Biochemistry 19

Bioengineering a Nose
changing yeast DNA so that yeast cells change color when smelling explosives


In recent years humans have learned how detector molecules in neurons in our noses chemically detect odors.  The detector proteins initiative a combination of additional chemical reactions, flows of ions through flood gates spanning the neuron membrane and an accompanying electrical Voltage spike.  This electrical/chemical wave carries the signal along the surface of the long nerve axon to synapses in the brain where the information is processed, recorded, and sometimes responded to.  (See investigations Touch & Hearing, Tasting & Smelling, Pain, Nerve Messaging, Contact by Nerve, Brain Chemistry and Memories for process details.)

Human noses aren't very sensitive compared to other creatures.  So after the terrorist attacks on 9/11, dogs were trained to detect the faint odor of vapors from explosive compounds.  But the process of training and using dogs to detect explosives remains relatively expensive.  So Danny N. Dhanasekaran and his colleagues at Temple University set out to develop cheaper detectors: yeast cells.

cAMPFirst they tried to modify yeast so it had the chemistry of a nerve cell.  So the team transplanted into the yeast DNA the portions of rat DNA which produce the large proteins embedded in the nerve membranes which perform key processes in rat noses.  In a five-year effort, Dhanasekaran's team engineered into yeast the ability to manufacture 7 rat proteins required for sensing and producing a biochemical signal after exposure to an odor molecule.  One of the small molecules released in abundance by these large neuron proteins when they detect an odor is cyclic adenosine monophosphate (cAMP, the DNA nucleotide often labeled as A, shown at left, contains the adenine also in ATP, the sugar ribose, but with only one phosphate group attached as the ring at the lower left).

Next they searched for a way that the yeast could communicate when they had detected a particular molecule.  Activating the rat olfactory system leads to marked increased cellular levels of cyclic adenosine monophosphate (cAMP).  So the researchers genetically engineered the yeast to make a green fluorescent protein whenever the cAMP concentration increased.

green yeastThe final major challenge was to figure out a way to make the yeast cells detect the odor molecule.  Once the yeast's transplanted olfaction system was working, the researchers screened 1,000 rat olfactory receptor proteins to find one that could specifically detect an explosive.  They found a rat receptor protein which detects 2,4-dinitrotoluene (DNT), a byproduct of the manufacture of explosives with usually accompanies the explosive TNT, trinitrotoluene.  They spliced the DNA segment for the DNT-detecting protein into the existing olfactory system in the yeast to complete the sensor.  So when the yeast smells the TNT-associated compound, the cell makes cAMP and then turns a fluorescent green.

While this is not yet a perfected detection system, it overcomes the major challenges and demonstrates how simple organisms can be bioengineered to perform tasks where society has identified a need.  Potential applications range from diagnosing pathologies associated with odors in body fluids of sick people to monitoring environmental or industrial processes.  For this immediate task, the researchers still need to improve the yeast's sensitivity and specificity for odors in order for it to achieve its full potential.


A critical part of bioengineering is to determine what is desired, and the stepwise processes needed to achieve the desired end result.

  1. Consider an effort similar to the one described above to develop a sensor system for a new or modified purpose.
    1. What do you want to detect? (e.g., to protect people with fatal peanut allergies, say you wish to detect peanut fragments in foods )
    2. What are the properties of the information you wish to detect? (e.g., do peanut fragments release vapors or respond uniquely to certain light or sound?)
    3. What restrictions do those properties impose on a detection system? (e.g., if peanuts emit a particular light pattern under certain conditions, what would create those conditions?)
    4. What system would be appropriate to modify to do the detection? (e.g., what would be necessary to detect and distinguish the peanut light pattern?)

  2. Before something different or better is developed, it is appropriate to understand that which already exists.  Review the mechanism used by a nervous system to detect aspects of its environment and transmit a message of that information.  It may be helpful to review earlier experiments and make an outline of the various mechanisms used by neurons:  Touch & Hearing, Tasting & Smelling, Pain, Nerve Messaging, Contact by Nerve and Brain Chemistry.  While a biological system might work, also consider if other physical or chemical systems might work better.

  3. Consider each step in the mechanism chosen as the basis for the new sensor.  Determine if that portion of the mechanism will serve the purpose or need change.  Determine the details for each required change.

  4. Map out steps which should be accomplished to make the changes and adaptations necessary to make you sensor system function.

  5. Consider if this procedure is adequate, or whether the procedure itself needs modification.

If you need course credit, use your notes recorded in your journal to construct a formal report.


Yeast Sniffs Out Explosives, Chemical & Engineering News, Vol 85 # 20, 14 May 2007


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created 19 May 2007
revised 27 March 2008
by D Trapp
Mac made