Team:Stanford/Research

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Our Project: Two Designs for Ratio Detection

Our team decided to pursue two different systems for detecting ratios. While both systems receive two input signals, the output they give is different, allowing them be applied in different situations. Here's a brief rundown of the two designs (you can see more by clicking through to the individual project pages).

The First Sensor:

Method: Small RNA Interference

Output: One of two possible proteins, depending on whether the ratio of input chemicals lies above or below a predetermined threshold

Useful: For reporting on a situation with a boolean output: disease detection, preterm labor warning, cancer metastasis warning


The Second Sensor:

Method: Kinase/Phosphatase Regulation of a Transcription Factor

Output: One output protein whose concentration is linearly dependent on the ratio of the input chemicals

Useful: For acting in a situation requiring a graded response: drug delivery, metabolic flux control, detailed ratiometric reporting


Both sensors are:

  • Modular: input and output molecules can be changed without affecting the interior mechanism of the device
  • Orthogonal: device mechanisms are not found in E. coli, avoid crosstalk with host cell

Ratios: Better than Absolutes

Why did we go to the trouble of developing sensors to detect ratios when so many already exist to detect absolute concentrations? Because ratios are better.

For many biological processes, absolute concentrations vary with time or environmental conditions. A sensor detecting the absolute concentration of a biologically significant molecule would respond to these fluctuations, creating systemic noise and false results. Our sensors can detect a "normalized" version of the molecule's concentration by comparing it to a different molecule whose regular cycles are similar.

Our unified sensor is also better than simply combining two absolute sensors into a single cell and comparing the outputs. Besides requiring the cell to produce fewer proteins (freeing up cell energy for other processes), our approach significantly reduces output noise. Additionally, a two-output system requires a human observer to take readings and make a decision. Our system can be hooked up straight to an output protein, allowing a rapid in-vivo response.


Research


Medal Requirements

Bronze Medal

  1. Register the team, have a great summer, and have fun attending the Jamboree.
    Done!
  2. Successfully complete and submit a Project Summary form.
    Done!
  3. Create and share a Description of the team's project via the iGEM wiki
    Done!
  4. Present a Poster and Talk at the iGEM Jamboree
    Booked our plane tickets!
  5. Enter information detailing at least one new standard BioBrick Part or Device in the Registry of Parts
    Done?
  6. Entered information for each new part or device should at least include primary nucleic acid sequence, description of function, authorship, any relevant safety notes, and an acknowledgement of sources and references.
    Done?
  7. Submit DNA for at least one new BioBrick Part or Device to the Registry of Parts.
    Done?

Silver Medal

  1. Demonstrate that at least one new BioBrick Part or Device of your own design and construction works as expected.
    Waiting for lab results...
  2. Characterize the operation of at least one new BioBrick Part or Device and enter this information on the Parts or Device page via the Registry of Parts
    Waiting for lab results...

Gold Medal

  1. Characterize or improve an existing BioBrick Part or Device and enter this information back on the Registry.
    When sequencing one of our ligations, we noticed an unexpected sequence in our results. After more investigation, we determined that that sequence came from the Distribution part [http://partsregistry.org/wiki/index.php?title=Part:BBa_E1010 BBa_E1010], and that the part sequence listed on the Parts Registry was incomplete.
  2. Help another iGEM team by, for example, characterizing a part, debugging a construct, or modeling or simulating their system.
    With our Twitter project, we hope to help all iGEM teams by facilitating collaboration between teams. Read more about it here!




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