call a device characterized?
*[[Standard_E._coli_Strain_for_BioBricks | A standard strain for BioBricks]]: specifying a standard strain in which BioBricks parts, devices and systems would operate.
# 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?
*[[Parts characterization | Standards for parts characterization]]: thinking about what BioBricks characterization standards might look like.
and more.
*[[Synthetic Biology:Vectors/Barcode | Barcodes for synthetic biological systems]]


==Frequently asked questions/objections==
===Teaching===
''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.''


===But life isn't digital!===
*[[iGEM:MIT/2006|MIT iGEM]]: I served as an advisor to the 2006 MIT iGEM team.  (iGEM is an acronym for international Genetically Engineering Machines competition.)  The team won [http://igem2006.com/results.htm "Best System"] for engineering bacteria to smell like wintergreen and banana over the course of a single summer.  
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.
*[[BE.109|BE.109: Laboratory fundamentals of biological engineering]]: I was a teaching assistant for BE.109 in Spring 2006.  [[Natalie Kuldell]] and I experimented with the integration of BE.109 and OpenWetWare.
*[http://stellar.mit.edu/S/course/7/sp04/7.91/index.html BE.490: Foundations of Computational & Systems Biology]: In Spring 2004, I was a teaching assistant for BE.490.


====Maybe not, but we are better at thinking digitally.====
===Previous research===
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.


====Sure it is.====
*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]: ''ab initio'' conformational search algorithm for restraint-based protein structure modeling.
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.
*Before that, I worked as an undergrad research assistant for several years in [http://www.biology.utah.edu/faculty2.php?inum=7 Baldomero Olivera's] lab at the [http://www.utah.edu/ University of Utah].  I worked on a few different projects during that time including the identification of the post-translational modification enzyme &gamma;-glutamyl carboxylase in ''Conus'' and ''Drosophila''.  Also, I helped to discover two novel superfamilies of neurotoxins from the venom of the molluscs ''Conus''.


===BioBricks assembly is too cumbersome.===
See [[Reshma Shetty/Publications | my publications]].
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.


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.
===Honors===


===What's the difference between parts, devices and systems?===
*National Science Foundation Graduate Research Fellowship, 2005-2007.
*Whitaker Graduate Fellowship in Biomedical Engineering, 2002-2004.
*Andrew and Edna Viterbi Fellowship in Computational Biology, 2002-2003.


See these [[BioBricks abstraction hierarchy | notes]] from a discussion with [[Jason Kelly]] and [[Ilya Sytchev]].
===Activities===


==Random musings==
'''Some non-research but still important discussions and projects in which I am participating.'''
Here's some thoughts that I decided to post.  Feedback is welcome.


===Diatribe on ''Escherichia coli'' strains===
*[[Main Page | OpenWetWare]]: a wiki for researchers in biological science and engineering to enable more sharing and collaboration in the research community.  I serve on the [[OpenWetWare steering committee]].  Here are [[Special:Contributions/Rshetty | my contributions]] to the site.
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.
*[http://igem2006.com iGEM]: I served as a part-time iGEM 2006 ambassador to Asia.
*[[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]
*[[Synthetic Society | Synthetic Society Working Group]]: a working group exploring societal issues around synthetic biology.
*Previously, I also helped to organize [http://syntheticbiology.org/Synthetic_Biology_1.0.html Synthetic Biology 1.0]: The First International Meeting on Synthetic Biology.


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]].)
===Contact===


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]]. 
Reshma Shetty<br>
rshetty AT ginkgobioworks DOT com


==Miscellaneous==
===Bookmarks===
<font size=2>
<xfeeds titlecolour="#e5edc8" notimestamp="Y" contentcolour="#e5edc8" feedlimit="10" totallimit="20">
http://del.icio.us/rss/rpshetty/research
</xfeeds>
</font>


===Miscellaneous===
*[[Reshma Shetty/blog]] <-- trying out a blog
*[http://science.slashdot.org/science/06/11/06/1913228.shtml We made Slashdot!]
*[http://money.cnn.com/ CNN Money] has an [http://money.cnn.com/2005/08/15/pf/training_pay/index.htm article] called "Big jobs that pay badly."  The three examples they cite: architect, chef and academic research scientist.
*[http://money.cnn.com/ CNN Money] has an [http://money.cnn.com/2005/08/15/pf/training_pay/index.htm article] called "Big jobs that pay badly."  The three examples they cite: architect, chef and academic research scientist.
*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.quarter-life-crisis.com Quarter-Life-Crisis]: outlet for the artistically inclined twenty-something. (Shameless plug for a friend's website.)
*The [http://aimediaserver.com/studiodaily/videoplayer/?src=harvard/harvard.swf&width=640&height=520 Mechanome]


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[[Category:Steering Committee member]]

Latest revision as of 22:04, 25 October 2008

I am a co-founder of Ginkgo BioWorks, Inc..

Education

Current research

My current work is in the area of synthetic biology.

Other related discussions and projects in which I am involved.

Teaching

Previous research

  • Prior to coming to MIT, I spent a few months in Tom Blundell's lab at the University of Cambridge working on RAPPER: ab initio conformational search algorithm for restraint-based protein structure modeling.
  • Before that, I worked as an undergrad research assistant for several years in Baldomero Olivera's lab at the University of Utah. I worked on a few different projects during that time including the identification of the post-translational modification enzyme γ-glutamyl carboxylase in Conus and Drosophila. Also, I helped to discover two novel superfamilies of neurotoxins from the venom of the molluscs Conus.

See my publications.

Honors

  • National Science Foundation Graduate Research Fellowship, 2005-2007.
  • Whitaker Graduate Fellowship in Biomedical Engineering, 2002-2004.
  • Andrew and Edna Viterbi Fellowship in Computational Biology, 2002-2003.

Activities

Some non-research but still important discussions and projects in which I am participating.

Contact

Reshma Shetty
rshetty AT ginkgobioworks DOT com

Bookmarks

<xfeeds titlecolour="#e5edc8" notimestamp="Y" contentcolour="#e5edc8" feedlimit="10" totallimit="20"> http://del.icio.us/rss/rpshetty/research </xfeeds>

Miscellaneous

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