Biomod/2013/Harvard/introduction

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Introduction

easy applications

The importance of being able to detect of bioagents pervades our daily lives as it plays an essential role in biotechnology, medicine, agriculture, and even in military. For example, glucose monitoring for diabetes, fighting bioterrorism, screening for food toxins, and diagnosing a disease all require an efficient method of detecting bioagents.



Biosensors and Allosteric Switches

One approach for detecting bioagents is the use of biosensors. Biosensors are biologically derived chemical sensing device that recognizes a presence of a certain molecule and outputs a measurable signal in response. It is composed of two parts: the bio-element that recognizes a specific analyte, or bioagent, and the transducer that converts the recognition into a readily detectable output signal.

A Biosensor Enzyme (Adapted from   Mohanty et al, 2006)
A Biosensor Enzyme (Adapted from Mohanty et al, 2006)

Proteins often function as sensors and monitors in nature, and are therefore often used as platforms for engineered biosensors. Many proteins show drastic alterations in conformation or function in response to the presence of another molecule, and thus already act as basic biosensors. These natural responses can be harnessed to create a man-made sensor that is biologically emulative. Standard protein mechanics, such as a change in formation upon ligand binding, can be modified to occur in response to novel events or conditions. The advantage of using these pre-existing biological system is that there are many, many methods of molecule detection and response already in existence. Natural proteins have evolved to exhibit efficient enzymatic activity and specific binding that would be difficult to engineer de novo. Natural systems provide excellent starting points for biosensor design, but elements must be altered or substituted to produce novel functionality. In the case of proteins, either the sensitivity and affinity for other molecules, the "input," or the protein's subsequent response to such molecules, the "output," is engineered toward the desired sensor behavior. On the input side, there are thousands of important small molecules, peptides, and larger proteins that are known to cause a conformational change or other detectable response in a protein upon binding. Thus, there are a multitude of proteins capable of sensing molecules already existent in nature. The output response of these proteins is equally varied, but certain enzymatic outputs are particularly useful to researchers.

Image:Camconformationchange.png
Protein conformational change after molecule binding
For example, proteins that produce a luminescent or fluorescent output allow the presence of their analyte to be visually observed. Most proteins do not produce a readily observed output though, so they must be augmented or combined to produce a viable sensor. The ideal protein biosensor would be easily modifiable on both the input and output end, allowing easy customization of what the protein senses, and how it reports its sensing. Such a modular protein-based biosensor would have many advantages. First, it would make use of naturally existing activity that can recognize molecules and then deliver an easily detectable signal via an enzymatic response. Secondly, it could be straightforwardly redesigned to sense new compounds and report through a variety mechanisms. Proteins possess a natural ability to detect and respond to other compounds, making them important scaffolds for biosensor development. As our entry to the BioMOD 2013 competition, we worked to demonstrate the power of protein-based biosensors through the creation of a modular sensor.
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