SURF 2018: Integrase-based genetic circuits - Revision history

Ashur at 02:02, 14 December 2017

2017-12-14T02:02:59Z

← Older revision		Revision as of 02:02, 14 December 2017
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	'''Integrase-based continuous event logging'''		'''Integrase-based continuous event logging'''
			[[File:ASS_DNAPEN.jpg\|thumb\|Schematic diagram of integrase-based continuous event logger circuit. Incoming stimuli direct the recording circuit to insert an ink plasmid corresponding to the stimulus being recorded, at the end of a "DNA tape" where previously detected stimuli have been recorded.]]

	Biological records of events are omnipresent in paleontology, history, and climate science. Tree rings and ice cores provide evidence of environmental conditions that have been recorded in the composition of living cells that are deposited over time, carrying with them the a record of events that have influenced their lives before being buried underneath ice or inside the trunk of a tree. Using integrases, customizable biological memory devices can be made to record any event that a bacterium can detect. Bacteria can be unobtrusively seeded in a natural environment, providing a stable genetic record on any timescale that is suitable to the researcher.		Biological records of events are omnipresent in paleontology, history, and climate science. Tree rings and ice cores provide evidence of environmental conditions that have been recorded in the composition of living cells that are deposited over time, carrying with them the a record of events that have influenced their lives before being buried underneath ice or inside the trunk of a tree. Using integrases, customizable biological memory devices can be made to record any event that a bacterium can detect. Bacteria can be unobtrusively seeded in a natural environment, providing a stable genetic record on any timescale that is suitable to the researcher.

Ashur at 01:41, 14 December 2017

2017-12-14T01:41:22Z

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 * Co-mentor: Andrey Shur
-Integrases are bacteriophage proteins that catalyze recombination of phage DNA with the bacterial genome at specific DNA sequences known as attachment (att) sites. Serine integrases in particular can catalyze directional recombination between cognate att sites without additional cofactors and therefore are valuable tools in synthetic biology. Previous work has utilized serine integrases to construct genetic memory, logic gates, and event detectors.
+Integrases are bacteriophage proteins that catalyze recombination of phage DNA with the bacterial genome at specific DNA sequences known as attachment (att) sites. Serine integrases in particular catalyze directional recombination between cognate att sites without additional cofactors and therefore are valuable tools in synthetic biology. Previous work has utilized serine integrases and attachment sites as black boxes that inducibly flip or excise DNA to construct genetic memory, logic gates, and event detectors. We recognize that the ability to induce DNA changes can be a powerful tool in synthetic biology, since DNA is an easily tractable medium for information storage and of course encodes all the proteins and genes needed for life. Thus we are interested in expanding the list of different "functions" that integrases can perform as well as thinking about new and interesting ways to utilize the functions that are already known. A few descriptions of ongoing projects in this area are below.
-We are interested in investigating new ways to use integrases for constructing circuits and building new circuits using integrases. Examples of work in this area include developing a method to "repress" att sites using dCas9, testing the limits of att site linear spacing, and constructing a "genetic tape recorder" that can make a chronological record of events in DNA.
+'''Integrase-based continuous event logging'''
 '''References'''

Ashur: Created page with "'''2018 SURF project description''' * Mentor: Richard Murray * Co-mentor: Andrey Shur Integrases are bacteriophage proteins that catalyze recombination of phage..."

2017-12-06T19:29:18Z

Created page with "'''2018 SURF project description''' * Mentor: Richard Murray * Co-mentor: Andrey Shur Integrases are bacteriophage proteins that catalyze recombination of phage..."

New page

'''[[SURF 2018|2018 SURF]] project description'''
* Mentor: Richard Murray
* Co-mentor: Andrey Shur

Integrases are bacteriophage proteins that catalyze recombination of phage DNA with the bacterial genome at specific DNA sequences known as attachment (att) sites. Serine integrases in particular can catalyze directional recombination between cognate att sites without additional cofactors and therefore are valuable tools in synthetic biology. Previous work has utilized serine integrases to construct genetic memory, logic gates, and event detectors.

We are interested in investigating new ways to use integrases for constructing circuits and building new circuits using integrases. Examples of work in this area include developing a method to "repress" att sites using dCas9, testing the limits of att site linear spacing, and constructing a "genetic tape recorder" that can make a chronological record of events in DNA.

'''References'''
# Bonnet, J., Subsoontorn, P. & Endy, D. [http://www.pnas.org/content/109/23/8884.full Rewritable digital data storage in live cells via engineered control of recombination directionality]. Proc. Natl. Acad. Sci. 109, 8884–8889 (2012).
# Roquet, N., Soleimany, A. P., Ferris, A. C., Aaronson, S. & Lu, T. K. [http://science.sciencemag.org/content/353/6297/aad8559.full Synthetic recombinase-based state machines in living cells]. Science (80-. ). 353, aad8559-aad8559 (2016).
# Hsiao, V., Hori, Y., Rothemund, P. W. K. & Murray, R. M. [http://onlinelibrary.wiley.com/doi/10.15252/msb.20156663/full A population-based temporal logic gate for timing and recording chemical events]. Mol. Syst. Biol. 557, 1–17 (2016).
# Smith, M. C. A., Till, R. & Smith, M. C. M. [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2003.03942.x/full Switching the polarity of a bacteriophage integration system]. Mol. Microbiol. 51, 1719–1728 (2004).
# Shur, A. & Murray, R. M. [https://www.biorxiv.org/content/early/2017/02/21/110254 Repressing Integrase attachment site operation with CRISPR-Cas9 in E. coli]. bioRxiv (2017). doi:10.1101/110254
# Shur, A. & Murray, R. M. [https://www.biorxiv.org/content/biorxiv/early/2017/11/25/225151.full.pdf Proof of concept continuous event logging in living cells]. bioRxiv (2017). doi:10.1101/225151